Benzoyl chloride [BzCl] by Asch

Query Query

Results

Date

294 reactions in Reaxys

2016-07-02 05h:01m:00s (EST)

294 reactions in Reaxys

2016-07-02 05h:05m:25s (EST)

1. Query

Search as: As drawn, No mixtures, No charges, No radicals 2. Query

(1. Query) AND NOT itemno in (6,11,12,14,15,16,19,20,21,22,23,28,29,30,31,32,33,34,35,36,37, 38,39,40,41,42,43,44,45,46,47,48,51,52,53,54,55,58)

1/118

2016-07-02 05:35:12

Cl Cl

Rx-ID: 666322 View in Reaxys 1/294 Yield 89%

Conditions & References 2 : EXAMPLE 2. Benzotrichloride (2.0 tons) and FeCl3 (7.1 kg) are slowly, at 150° to 160° C., to the mixture obtained by chlorination of 6.2 tons of distilled residue to convert the benzoic acid and any benzoic acid anhydride present into benzoyl chloride. After the evolution of HCl gas has ended, a vacuum distillation is carried out. Pure benzoyl chloride is obtained in this distillation (7.3 tons). The yield is about 89percent. With FeCl3 Patent; Bayer Aktiengesellschaft; US4430181; (1984); (A1) English View in Reaxys With massicot Hoffmann; Meyer,V.; Chemische Berichte; vol. 25; (1892); p. 212 View in Reaxys With zinc oxide Hoffmann; Meyer,V.; Chemische Berichte; vol. 25; (1892); p. 212 View in Reaxys With zinc oxide, T= 100 °C Davies; Dick; Journal of the Chemical Society; (1932); p. 2808 View in Reaxys With vanadium pentoxide Patent; Du Pont de Nemours and Co.; US2856425; (1956) View in Reaxys With water, iron(III) chloride, T= 100 °C Patent; BASF; DE331696; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 272 View in Reaxys With chloroacetic acid, zinc(II) chloride, T= 80 - 90 °C Rabcewicz-Zubkowski; Roczniki Chemii; vol. 9; p. 526; Chem. Zentralbl.; vol. 100; nb. II; (1929); p. 2767 View in Reaxys With steam, Leiten ueber Zinnphosphat/Bimsstein bei 240grad Abkin; Medwedew; ; vol. 11; nb. 1; (1934); p. 30,33; Chem. Zentralbl.; vol. 106; nb. I; (1935); p. 2801 View in Reaxys With benzophenone, antimony(V) pentachloride, 1.) CH2Cl2, -50 deg C, 2.) CH2Cl2, 23 deg C, 24 h, Yield given. Multistep reaction Hamed, Atef; Mueller, Edgar; Al-Talib, Mahmoud; Jochims, Johannes C.; Synthesis; nb. 8; (1987); p. 745 - 748 View in Reaxys 3 : EXAMPLE 3 According to distillation analysis, the crude product contains 6.0percent by weight of benzoic acid and benzoic anhydride. Continuous distillation of the crude product under 50 mbars gives, per hour, 1,198 g of pure, benzotrichloride-free benzoyl chloride and 172 g of distillation bottom product.

2/118

2016-07-02 05:35:12

The amount of distillation bottom product obtained in 12 hours (2,064 g) is heated with 2,718 g of benzotrichloride to 150° C. in a stirred vessel fitted with a reflux condenser and the mixture is kept at this temperature for 2 hours. Distillation under 50 mbars gives 4,140 g of a mixture of benzotrichloride and benzoyl chloride with a benzotrichloride content of 22.6percent by weight of this mixture is metered back into the first vessel of the four-stage cascade. With benzoic acid Patent; Bayer Aktiengesellschaft; US4276231; (1981); (A1) English View in Reaxys 1 : EXAMPLE 1. 2,000 g of the chlorination mixture was reacted with benzotrichloride (520 g) and FeCl3 (1.9 g) at 150° C. to convert benzoic acid into benzoyl chloride. After the evolution of HCl gas has ended, the mixture is fractionally distilled in vacuo. 1,890 g of pure benzoyl chloride are obtained in this procedure (approx. 90percent yield). With FeCl3 Patent; Bayer Aktiengesellschaft; US4430181; (1984); (A1) English View in Reaxys 3 : EXAMPLE 3 EXAMPLE 3 586.5 g (3 mols) of benzotrichloride and 722 g (6 mols) of benzoic acid were weighed out into a 2 l three-necked flask with a stirrer and reflux condenser and were heated to 150° C., during which splitting off of hydrogen chloride starts from about 110° C. After 5 hours, the mixture is heated to 180° C. and kept at this temperature for 3 hours. Thereafter, unreacted benzotrichloride and benzoic acid and the by-product benzoyl chloride are separated off by incipient distillation in vacuo (140°-180° C., 200-20 mbars) (960 g of distillate). With benzoic acid Patent; Bayer Aktiengesellschaft; US4562010; (1985); (A1) English View in Reaxys O

Rx-ID: 758118 View in Reaxys 2/294 Yield 100 %

Conditions & References With 1,2,3-Benzotriazole, thionyl chloride in dichloromethane, T= 20 °C , Substitution Chaudhari, Sachin S.; Akamanchi, Krishnacharya G.; Synlett; nb. 11; (1999); p. 1763 - 1765 View in Reaxys

100 %

With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 2h, T= 20 °C , Reflux Du, Xiu-Jiang; Bian, Qiang; Wang, Hong-Xue; Yu, Shu-Jing; Kou, Jun-Jie; Wang, Zhi-Peng; Li, Zheng-Ming; Zhao, Wei-Guang; Organic and Biomolecular Chemistry; vol. 12; nb. 29; (2014); p. 5427 - 5434 View in Reaxys

100 %

Syntheses of Aryl Acid Chlorides (4a-f) General procedure: The reaction scheme for the syntheses of aryl acid chlorides (4a-f) is shown in Scheme (1). Into a 250 mL two neck round bottomed flask equipped with a mechanical stirrer and a dropping funnel was placed in a thermostat bath. To a stirred solution of aryl acid (3a-f) 8 mM (3a: 0.98 g; 3b: 1.22g; 3c: 1.09 g; 3d: 1.34 g; 3e: 1.34 g; 3f: 1.18 g) in 100 mL CH2Cl2 at room temperature was added 16 mM (2.02 g) oxalyl chloride, 2 drops of DMF and the mixture was stirred at room temperature for 1h. The resulting mixture was concentrated under reduced pressure to afford acid chloride quantitatively and stored in air tight flask. With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 1h, T= 35 °C Patel, Chirag Bhupendra; Dhaduk, Bhavin Babu; Parsania, Parsotam Hari; Letters in Drug Design and Discovery; vol. 12; nb. 6; (2015); p. 505 - 511

3/118

2016-07-02 05:35:12

View in Reaxys 94 %

procedure for the preparation of aromatic carboxylic acid chlorides General procedure: The appropriate aromatic carboxylic acid (0.01 mol), thionyl chloride SOCl2 (1.6 mL, 0.02mol) and a dry toluene (40 mL) were heated at reflux until the disappearance of the carboxylic acid was fully completed (TLC; 2-8 h). After cooling, the mixture was concentrated on a rotary evaporator. The crude products were distilled under reduced pressure to yield the adequate pure acid chlorides (3a-h). With thionyl chloride in toluene, Reflux Kudelko, Agnieszka; Wroblowska, Monika; Tetrahedron Letters; vol. 55; nb. 21; (2014); p. 3252 - 3254 View in Reaxys

81 %

With thionyl chloride, Time= 1h, T= 100 °C Zhang, Chuan-Yu; Liu, Xing-Hai; Wang, Bao-Lei; Wang, Su-Hua; Li, Zheng-Ming; Chemical Biology and Drug Design; vol. 75; nb. 5; (2010); p. 489 - 493 View in Reaxys

75 %

With Amberlite IRA 93 (PCl5 form) in dichloromethane, Time= 6h, Heating Cainelli, Gianfranco; Contento, Michele; Manescalchi, Francesco; Plessi, Laura; Panunzio, Mauro; Synthesis; nb. 4; (1983); p. 306 - 308 View in Reaxys With hydrogenchloride, phosphorus pentoxide, T= 200 °C Friedel; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 68; (1869); p. 1559; Chemische Berichte; vol. 2; (1869); p. 80 View in Reaxys With potassium pyrosulfate, sodium chloride, T= 200 °C Beketow; Justus Liebigs Annalen der Chemie; vol. 109; (1859); p. 256 View in Reaxys With carbon disulfide, sulfur dichloride Carius; Justus Liebigs Annalen der Chemie; vol. 106; (1858); p. 302 View in Reaxys With thionyl chloride Heumann; Koechlin; Chemische Berichte; vol. 15; (1882); p. 1627 View in Reaxys Clark; Bell; ; vol. <3> 27 III; (1933); p. 97,100 View in Reaxys Likhomanenko, E. E.; Shpan'ko, I. V.; Litvinenko, L. M.; Goncharov, A. N.; Journal of Organic Chemistry USSR (English Translation); vol. 21; nb. 12; (1985); p. 2341 - 2347; Zhurnal Organicheskoi Khimii; vol. 21; nb. 12; (1985); p. 2559 - 2566 View in Reaxys Nakamura, Eiichi; Aoki, Satoshi; Sekiya, Kouichi; Oshino, Hiroji; Kuwajima, Isao; Journal of the American Chemical Society; vol. 109; nb. 26; (1987); p. 8056 - 8066 View in Reaxys Suzuki, Koji; Watanabe, Kazuhiko; Matsumoto, Yukihiro; Kobayashi, Mitsuru; Sato, Sayaka; Siswanta, Dwi; Hisamoto, Hideaki; Analytical Chemistry; vol. 67; nb. 2; (1995); p. 324 - 334 View in Reaxys With phosphorus trichloride, T= 60 - 120 °C Bechamp; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 42; (1856); p. 227; Journal fuer Praktische Chemie (Leipzig); vol. <1> 68; (1856); p. 492 View in Reaxys With phosphorus pentachloride

4/118

2016-07-02 05:35:12

Cahours; Annales de Chimie (Cachan, France); vol. <3> 23; (1848); p. 345; Justus Liebigs Annalen der Chemie; vol. 70; (1849); p. 44 View in Reaxys With phosphorus trichloride Scott; Hurley; Journal of the American Chemical Society; vol. 59; (1937); p. 1905,1906 View in Reaxys With zinc(II) chloride, phosphorus trichloride Clark; Bell; ; vol. <3> 27 III; (1933); p. 97,100 View in Reaxys With phosphorus pentachloride Clark; Bell; ; vol. <3> 27 III; (1933); p. 97,100 View in Reaxys With chlorine, trichlorophosphate, phosphorus trichloride Patent; Du Pont de Nemours and Co.; US2048768; (1934) View in Reaxys With potassium chloride, sodium chloride, trichlorophosphate Patent; I.G. Farbenind.; DE642519; (1935); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 23; p. 224 View in Reaxys With phosphorus trichloride Anschuetz; Justus Liebigs Annalen der Chemie; vol. 439; (1924); p. 274 View in Reaxys With thionyl chloride, T= 80 °C , Reaktion ueber mehrere Stufen Gattermann-Wieland; View in Reaxys With water, phosphorus trichloride, T= 100 °C , im Autoklaven Patent; Scheuble; DE251806; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 11; p. 70 View in Reaxys With sodium pyrosulfate, sodium chloride, T= 200 °C Beketow; Justus Liebigs Annalen der Chemie; vol. 109; (1859); p. 256 View in Reaxys With phosphorus pentachloride, Reaktion ueber mehrere Stufen Gattermann,L.; View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran Horne, Stephen; Rodrigo, Russell; Journal of Organic Chemistry; vol. 55; nb. 15; (1990); p. 4520 - 4522 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane Pellegata, R.; Italia, A.; Villa, M.; Palmisano, G.; Lesma, G.; Synthesis; nb. 5; (1985); p. 517 - 519 View in Reaxys With tetrachloromethane, cross-linked polymer (containing 2.50 mmol of phosphine/g), Time= 4h, Heating, Yield given Harrison, Charles R.; Hodge, Philip; Hunt, Barry J.; Khoshdel, Ezzatollah; Richardson, Graham; Journal of Organic Chemistry; vol. 48; nb. 21; (1983); p. 3721 - 3728

5/118

2016-07-02 05:35:12

View in Reaxys With thionyl chloride in benzene Hosangadi, B.D.; Chhaya, P.N.; Nimbalkar, M.M.; Patel, N.R.; Tetrahedron; vol. 43; nb. 22; (1987); p. 5375 - 5380 View in Reaxys With thionyl chloride, Time= 1h, Heating Itzhak, Yossef; Kalir, Asher; Weissman, Ben Avi; Cohen, Sasson; Journal of Medicinal Chemistry; vol. 24; nb. 5; (1981); p. 496 - 499 View in Reaxys With thionyl chloride, Time= 3h, Heating Andersson, Carl-Magnus; Hallberg, Anders; Journal of Organic Chemistry; vol. 53; nb. 2; (1988); p. 235 - 239 View in Reaxys With thionyl chloride in benzene, Heating Wan, A. S. C.; Ngiam, T. L.; Leung, S. L.; Go, M. L.; Heng, P. W. S.; et al.; Steroids; vol. 41; nb. 3; (1983); p. 309 320 View in Reaxys With thionyl chloride, Time= 15h Kolbe, Adelheid; Schuette, Horst-Robert; Zeitschrift fuer Chemie (Stuttgart, Germany); vol. 27; nb. 6; (1987); p. 215 - 216 View in Reaxys With thionyl chloride, Heating Chapyshev, S. V.; Kurkovskii, L. I.; Kartsev, V. G.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); vol. 36; nb. 4; (1987); p. 765 - 770; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; nb. 4; (1987); p. 837 - 842 View in Reaxys Brenstrum, Timothy J.; Brimble, Margaret A.; Stevenson, Ralph J.; Tetrahedron; vol. 50; nb. 16; (1994); p. 4897 - 4904 View in Reaxys With thionyl chloride Menegheli, Paulo; Farah, Joao P. S.; Seoud, Omar A. El; Berichte der Bunsen-Gesellschaft; vol. 95; nb. 12; (1991); p. 1610 - 1615 View in Reaxys Bowden, Keith; Chehel-Amiran, Mohsen; Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999); (1986); p. 2039 - 2044 View in Reaxys With thionyl chloride, Time= 1h, Heating Peters, J. A.; Bekkum, H. van; Recueil: Journal of the Royal Netherlands Chemical Society; vol. 100; nb. 1; (1981); p. 21 - 24 View in Reaxys With phosphorus pentachloride Koden; Takenaka; Kusabayashi; Molecular crystals and liquid crystals; vol. 88; nb. 1-4; (1982); p. 137 - 150 View in Reaxys With thionyl chloride in chloroform, Time= 6h, Heating Vansdadia; Vikani; Rarekh; Journal of the Indian Chemical Society; vol. 65; nb. 11; (1988); p. 782 - 783 View in Reaxys With oxalyl dichloride in dichloromethane, T= 0 - 20 °C

6/118

2016-07-02 05:35:12

Fisher; Caroon; Stabler; Lundberg; Zaidi; Sorensen; Sparacino; Muchowski; Canadian Journal of Chemistry; vol. 72; nb. 1; (1994); p. 142 - 145 View in Reaxys With thionyl chloride, Time= 2h, Heating Erol; Calis; Demirdamar; Yulug; Ertan; Journal of Pharmaceutical Sciences; vol. 84; nb. 4; (1995); p. 462 - 465 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in benzene, Time= 18h Aveline, Beatrice M.; Kochevar, Irene E.; Redmond, Robert W.; Journal of the American Chemical Society; vol. 117; nb. 38; (1995); p. 9699 - 9708 View in Reaxys With thionyl chloride in N,N,N,N,N,N-hexamethylphosphoric triamide, acetonitrile, Time= 0.5h, T= -5 - 0 °C Takada, Susumu; Sasatani, Takashi; Chomei, Nobuo; Adachi, Makoto; Fujishita, Toshio; Eigyo, Masami; Murata, Shunji; Kawasaki, Kazuo; Matsushita, Akira; Journal of Medicinal Chemistry; vol. 39; nb. 14; (1996); p. 2844 - 2851 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide, Time= 48h, Ambient temperature Musso; Boswell; Mehta; Soroko; Burchall; European Journal of Medicinal Chemistry; vol. 31; nb. 4; (1996); p. 331 - 334 View in Reaxys With 1,1,1,3,3,3-hexachloro-propan-2-one, triphenylphosphine in dichloromethane, Time= 0.333333h, T= -78 °C Villeneuve; Chan; Tetrahedron Letters; vol. 38; nb. 37; (1997); p. 6489 - 6492 View in Reaxys With tetrachloromethane, Cross-linked polystyrene containing 2.00 mmol of phosphine, Time= 0.5h, T= 77 °C , var. of time, and var. of conc. of CCl4 (Tab. VI), Product distribution, Mechanism Harrison, Charles R.; Hodge, Philip; Hunt, Barry J.; Khoshdel, Ezzatollah; Richardson, Graham; Journal of Organic Chemistry; vol. 48; nb. 21; (1983); p. 3721 - 3728 View in Reaxys With benzotrichloride, iron(III) chloride in benzene, T= 55 °C , ΔE(excit.), var. temp., var. conc. of benzotrichloride and FeCl3, Product distribution, Rate constant, Thermodynamic data Freidlin, E. G.; Journal of Organic Chemistry USSR (English Translation); vol. 17; nb. 6; (1981); p. 1129 - 1132; Zhurnal Organicheskoi Khimii; vol. 17; nb. 6; (1981); p. 1275 - 1279 View in Reaxys With thionyl chloride, T= 60 °C , Rate constant Vulakh, E. L.; Nemleva, S. A.; Ivanova, V. M.; Kaminskaya, E. G.; Gitis, S. S.; Journal of Organic Chemistry USSR (English Translation); vol. 19; (1983); p. 1663 - 1670; Zhurnal Organicheskoi Khimii; vol. 19; (1983); p. 1898 1906 View in Reaxys With thionyl chloride, T= 60 °C , also at 50 deg C; also in benzene at 60 deg C and CCl4, Rate constant, Kinetics Vulakh, E. L.; Nemleva, S. A.; Ivanova, V. M.; Kaminskaya, E. G.; Gitis, S. S.; Doklady Chemistry; vol. 270; (1983); p. 161 - 164; Dokl. Akad. Nauk SSSR Ser. Khim.; vol. 270; nb. 2; (1983); p. 333 - 336 View in Reaxys With N,N-dimethyl-formamide in benzene, T= 20 - 40 °C , ΔH(act.), ΔS(act.); chlorodehydration of benzoic acids with carbonyl chloride in the presence of DMF; rates; kinetics and mechanism, Rate constant, Thermodynamic data Vulakh; Militsin; Russian Journal of Organic Chemistry; vol. 32; nb. 11; (1996); p. 1704 - 1705 View in Reaxys With thionyl chloride in tetrahydrofuran, Chlorination

7/118

2016-07-02 05:35:12

Colthurst, Matthew J.; Williams, Andrew; Journal of the Chemical Society. Perkin Transactions 2; nb. 8; (1997); p. 1493 - 1497 View in Reaxys With thionyl chloride, Heating, Substitution Zhang, Youming; Wei, Taibao; Lu, Jinren; Synthetic Communications; vol. 28; nb. 17; (1998); p. 3243 - 3248 View in Reaxys With trichloroacetonitrile, triphenylphosphine in acetonitrile, Time= 0.666667h, T= 20 °C , Chlorination Jang, Doo Ok; Park, Doo Jin; Joonggon, Kim; Tetrahedron Letters; vol. 40; nb. 29; (1999); p. 5323 - 5326 View in Reaxys With thionyl chloride, Time= 3h, Heating Mannhold, Raimund; Cruciani, Gabriele; Weber, Horst; Lemoine, Horst; Derix, Andrea; Weichel, Claus; Clementi, Monica; Journal of Medicinal Chemistry; vol. 42; nb. 6; (1999); p. 981 - 991 View in Reaxys With thionyl chloride, Time= 2h, Heating, Substitution Pau, Amedeo; Boatto, Gianpiero; Palomba, Michele; Asproni, Battistina; Cerri, Riccardo; Palagiano, Francesco; Filippelli, Walter; Falcone, Giuseppe; Motola, Giulia; Farmaco; vol. 54; nb. 8; (1999); p. 524 - 532 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide, Time= 1h, T= 80 °C , Substitution Krishnan; Chowdary; Dubey; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 39; nb. 5; (2000); p. 329 - 333 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Chlorination Young, Jonathan R.; Huang, Song X.; Chen, Irene; Walsh, Thomas F.; DeVita, Robert J.; Wyvratt Jr., Matthew J.; Goulet, Mark T.; Ren, Ning; Lo, Jane; Yang, Yi Tien; Yudkovitz, Joel B.; Cheng, Kang; Smith, Roy G.; Bioorganic and Medicinal Chemistry Letters; vol. 10; nb. 15; (2000); p. 1723 - 1727 View in Reaxys With PS-Ph3P resin, trichloroacetonitrile in dichloromethane, T= 20 °C Buchstaller; Ebert; Anlauf; Synthetic Communications; vol. 31; nb. 7; (2001); p. 1001 - 1005 View in Reaxys With Wang resin-CH2-O-(...)-[4-(2,6-dichloro-1,3,5-triazine)], triethylamine in dichloromethane, T= 20 °C Luo, Guanglin; Xu, Li; Poindexter, Graham S.; Tetrahedron Letters; vol. 43; nb. 49; (2002); p. 8909 - 8912 View in Reaxys With thionyl chloride, Time= 0.5h, Heating Lee, Chang Kiu; Yu, Ji Sook; Ji, Young Ran; Journal of Heterocyclic Chemistry; vol. 39; nb. 6; (2002); p. 1219 1227 View in Reaxys With thionyl chloride, Time= 2h, T= 80 °C Karimi, Farhad; Langstroem, Bengt; Organic and Biomolecular Chemistry; vol. 1; nb. 3; (2003); p. 541 - 546 View in Reaxys With thionyl chloride, phosphazenium chloride on SBA-15 and silica gel PZ in dichloromethane, Time= 2.5h, T= 40 °C Kim, Keun-Sik; Kim, Jong-Ho; Seo, Gon; Chemical Communications; nb. 3; (2003); p. 372 - 373 View in Reaxys 2.G; 3.17 :To a suspension (or solution) of the corresponding carboxylic acid (1 eq.) in DCM (0.25 M), were added oxalyl chloride (2.5 eq.) and DMF (1 drop). The mixture was stirred at RT for 2 hours, and then evaporated, yielding

8/118

2016-07-02 05:35:12

the corresponding acyl chloride, which was used without further purification.The acyl chloride was dissolved in a minimum of acetonitrile, and then added to a solution of Intermediate 2 (1 eq.) in acetonitrile (0.25 M). The reaction mixture was stirred for 2 to 12 hours at RT (or at 4O0C) under a nitrogen atmosphere. The reaction mixture was evaporated. The residue was partitioned between water and DCM. The organic layer was washed with brine, and then was dried over MgSO4. The organic layer was evaporated. The residue was purified either by flash chromatography on silica gel or preparative HPLC. EPO <DP n="56"/>The ferf-butyloxycarbonyl group was removed using HCI gas (or 3N HCI) in a suitable solvent (methanol, diethyl ether, or 1 ,4-dioxane).; Compound 17: 4-(1-amino-ethyl)-3-benzoylamino-λ/-pyridin-4-yl-benzamide dihydrochloric acid salt2HClThe title compound was prepared according to the general Protocol G, starting from Intermediate 2 and benzoic acid, yielding a pale orange powder (45 percent overall yield). Tret: 0.92 min, ES+:361 ; ES': 359. Purity: 95 percent. 1H NMR (300 MHz, DMSO-d6): 1.52 ppm (d, 3H, J = 6.8 Hz); 4.55-4.63 ppm (m, 1 H); 7.52-7.65 ppm (m, 3H); 7.91 ppm (d, 1 H1 J = 8.3 Hz); 8.03-8.10 ppm (m, 3H); 8.14 ppm (d, 1 H, J = 8.3 Hz); 8.33 ppm (d, 2H, J = 6.9 Hz); 8.54-8.63 ppm (m, 2H); 8.74 ppm (d, 2H, J = 7.1 Hz); 10.57 ppm (s, 1 H); 11.68 ppm (s, 1 H). With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 2h, T= 20 °C Patent; DEVGEN N.V.; WO2007/42321; (2007); (A2) English View in Reaxys 34.1 :Step 1<469> As shown in the above-described reaction formula, 30-40 equivalent amount of anhydrous benzene was added to 1.5 equivalent amount of benzoic acid in round flask. Two drop of jV,/f-dimethyl formamide and 7.5 equivalent amount of thionyl chloride were added thereto and performed to refux for 5 hours at 70-80°C .<470> The reaction solution was cooled to room temperature and concentrated in vaccuo to obtain benzoyl chloride. With thionyl chloride, N,N-dimethyl-formamide in benzene, Time= 5h, T= 70 - 80 °C , Heating / reflux Patent; PARK, Yong Jin; WO2008/4817; (2008); (A1) English View in Reaxys 1 :2 ml of oxalyl chloride (0.0228 mol) were added dropwise to a solution, cooled to O0C, of benzoic acid (2.32 g, 0.019 mol) in 20 ml of anhydrous dichloromethane and of 0.5 ml of DMF. The mixture was left to stir for 15 minutes at O0C and then for 3 hours at lab. temperature. The reaction mixture was concentrated under vacuum. The yellow solid obtained was solubilized in 20 ml of dichloromethane and cooled to O0C. 3-Aminopropylmethylbis (trimethylsiloxy) silane (5.25 g, 0.019 mol) solubilized in 10 ml of anhydrous dichloromethane, and then diisopropylethylamine (9.5 ml, 0.057 mol) were added dropwise thereto. After the solvent had been evaporated off under vacuum, the orangey oil obtained was taken up in 100 ml of ethyl acetate. After two washes of the organic phase with water and then with a saturated solution of sodium chloride, it was dried over sodium sulphate. After filtration and evaporation of the solvent, the orangey oil obtained was chromatographed on silica (eluent: heptane/EtOAc 95:5), to give 5.1 g (yield: 70percent) of a pale yellow oil of the compound of Example 1. With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide, Time= 3.25h, T= 0 - 20 °C Patent; L'OREAL; WO2008/64979; (2008); (A2) English View in Reaxys With thionyl chloride, Time= 4h, Reflux Chenot, Elodie-Denise; Rodriguez-Dominguez, Juan Carlos; Hannewald, Paul; Comel, Alain; Kirsch, Gilbert; Journal of Heterocyclic Chemistry; vol. 45; nb. 5; (2008); p. 1429 - 1435 View in Reaxys With trichloroacetamide, triphenylphosphine in dichloromethane, Time= 1h, Reflux Chantarasriwong, Oraphin; Jang, Doo Ok; Chavasiri, Warinthorn; Synthetic Communications; vol. 38; nb. 16; (2008); p. 2845 - 2856 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide, Time= 0.5h, T= 20 °C , Inert atmosphere Marchais-Oberwinkler, Sandrine; Krachten, Patricia; Frotscher, Martin; Ziegler, Erika; Neugebauer, Alexander; Bhoga, Umadevi; Bey, Emmanuel; Mueller-Vieira, Ursula; Messinger, Josef; Thole, Hubert; Hartmann, Rolf W.; Journal of Medicinal Chemistry; vol. 51; nb. 15; (2008); p. 4685 - 4698 View in Reaxys With thionyl chloride, Time= 5h, T= 80 °C

9/118

2016-07-02 05:35:12

Li, Hongcai; Wang, Chao; Sanchez, Tino; Tan, Yanmei; Jiang, Chunying; Neamati, Nouri; Zhao, Guisen; Bioorganic and Medicinal Chemistry; vol. 17; nb. 7; (2009); p. 2913 - 2919 View in Reaxys With thionyl chloride, Time= 5h, Reflux Xu, Bixue; Huang, Zhengming; Liu, Changxiao; Cai, Zegui; Pan, Weidong; Cao, Peixue; Hao, Xiaojiang; Liang, Guangyi; Bioorganic and Medicinal Chemistry; vol. 17; nb. 8; (2009); p. 3118 - 3125 View in Reaxys 9.1 :Thiazolidine-2-thione (0.1 mol) was dissolved in anhydrous methylene chloride (50 mL), followed by addition of Triethylamine (0.13 mmol). Then a methylene chloride solution (20 mL) containing acyl chloride or anhydride (0.11 mol) was slowly added dropwise under ice bath, wherein the acyl chloride was prepared from the corresponding acid by refluxing in thionyl chloride or reacting with oxalyl chloride at room temperature in a solution of anhydrous methylene chloride treated by refluxing with calcium hydride. The reaction was carried out for a few hours at room temperature while monitored by TLC, and then quenched when the raw material was exhausted completely. After the reaction was completed, the reaction mixture was washed with water. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resultant product was recrystallized from ether-hexane to give the ligand III (N-acyl thiazolidine-2-thione). 1: 3-benzoyl-thiazolidine-2-thione 1NMR (CDCl3, 300 MHz): δ: 7.71 (d, J = 6.9, 2 H), 7.51 - 7.38 (m, 3 H), 4.51 (t, J = 7.25 Hz, 2 H), 3.44 (t, J = 7.25 Hz, 2 H). With thionyl chloride in dichloromethane, Reflux, Product distribution / selectivity Patent; Shanghai Institute of Materia Medica, Chinese Academy of Sciences; EP2119720; (2009); (A1) English View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 2.5h, T= 0 - 20 °C , Inert atmosphere Buettner, Anita; Seifert, Katrin; Cottin, Thomas; Sarli, Vasiliki; Tzagkaroulaki, Lito; Scholz, Stefan; Giannis, Athanassios; Bioorganic and Medicinal Chemistry; vol. 17; nb. 14; (2009); p. 4943 - 4954 View in Reaxys An amount of 500 g of benzoic acid was dissolved in 2000 ml of acetone, and 400 g of thionyl chloride was added dropwise over 3 hours. Thereafter, the mixture was stirred at a room temperature overnight under reflux. The solvent and unreacted thionyl chloride were removed to give 231 g of benzoyl chloride. Subsequently, the thus obtained benzoyl chloride was dissolved in 2000 ml of acetone and decompressed to 25 mmHg with an aspirator in a cooled state at 5° C. or less, and thereafter ammonia gas was purged therein. The reaction was stopped when the reaction system returned to normal pressure, and the reaction mixture was filtered under reduced pressure to obtain 169 g of ammonium benzoate. After the ammonium benzoate was washed with 1000 ml of water and then dissolved in 1N aqueous ice-cooled sodium hydroxide solution, bromine was added thereto. Thereby, the hydrolysis and decarboxylation was caused through the Hoffmann rearrangement to give the target 10.9 g of aniline. With thionyl chloride in acetone, T= 20 °C , Reflux Patent; FUJIKURA, Keitaro; US2009/306431; (2009); (A1) English View in Reaxys With thionyl chloride, Time= 2h, Reflux Yu, Zhiyi; Shi, Guanying; Sun, Qiu; Jin, Hong; Teng, Yun; Tao, Ke; Zhou, Guoping; Liu, Wei; Wen, Fang; Hou, Taiping; European Journal of Medicinal Chemistry; vol. 44; nb. 11; (2009); p. 4726 - 4733 View in Reaxys With thionyl chloride, triethylamine in tetrahydrofuran, T= 20 °C Lehmann, Fredrik; Currier, Erika A.; Clemons, Bryan; Hansen, Lars K.; Olsson, Roger; Hacksell, Uli; Luthman, Kristina; Bioorganic and Medicinal Chemistry; vol. 17; nb. 13; (2009); p. 4657 - 4665 View in Reaxys With thionyl chloride, Time= 2h, Reflux Sanmartin, Carmen; Plano, Daniel; Dominguez, Enrique; Font, Maria; Calvo, Alfonso; Prior, Celia; Encio, Ignacio; Palop, Juan Antonio; Molecules; vol. 14; nb. 9; (2009); p. 3313 - 3338 View in Reaxys With oxalyl dichloride in dichloromethane

10/118

2016-07-02 05:35:12

Altenkaemper, Mirko; Bechem, Benjamin; Perruchon, Johann; Heinrich, Swetlana; Maedel, Andrea; Ortmann, Regina; Dahse, Hans-Martin; Freunscht, Ellen; Wang, Yulin; Rath, Jennifer; Stich, August; Hitzler, Manuela; Chiba, Peter; Lanzer, Michael; Schlitzer, Martin; Bioorganic and Medicinal Chemistry; vol. 17; nb. 22; (2009); p. 7690 - 7697 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 - 20 °C Flipo, Marion; Charton, Julie; Hocine, Akila; Dassonneville, Sandrine; Deprez, Benoit; Deprez-Poulain, Rebecca; Journal of Medicinal Chemistry; vol. 52; nb. 21; (2009); p. 6790 - 6802 View in Reaxys 14 :Nitrobenzoic acid (6.1 g, 1.1 equivalent ratio, Aldrich) was dissolved in 15 ml dimethylacetamide (DMAC, Aldrich) at 00C and then thionyl chloride (6.21 g, 1.15 equivalent ratio) was gradually added to the solution. After the mixture solution was stirred for 10 min at 00C, the mixture of l-(3-amino-2-hydroxy-phenyl)-ethanone (6.86 g, 1 equivalent ratio) dissolved in 15 ml dimethylacetamide (DMAC, Aldrich) was slowly added to the mixture solution, and thermally stirred for 5 hrs at 25°C. The reaction mixture was mixed with 40 ml H2O and stirred for 1 hr at 250C. The solid material obtained by filtering the solid material produced was washed with 20 ml H2O and then dried at 600C with hotwind, obtaining 11.24 g (yield rate: 97percent): 1H NMR (300 MHz, DMSO) δ 10.13 (bs, IH) 9.64 (bs, IH) 7.75-7.85 (m, 4H) 2.47 (s, 3H). With thionyl chloride in ISOPROPYLAMIDE, T= 0 °C Patent; PHARMACOSTECH CO., LTD.; KIM, Jae Won; CHA, Young Gwan; RYU, Hyung Chul; KIM, Sun Joo; WO2010/2075; (2010); (A1) English View in Reaxys With thionyl chloride, Time= 6h, T= 20 °C , Reflux Tian, Mei; Zhang, Bao-Yan; Cong, Yue-Hua; Zhang, Na; Yao, Dan-Shu; Journal of Molecular Structure; vol. 923; nb. 1-3; (2009); p. 39 - 44 View in Reaxys 9 :Preparation Example 9Preparation of ligand III (N-acyl thiazolidine-2-thione) Thiazolidine-2-thione (0.1 mol) was dissolved in anhydrous methylene chloride (50 mL), followed by addition of Triethylamine (0.13 mmol). Then a methylene chloride solution (20 mL) containing acyl chloride or anhydride (0.11 mol) was slowly added dropwise under ice bath, wherein the acyl chloride was prepared from the corresponding acid by refluxing in thionyl chloride or reacting with oxalyl chloride at room temperature in a solution of anhydrous methylene chloride treated by refluxing with calcium hydride. The reaction was carried out for a few hours at room temperature while monitored by TLC, and then quenched when the raw material was exhausted completely. After the reaction was completed, the reaction mixture was washed with water. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The resultant product was recrystallized from ether-hexane to give the ligand III (N-acyl thiazolidine-2-thione).1: 3-benzoyl-thiazolidine-2-thione1H NMR (CDCl3, 300 MHz): δ: 7.71 (d, J=6.9, 2H), 7.51-7.38 (m, 3H), 4.51 (t, J=7.25 Hz, 2H), 3.44 (t, J=7.25 Hz, 2H). With thionyl chloride in dichloromethane, Reflux, Product distribution / selectivity Patent; Shanghai Institute of Materia Medica, Chinese Academy of Sciences; US2010/113498; (2010); (A1) English View in Reaxys With thionyl chloride, Time= 6h, T= 20 - 78 °C Tian, Mei; Zhang, Bao-Yan; Cong, Yue-Hua; He, Xiao-Zhi; Zhang, Bing; Journal of Molecular Structure; vol. 937; nb. 1-3; (2009); p. 131 - 135 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane Shi, Yan; Li, Chi; O'Connor, Stephen P.; Zhang, Jing; Shi, Mengxiao; Bisaha, Sharon N.; Wang, Ying; Sitkoff, Doree; Pudzianowski, Andrew T.; Huang, Christine; Klei, Herbert E.; Kish, Kevin; Yanchunas Jr., Joseph; Liu, Eddie C.-K.; Hartl, Karen S.; Seiler, Steve M.; Steinbacher, Thomas E.; Schumacher, William A.; Atwal, Karnail S.; Stein, Philip D.; Bioorganic and Medicinal Chemistry Letters; vol. 19; nb. 24; (2009); p. 6882 - 6889 View in Reaxys

11/118

2016-07-02 05:35:12

With thionyl chloride, N,N-dimethyl-formamide, Time= 5h, Reflux Zhao, Wanyi; Feng, Xiue; Ban, Shurong; Lin, Wenhan; Li, Qingshan; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 14; (2010); p. 4132 - 4134 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide in dichloromethane, Time= 5h, T= 45 °C Shi, Jianyou; Xu, Guobin; Zhu, Wei; Ye, Haoyu; Yang, Shengyong; Luo, Youfu; Han, Jing; Yang, Jincheng; Li, Rui; Wei, Yuquan; Chen, Lijuan; Bioorganic and Medicinal Chemistry Letters; vol. 20; nb. 14; (2010); p. 4273 4278 View in Reaxys With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide, Time= 3h, Inert atmosphere Stefely, Jonathan A.; Palchaudhuri, Rahul; Miller, Patricia A.; Peterson, Rebecca J.; Moraski, Garrett C.; Hergenrother, Paul J.; Miller, Marvin J.; Journal of Medicinal Chemistry; vol. 53; nb. 8; (2010); p. 3389 - 3395 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Inert atmosphere Jones, Ian M.; Hamilton, Andrew D.; Organic Letters; vol. 12; nb. 16; (2010); p. 3651 - 3653 View in Reaxys With thionyl chloride, Time= 3h, Reflux Xu, Ke-Ping; Zhang, Yuan-Yuan; Luo, Juan; Chen, Shan-Li; Wang, Yu-Liang; Journal of Chemical Research; nb. 6; (2010); p. 354 - 357 View in Reaxys With thionyl chloride, Reflux Dubey, Sonal; Jain, Vinod; Precthi; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 48; nb. 11; (2009); p. 1571 - 1576 View in Reaxys Arce, Mariana P.; Rodriguez-Franco, Maria Isabel; Gonzalez-Munoz, Gema C.; Perez, Concepcion; Lopez, Beatriz; Villarroya, Mercedes; Lopez, Manuela G.; Garcia, Antonio G.; Conde, Santiago; Journal of Medicinal Chemistry; vol. 52; nb. 22; (2009); p. 7249 - 7257 View in Reaxys Prajapati; Modi, Vishal P.; Journal of the Chilean Chemical Society; vol. 55; nb. 2; (2010); p. 240 - 243 View in Reaxys 23.1 :Benzoic acid (5.0 g) in thionyl chloride (10 mL) was refluxed for 1 hour and then cooled in air. The reaction solvent was removed under reduced pressure, and the residue was dissolved in methylene chloride (50 mL). Aminomalonic acid diethyl ester hydrochloride (7.53 g) was added to the solution, and the mixture was refluxed for 17 hours and then cooled in air. The solid that precipitated was collected through filtration, and the filtrate was partitioned between water and chloroform. The organic layer was sequentially washed with water, saturated aqueous sodium hydrogencarbonate, and saturated brine, and then dried over magnesium sulfate anhydrate. After a filtration step, the solvent was removed under reduced pressure, and the residue was purified through silica gel column chromatography (hexane - ethyl acetate), to thereby give a 2-benzoyl compound as an amorphous product (8.26 g, 72percent). 1H-NMR (400MHz, CDCl3) δ: 1.32(6H, t, J=7.1Hz), 4.25-4.38 (4H,m) , 5.35(1H, d, J=6.8Hz), 7.12(1H, d, J=6.1Hz), 7.43-7. 47(2H,m), 7.52-7.56(1H,m), 7.83-7.86(2H,m).LC-MSm/z:280(M+H)+. With thionyl chloride, Time= 1h, Heating / reflux Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1621537; (2006); (A1) English View in Reaxys With thionyl chloride Yu, Yan-Bo; Chen, Hong-Liang; Wang, Li-Yi; Chen, Xin-Zheng; Fu, Bin; Molecules; vol. 14; nb. 12; (2009); p. 4858 - 4865 View in Reaxys Cui, Zining; Ling, Yun; Li, Baoju; Li, Yongqiang; Rui, Changhui; Cui, Jingrong; Shi, Yanxia; Yang, Xinling; Molecules; vol. 15; nb. 6; (2010); p. 4267 - 4282

12/118

2016-07-02 05:35:12

View in Reaxys Yadav, Snehlata; Kumar, Pradeep; De Clercq, Erik; Balzarini, Jan; Pannecouque, Christophe; Dewan, Sharwan Kumar; Narasimhan, Balasubramanian; European Journal of Medicinal Chemistry; vol. 45; nb. 12; (2010); p. 5985 - 5997 View in Reaxys With thionyl chloride in N,N-dimethyl-formamide Khan, Khalid Mohammed; Mughal, Uzma Rasool; Khan, Ambreen; Naz, Farzana; Perveen, Shahnaz; Choudhary, M. Iqbal; Letters in Drug Design and Discovery; vol. 7; nb. 3; (2010); p. 188 - 193 View in Reaxys With thionyl chloride Duan, Li-Ping; Xue, Jia; Xu, Li-Li; Zhang, Hao-Bing; Molecules; vol. 15; nb. 10; (2010); p. 6941 - 6947 View in Reaxys With trichloroacetonitrile, triphenylphosphine in acetonitrile, T= 20 °C , Inert atmosphere Kim, Joong-Gon; Jang, Doo Ok; Synlett; nb. 20; (2010); p. 3049 - 3052; Art.No: U08710ST View in Reaxys With thionyl chloride Khan, Khalid Mohammed; Ahmed, Sumbul; Hussain, Sajjad; Ambreen, Nida; Perveen, Shahnaz; Choudhary, M. Iqbal; Letters in Drug Design and Discovery; vol. 7; nb. 4; (2010); p. 265 - 268 View in Reaxys With oxalyl dichloride in dichloromethane, Inert atmosphere, Reflux Ren, Hong; Wulff, William D.; Organic Letters; vol. 12; nb. 21; (2010); p. 4908 - 4911 View in Reaxys With thionyl chloride in dichloromethane, T= 0 - 50 °C Mathew, Ritta; Kruthiventi, Anil K.; Prasad, Jalli V.; Kumar, Sadula P.; Srinu, Garlapati; Chatterji, Dipankar; Chemical Biology and Drug Design; vol. 76; nb. 1; (2010); p. 34 - 42 View in Reaxys With thionyl chloride, triethylamine in chloroform Lee, Hyejin; Lee, Ji Ha; Kang, Sunwoo; Lee, Jin Yong; John, George; Jung, Jong Hwa; Chemical Communications; vol. 47; nb. 10; (2011); p. 2937 - 2939 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide in dichloromethane Yu, Xiaolong; Yang, Tao; Wang, Shulin; Xu, Hailiang; Gong, Hegui; Organic Letters; vol. 13; nb. 8; (2011); p. 2138 - 2141 View in Reaxys With oxalyl dichloride Yoo, Eun Jeong; Ma, Sandy; Mei, Tian-Sheng; Chan, Kelvin S. L.; Yu, Jin-Quan; Journal of the American Chemical Society; vol. 133; nb. 20; (2011); p. 7652 - 7655 View in Reaxys With thionyl chloride, Time= 2h, Reflux Yunus, Uzma; Kauser, Rukhsana; Bhatti, Moazzam H.; Zia-Ul-Haq, Muhammad; Wong, Wai-Yeung; Journal of Molecular Structure; vol. 995; nb. 1-3; (2011); p. 173 - 180 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 °C Amato, George; Roeloffs, Rosemarie; Rigdon, Greg C.; Antonio, Brett; Mersch, Theresa; McNaughton-Smith, Grant; Wickenden, Alan D.; Fritch, Paul; Suto, Mark J.; ACS Medicinal Chemistry Letters; vol. 2; nb. 6; (2011); p. 481 - 484

13/118

2016-07-02 05:35:12

View in Reaxys With oxalyl dichloride in toluene, Time= 3h, Reflux, Inert atmosphere Andreini, Manuel; Doknic, Daniela; Sutkeviciute, Ieva; Reina, Jose J.; Duan, Janxin; Chabrol, Eric; Thepaut, Michel; Moroni, Elisabetta; Doro, Fabio; Belvisi, Laura; Weiser, Joerg; Rojo, Javier; Fieschi, Franck; Bernardi, Anna; Organic and Biomolecular Chemistry; vol. 9; nb. 16; (2011); p. 5778 - 5786 View in Reaxys With thionyl chloride, Time= 0.5h, Reflux Mokale, Vinod J.; Raut, Mayuresh K.; Burange, Prashant J.; Dhoot, Navneet S.; Bhandari, Shashikant V.; Bothara, Kailash G.; Naik, Jitendra B.; Medicinal Chemistry; vol. 6; nb. 4; (2010); p. 211 - 218 View in Reaxys With thionyl chloride, Time= 2h, Reflux Wang, Liang; Dai, Fu-Ying; Zhu, Jie; Dong, Kui-Kui; Wang, Yu-Liang; Chen, Tian; Journal of Chemical Research; vol. 35; nb. 5; (2011); p. 313 - 316 View in Reaxys Dey; Basu; Journal of the Indian Chemical Society; vol. 88; nb. 10; (2011); p. 1581 - 1587 View in Reaxys With thionyl chloride in benzene, Time= 1h, Reflux Rajak, Harish; Behera, Chinmay K.; Pawar, Rajesh S.; Singour, Pradeep K.; Kharya, Murli Dhar; Chinese Chemical Letters; vol. 21; nb. 10; (2010); p. 1149 - 1152 View in Reaxys With thionyl chloride, Reflux Sabatini, Stefano; Gosetto, Francesca; Manfroni, Giuseppe; Tabarrini, Oriana; Kaatz, Glenn W.; Patel, Diixa; Cecchetti, Violetta; Journal of Medicinal Chemistry; vol. 54; nb. 16; (2011); p. 5722 - 5736 View in Reaxys With thionyl chloride, Time= 3h, Reflux Pareek, Alok K.; Joseph; Seth, Daya S.; Oriental Journal of Chemistry; vol. 26; nb. 4; (2010); p. 1533 - 1536 View in Reaxys T= 0 - 20 °C , Inert atmosphere Chan, Kelvin S. L.; Wasa, Masayuki; Wang, Xisheng; Yu, Jin-Quan; Angewandte Chemie - International Edition; vol. 50; nb. 39; (2011); p. 9081 - 9084 View in Reaxys 5.1.4. General procedure for the synthesis of compounds 9a-m General procedure: A mixture of substituted benzoic acid (0.008 mol) in thionyl chloride (5 mL) was stirred under refluxed for 2 h. After cooling to room temperature, the mixture was concentrated in vacuo to give crude product substituted benzoyl chloride as brown oils without further purification. To a mixture of 8a-c (0.002 mol), dry triethylamine (3 mL) and dry dichloromethane (10 mL), the solution of substituted benzoyl chloride in dry dichloromethane (10 mL) previous prepared was added. The whole mixture was stirred for overnight at room temperature. Water was added to the mixture and extracted with dichloromethane (25 .x. 2 mL). The combined organic layers were washed with brine and dried with Na2SO4, then concentrated in vacuo. Purification of the crude products by column chromatography eluting with petroleum-ethyl acetate (10:1) gave 9a-m. With thionyl chloride, Time= 2h, Reflux Lu, Xiaoyun; Wan, Baojie; Franzblau, Scott G.; You, Qidong; European Journal of Medicinal Chemistry; vol. 46; nb. 9; (2011); p. 3551 - 3563 View in Reaxys With thionyl chloride, T= 90 °C Sun, Juan; Yang, Yu-Shun; Li, Wei; Zhang, Yan-Bin; Wang, Xiao-Liang; Tang, Jian-Feng; Zhu, Hai-Liang; Bioorganic and Medicinal Chemistry Letters; vol. 21; nb. 20; (2011); p. 6116 - 6121

14/118

2016-07-02 05:35:12

View in Reaxys With oxalyl dichloride in dichloromethane Li, Xianghui; Fang, Yuyu; Deng, Pengchi; Hu, Jinchuan; Li, Tian; Feng, Wen; Yuan, Lihua; Organic Letters; vol. 13; nb. 17; (2011); p. 4628 - 4631 View in Reaxys Stage 1: in dichloromethane, Time= 0.166667h, Cooling with ice Stage 2: With thionyl chloride in dichloromethane, Time= 3.5h, T= 20 °C , Reflux Wang, Fang; He, Wen-Bin; Wang, Jin-He; Yan, Xiao-Sheng; Zhan, Ying; Ma, Ying-Ying; Ye, Li-Cai; Yang, Rui; Cai, Fu; Li, Zhao; Jiang, Yun-Bao; Chemical Communications; vol. 47; nb. 42; (2011); p. 11784 - 11786 View in Reaxys With thionyl chloride, Time= 2h, Reflux Du, Ya; Hyster, Todd K.; Rovis, Tomislav; Chemical Communications; vol. 47; nb. 44; (2011); p. 12074 - 12076 View in Reaxys With thionyl chloride in N,N-dimethyl-formamide, toluene, Time= 3h, T= 70 °C Kazaryants; Erastov; Galkin; Vyrypaev; Salikhov, Sh. M.; Abdrakhmanov; Chemistry of Heterocyclic Compounds; vol. 47; nb. 3; (2011); p. 355 - 362 View in Reaxys General procedure: Firstly, benzoyl chloride intermediates 1b, 2b, 3b, 4b, 5b and 6b were synthesized by reacting respective benzoic acids (1a-5a, Scheme 1) or picolinic acid (6a, Scheme 1) with thionyl chloride. In general, 1 g of benzoic acid compounds 1a, 2a, 3a, 4a, 5a or picolinic acid (6a) was added to thionyl chloride (12 mL) and then stirred with addition of 50 μL pyridine as a catalyst. The resulting mixture was refluxed until no gas overflowed. Then the excess thionyl chloride was removed off in vacuo, and the residue was directly used for the next step synthesis. With pyridine, thionyl chloride, T= 20 - 70 °C , Inert atmosphere Lue, Shuang; Luo, Qun; Hao, Xiang; Li, Xianchan; Ji, Liyun; Zheng, Wei; Wang, Fuyi; Bioorganic and Medicinal Chemistry Letters; vol. 21; nb. 23; (2011); p. 6964 - 6968 View in Reaxys With thionyl chloride in dichloromethane, Time= 2h, T= 20 - 50 °C Gonzalez Cabrera, Diego; Douelle, Frederic; Feng, Tzu-Shean; Nchinda, Aloysius T.; Younis, Yassir; White, Karen L.; Wu, Quoc; Ryan, Eileen; Burrows, Jeremy N.; Waterson, David; Witty, Michael J.; Wittlin, Sergio; Charman, Susan A.; Chibale, Kelly; Journal of Medicinal Chemistry; vol. 54; nb. 21; (2011); p. 7713 - 7719 View in Reaxys With thionyl chloride, T= 0 - 20 °C , Inert atmosphere Wasa, Masayuki; Chan, Kelvin S. L.; Yu, Jin-Quan; Chemistry Letters; vol. 40; nb. 9; (2011); p. 1004 - 1006 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 5h, T= 0 - 20 °C , Inert atmosphere Ano, Yusuke; Tobisu, Mamoru; Chatani, Naoto; Organic Letters; vol. 14; nb. 1; (2012); p. 354 - 357 View in Reaxys 6.1.7. General procedure for synthesis of substituted acid chlorides 10a-f and substituted acid azides 11a-d General procedure: A solution of the appropriate benzoic acid 9a-f (0.006 mol) in thionyl chloride (10 mL) was refluxed for 1 h, diluted with dry toluene and evaporated to afford the respective acid chlorides 10a-f. Crude 10a-d were dissolved in dry toluene (10 mL) and NaN3 (1.17 g, 0.018 mol) was added to the reaction mixture. The reaction mixture was refluxed for 1 h, filtered and evaporated under reduced pressure to afford 11a-d. The crude products 10e,f and 11a-d were used in the next step without any further purification. With thionyl chloride, Time= 1h, Reflux Aboul-Enein, Mohamed N.; El-Azzouny, Aida A.; Attia, Mohamed I.; Maklad, Yousreya A.; Amin, Kamilia M.; Abdel-Rehim, Mohamed; El-Behairy, Mohammed F.; European Journal of Medicinal Chemistry; vol. 47; nb. 1; (2012); p. 360 - 369

15/118

2016-07-02 05:35:12

View in Reaxys With thionyl chloride, Reflux Xue, Sijia; Ma, Xubo; Bu, Hongfei; Liu, Li; Xu, Xiao; Chinese Journal of Chemistry; vol. 29; nb. 10; (2011); p. 2153 - 2156 View in Reaxys Judge, Vikramjeet; Narasimhan, Balasubramanian; Ahuja, Munish; Sriram, Dharmarajan; Yogeeswari, Perumal; De Clercq, Erik; Pannecouque, Christophe; Balzarini, Jan; Medicinal Chemistry Research; vol. 21; nb. 7; (2012); p. 1451 - 1470 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 - 20 °C Pal, Sutanuka; Pal, Sudhir Chandra; Acta Chimica Slovenica; vol. 58; nb. 3; (2011); p. 596 - 599 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide, Time= 0.5h, T= 60 °C Attygalle, Athula B.; Nishshanka, Upul; Weisbecker, Carl S.; Journal of the American Society for Mass Spectrometry; vol. 22; nb. 9; (2011); p. 1515 - 1525 View in Reaxys With oxalyl dichloride in N,N-dimethyl-formamide, Time= 4h, T= 20 °C Pan, Li; Jiang, Ying; Liu, Zhen; Liu, Xing-Hai; Liu, Zhuo; Wang, Gang; Li, Zheng-Ming; Wang, Di; European Journal of Medicinal Chemistry; vol. 50; (2012); p. 18 - 26 View in Reaxys With thionyl chloride in dichloromethane, Inert atmosphere Tykwinski, Rik R.; Luu, Thanh; Synthesis (Germany); vol. 44; nb. 12; (2012); p. 1915 - 1922; Art.No: SS-2012Z0165-OP View in Reaxys With thionyl chloride, Time= 3.66667h, T= 20 - 80 °C Singh, Manjeet; Kumar, Sunil; Kumar, Ashwani; Kumar, Pradeep; Narasimhan, Balasubramanian; Medicinal Chemistry Research; vol. 21; nb. 4; (2012); p. 511 - 522 View in Reaxys 4.2. General procedure for the preparation of a solution of acid chlorides in CH2Cl2 General procedure: To a solution of carboxylic acids (1.7 mmol) in dry DMF (100 μL) and dry toluene (15 mL) under nitrogen atmosphere, freshly distillated thionyl chloride (3.4 mmol) was added and the solution was stirred at room temperature overnight. The solvent and thionyl chloride were removed under vacuum. The acid chloride was dissolved with dichloromethane (15 mL) under nitrogen atmosphere and directly used for the synthesis of the boronic acid. With thionyl chloride in N,N-dimethyl-formamide, toluene, T= 20 °C , Inert atmosphere Zervosen, Astrid; Bouillez, Andre; Herman, Alexandre; Amoroso, Ana; Joris, Bernard; Sauvage, Eric; Charlier, Paulette; Luxen, Andre; Bioorganic and Medicinal Chemistry; vol. 20; nb. 12; (2012); p. 3915 - 3924 View in Reaxys With thionyl chloride, T= 20 °C Zhang, Xing-Guo; Dai, Hui-Xiong; Wasa, Masayuki; Yu, Jin-Quan; Journal of the American Chemical Society; vol. 134; nb. 29; (2012); p. 11948 - 11951 View in Reaxys With bis(trichloromethyl) carbonate, Time= 3h, T= 40 °C Lin, Qi; Zhang, You-Ming; Li, Man-Lin; Wei, Tai-Bao; Synthetic Communications; vol. 42; nb. 22; (2012); p. 3251 3260 View in Reaxys With thionyl chloride, Time= 2h, Reflux

16/118

2016-07-02 05:35:12

Dey; Banerjee; Basu; Journal of the Indian Chemical Society; vol. 89; nb. 5; (2012); p. 653 - 660 View in Reaxys Guan, Li; Hao, Yanfeng; Chen, Lei; Wei, Meng-Lin; Jiang, Qin; Liu, Wen-Yuan; Zhang, Yan-Bo; Zhang, Jie; Feng, Feng; Qu, Wei; RSC Advances; vol. 6; nb. 27; (2016); p. 22827 - 22838 View in Reaxys With thionyl chloride in toluene, Reflux Yin, Hong; Shangguan, Yingying; Sui, Fengying; Yang, Xinji; Song, Guojie; Letters in Drug Design and Discovery; vol. 9; nb. 8; (2012); p. 780 - 788,9 View in Reaxys With thionyl chloride Ge, Hai-Xia; Zhang, Jian; Chen, Ling; Kou, Jun-Ping; Yu, Bo-Yang; Bioorganic and Medicinal Chemistry; vol. 21; nb. 1; (2013); p. 62 - 69 View in Reaxys Stage 1: With triethylamine in tetrahydrofuran, Time= 0.0833333h, T= -10 °C , Inert atmosphere Stage 2: With chloroformic acid ethyl ester in tetrahydrofuran, Time= 2h, T= -10 °C , Inert atmosphere Boulahjar, Rajaa; Ouach, Aziz; Matteo, Chiurato; Bourg, Stephane; Ravache, Myriam; Guevel, Remy Le; Marionneau, Severine; Oullier, Thibauld; Lozach, Olivier; Meijer, Laurent; Guguen-Guillouzo, Christiane; Lazar, Said; Akssira, Mohamed; Troin, Yves; Guillaumet, Gerald; Routier, Sylvain; Journal of Medicinal Chemistry; vol. 55; nb. 22; (2012); p. 9589 - 9606 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 20 °C Fevig, John M.; Feng, Jianxin; Rossi, Karen A.; Miller, Keith J.; Wu, Ginger; Hung, Chen-Pin; Ung, Thao; Malmstrom, Sarah E.; Zhang, Ge; Keim, William J.; Cullen, Mary Jane; Rohrbach, Kenneth W.; Qu, Qinling; Gan, Jinping; Pelleymounter, Mary Ann; Robl, Jeffrey A.; Bioorganic and Medicinal Chemistry Letters; vol. 23; nb. 1; (2013); p. 330 - 335 View in Reaxys With thionyl chloride in tetrahydrofuran Zhao, Huiping; Moroni, Elisabetta; Yan, Bin; Colombo, Giorgio; Blagg, Brian S. J.; ACS Medicinal Chemistry Letters; vol. 4; nb. 1; (2013); p. 57 - 62 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran, Time= 1h, T= 20 °C , Inert atmosphere, Solvent Fischer, Stefan; Wentsch, Heike K.; Mayer-Wrangowski, Svenja C.; Zimmermann, Markus; Bauer, Silke M.; Storch, Kirsten; Niess, Raimund; Koeberle, Solveigh C.; Gruetter, Christian; Boeckler, Frank M.; Rauh, Daniel; Laufer, Stefan A.; Journal of Medicinal Chemistry; vol. 56; nb. 1; (2013); p. 241 - 253 View in Reaxys With thionyl chloride, Time= 2h, Reflux Zheng, Shilong; Zhong, Qiu; Jiang, Quan; Mottamal, Madhusoodanan; Zhang, Qiang; Zhu, Naijue; Burow, Matthew E.; Worthylake, Rebecca A.; Wang, Guangdi; ACS Medicinal Chemistry Letters; vol. 4; nb. 2; (2013); p. 191 - 196 View in Reaxys With thionyl chloride in toluene, Time= 6h, Inert atmosphere, Reflux Schienebeck, Casi M.; Robichaux, Patrick J.; Li, Xiaoxun; Chen, Lianqing; Tang, Weiping; Chemical Communications; vol. 49; nb. 26; (2013); p. 2616 - 2618 View in Reaxys With thionyl chloride, Time= 3h, Reflux Judge, Vikramjeet; Narasimhan, Balasubramanian; Ahuja, Munish; Sriram, Dharmarajan; Yogeeswari, Perumal; De Clercq, Erik; Pannecouque, Christophe; Balzarini, Jan; Medicinal Chemistry; vol. 9; nb. 1; (2013); p. 53 - 76 View in Reaxys

17/118

2016-07-02 05:35:12

Zhang, Yang; Yang, Yan; Zhao, Sen; Yang, Zhichao; Yang, Hong; Fawcett, J. Paul; Li, Youxin; Gu, Jingkai; Sun, Tiemin; Molecules; vol. 18; nb. 12; (2013); p. 14920 - 14934 View in Reaxys Zhang, Tong-Xin; Zhang, Wei-Xi; Zhu, Hua-Jun; Liang, Long; Cheng, Zhi-Peng; Luo, Mei-Ming; Asian Journal of Chemistry; vol. 26; nb. 8; (2014); p. 2344 - 2350 View in Reaxys Synthesis and structural characterization of oxadiazole derivatives General procedure: Furthermore, the acyl chloride was prepared by the reaction of compound 3 with SOCl2. Briefly, the compound 3 (2.58 g, 10 mmol) was suspended in 50 mL of dichloromethane. After a drop of (CH3)2NCHO was added, SOCl2 (1.16 mL, 16 mmol) was dropwisely added. The mixture was stirred at room temperature for 1 h then heated at 40 °C until the formed gas was removed completely. The solvent and excess of reagents were removed in vacuum, and the acyl chloride was used without further purification. With thionyl chloride in dichloromethane, N,N-dimethyl-formamide, Time= 1h, T= 20 °C Zhao, Chao; Liu, Zai-Qun; Biochimie; vol. 95; nb. 4; (2013); p. 842 - 849 View in Reaxys With thionyl chloride in dichloromethane, N,N-dimethyl-formamide, Time= 3h, T= 60 °C , Inert atmosphere, Schlenk technique Tang, Qiuzheng; Xia, Dexin; Jin, Xiqing; Zhang, Qing; Sun, Xiao-Qiang; Wang, Congyang; Journal of the American Chemical Society; vol. 135; nb. 12; (2013); p. 4628 - 4631 View in Reaxys With thionyl chloride, Time= 4h, Reflux Bonsignore, Martina; Benaglia, Maurizio; Raimondi, Laura; Orlandi, Manuel; Celentano, Giuseppe; Beilstein Journal of Organic Chemistry; vol. 9; (2013); p. 633 - 640 View in Reaxys With thionyl chloride, T= 60 - 80 °C , Concentration Gao, Xi-Ai; Wang, Xian-Xue; Yan, Hao; Li, Jian; Yan, Ru-Long; Huang, Guo-Sheng; Journal of the Indian Chemical Society; vol. 90; nb. 3; (2013); p. 381 - 385 View in Reaxys 5.1.2 Synthesis of benzoyl chlorides General procedure: The corresponding benzoic acids were converted into benzoyl chlorides using thionylchloride as a halogenating agent, and the reaction was performed with each of the corresponding benzoic acids (6–10mmol) and 5mL of thionyl chloride using dry THF as a solvent, under a nitrogen atmosphere. The mixture was maintained at room temperature for 24h, and then the solvent, excess reagents and remaining HCl and SO2 were evaporated under vacuum. The unpurified benzoyl chloride was used immediately for the next reaction. With thionyl chloride in tetrahydrofuran, Time= 24h, T= 20 °C , Inert atmosphere Faundez-Parraguez, Manuel; Farias-Rabelo, Nicolas; Gonzalez-Gutierrez, Juan Pablo; Etcheverry-Berrios, Alvaro; Alzate-Morales, Jans; Adasme-Carreno, Francisco; Varas, Rodrigo; Bermudez, Isabel; Iturriaga-Vasquez, Patricio; Bioorganic and Medicinal Chemistry; vol. 21; nb. 10; (2013); p. 2687 - 2694 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 1.5h, T= 20 °C , Inert atmosphere Peixoto, Philippe Alexandre; Boulange, Agathe; Leleu, Stephane; Franck, Xavier; European Journal of Organic Chemistry; nb. 16; (2013); p. 3316 - 3327 View in Reaxys With thionyl chloride, Time= 5h, Reflux Guo, Dongcai; He, Wei; Liu, Bang; Gou, Lining; Li, Ruixia; Luminescence; vol. 28; nb. 3; (2013); p. 280 - 286 View in Reaxys 2.2 Synthesis of L1 General procedure: To a 250ml round-bottomed flask was added 2-cyanopyridine (2.08g, 20mmol), sodium azide (1.43g, 22mmol), zinc bromide (4.50g, 20mmol), and water (40mL). The reaction mixture was refluxed for 6h, cooled

18/118

2016-07-02 05:35:12

to room temperature. Then the mixture was basified by addition of 2.5 equiv of NaOH, filtered, acidified to pH 1, and filtered, and the solid was washed with water then 5-(2-Pyridyl)tetrazole (2.31g, 79percent) was obtained. Benzoyl chloride was synthesized by the following procedure (ii): benzoic acid (2.44g, 20mmol) was added into sulfurous oxychloride (20ml) and stirred at room temperature for 24h, excess sulfurous oxychloride was removed by vacuum evaporation. The obtained product was dried in vacuum, then 5-(2-pyridyl)tetrazole (2.96g, 20mmol) and pyridine (50ml) were added and refluxed for 72h (iii). The crude product was then purified by column chromatography. Yield 3.22g (59.6percent). 1HNMR (CDCl3): δ 7.474 (1H, m), 7.545 (3H, m), 7.898 (1H, m), 8.222 (1H, t), 8.242 (1H, t), 8.324 (1H, d, J=6.0), 8.828 (1H, d, J=3.6). Anal. Calc. For C13H9N3O: C, 69.95; H, 4.06; N, 18.82. Found: C, 69.93; H, 4.08; N, 18.84percent. IR (KBr pellet): 3055, 1616, 1547, 1481, 1452, 1387, 1146, 1072, 1024, 793, 715cm−1. With thionyl chloride, Time= 24h, T= 20 °C Shi, Lin-Fang; Li, Bin; Zhang, Li-Ming; Zuo, Qing-Hui; Yue, Shumei; Inorganica Chimica Acta; vol. 400; (2013); p. 91 - 98 View in Reaxys With ((1,3,5-triazine-2,4,6-triyl)tris(oxy))tris(triphenylphosphonium) chloride, Time= 0.5h, T= 140 - 150 °C Sugimoto, Osamu; Harada, Yukihiro; Tanji, Ken-Ichi; Heterocycles; vol. 86; nb. 2; (2012); p. 1583 - 1590 View in Reaxys With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide, Time= 3h Zheng, Baisong; Yao, Yuan; Liu, Zhen; Deng, Lisheng; Anglin, Justin L.; Jiang, Hong; Prasad, B.V. Venkataram; Song, Yongcheng; ACS Medicinal Chemistry Letters; vol. 4; nb. 6; (2013); p. 542 - 546 View in Reaxys With thionyl chloride in N,N-dimethyl-formamide, Time= 2h, Reflux Zhang, Fenglong; Du, Jin; Wang, Qing; Hu, Qinghua; Zhang, Jiong; Ding, Dazhong; Zhao, Yaxue; Yang, Fei; Wang, Enduo; Zhou, Huchen; Organic and Biomolecular Chemistry; vol. 11; nb. 32; (2013); p. 5310 - 5324 View in Reaxys With thionyl chloride in dichloromethane, Time= 2h, T= 20 °C Prashanth; Revanasiddappa; Medicinal Chemistry Research; vol. 22; nb. 6; (2013); p. 2665 - 2676 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 4h, T= 0 - 20 °C , Inert atmosphere Yu, Qingzhen; Zhang, Nana; Huang, Jianhui; Lu, Shaonan; Zhu, Yi; Yu, Xiaoxiao; Zhao, Kang; Chemistry - A European Journal; vol. 19; nb. 34; (2013); p. 11184 - 11188 View in Reaxys With thionyl chloride, Time= 4h, Inert atmosphere, Reflux Lu, Wenbin; Liang, Zhuye; Zhang, Yuwei; Wu, Fan; Qian, Qun; Gong, Hegui; Synthesis (Germany); vol. 45; nb. 16; (2013); p. 2234 - 2240; Art.No: SS-2013-Z0322-PSP View in Reaxys With thionyl chloride, Time= 5h, Reflux Raoof, Ali; Depledge, Paul; Hamilton, Niall M.; Hamilton, Nicola S.; Hitchin, James R.; Hopkins, Gemma V.; Jordan, Allan M.; Maguire, Laura A.; McGonagle, Alison E.; Mould, Daniel P.; Rushbrooke, Mathew; Small, Helen F.; Smith, Kate M.; Thomson, Graeme J.; Turlais, Fabrice; Waddell, Ian D.; Waszkowycz, Bohdan; Watson, Amanda J.; Ogilvie, Donald J.; Journal of Medicinal Chemistry; vol. 56; nb. 16; (2013); p. 6352 - 6370 View in Reaxys With phosphorus pentachloride Joshi, Akshada J.; Gadhwal, Manoj K.; Joshi, Urmila J.; D'Mello, Priscilla; Sinha, Ragini; Govil, Girjesh; Medicinal Chemistry Research; vol. 22; nb. 9; (2013); p. 4293 - 4299 View in Reaxys With thionyl chloride, Time= 1h, Reflux

19/118

2016-07-02 05:35:12

Soyer, Zeynep; Akgul, Ozlem; Tarikogullari, Ayse H.; Calis, Unsal; Medicinal Chemistry Research; vol. 22; nb. 10; (2013); p. 4708 - 4714 View in Reaxys With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide, Time= 2.5h, T= 0 - 20 °C Samanta, Sanjay; Lim, Ting Liang; Lam, Yulin; ChemMedChem; vol. 8; nb. 6; (2013); p. 994 - 1001 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide, Time= 3h, T= 60 °C Zhang, Ningning; Yang, Rui; Zhang-Negrerie, Daisy; Du, Yunfei; Zhao, Kang; Journal of Organic Chemistry; vol. 78; nb. 17; (2013); p. 8705 - 8711 View in Reaxys 43.2 : (2) (2) Synthesis of 4-(2,3-dihydrophytyloxy)benzoyl chloride The benzoic acid compound prepared in the above-mentioned Example 43-(1) was converted to the corresponding acid chloride in the same manner as in Example 4-(1) to give an oily compound. The present compound was directly used for the next step. Patent; Hirai, Kunihiro; Katayama, Satoshi; Torii, Takayoshi; Nakaya, Ryotaro; Takahashi, Daisuke; US2013/267697; (2013); (A1) English View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 - 20 °C , Inert atmosphere Zhang, Nana; Yu, Qingzhen; Chen, Ruixue; Huang, Jianhui; Xia, Yeqing; Zhao, Kang; Chemical Communications; vol. 49; nb. 82; (2013); p. 9464 - 9466 View in Reaxys With thionyl chloride, T= 55 °C Fernandez-Salas, Jose A.; Manzini, Simone; Nolan, Steven P.; Chemical Communications; vol. 49; nb. 84; (2013); p. 9758 - 9760 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 0.75h, T= 0 - 20 °C Yamada, Ayumi; Fujii, Shinya; Mori, Shuichi; Kagechika, Hiroyuki; ACS Medicinal Chemistry Letters; vol. 4; nb. 10; (2013); p. 937 - 941 View in Reaxys With thionyl chloride in N,N-dimethyl-formamide Rauf, Muhammad Khawar; Talib, Ammara; Badshah, Amin; Zaib, Sumera; Shoaib, Khurram; Shahid, Mohammad; Floerke, Ulrich; Imtiaz-Ud-Din; Iqbal, Jamshed; European Journal of Medicinal Chemistry; vol. 70; (2013); p. 487 - 496 View in Reaxys 4.2 Synthesis of acyl chlorides General procedure: To 5mL of previously distilled thionyl chloride were added 3mmol of the carboxylic acid, and immediately 3 drops of dimethylformamide (DMF). The reaction mixture was heated at 70°C for approximately 90min, forming a yellowish translucent solution. Excess of thionyl chloride was eliminated from the mixture with a rotary evaporator connected to a potassium hydroxide trap. Products obtained were pale yellow oils or solids. Acyl chlorides were employed directly for following reactions without further purification. With thionyl chloride in N,N-dimethyl-formamide, Time= 1.5h, T= 70 °C Garcia-Barrantes, Pedro M.; Lamoureux, Guy V.; Perez, Alice L.; Garcia-Sanchez, Rory N.; Martinez, Antonio R.; San Feliciano, Arturo; European Journal of Medicinal Chemistry; vol. 70; (2013); p. 548 - 557 View in Reaxys 7 : 4.2.7 Dimethyl-5-benzamidoisophthalate (5)

20/118

2016-07-02 05:35:12

The 5 mL SOCl2 was slowly added to 20 mL benzene solution, which containing benzoic acid (2 mmol, 244 mg), after adding 3 drops DMF, the mixture was refluxed over 24 h. The excess SOCl2 was removed by vacuum distillation. The reaction was soluble in 10 mL CH2Cl2, then was slowly added to a solution of 5-amino-isophthalic acid dimethyl ester (2 mmol, 420 mg) and NEt3 (1.60 mmol, 220 μL) in CH2Cl2 (20 mL) at 0 °C. The reaction mixture was allowed to warm slowly to room temperature and stirred for 12 h. The mixture was concentrated under vacuum. The crude product was direct used by next step. With thionyl chloride, N,N-dimethyl-formamide in benzene, Time= 24h, Reflux Zhu, Wenting; Wu, Xiao; He, Cheng; Duan, Chunying; Tetrahedron; vol. 69; nb. 48; (2013); p. 10477 - 10481 View in Reaxys 3.2. Synthesis of ethyl 4-(3-benzoylthioureido) benzoates (1a–j) General procedure: Variously substituted benzoic acids (0.02 mol) were treatedwith 2 mL (1.3 eq) of thionylchloride through a dropping funneland the reaction mixture was heated under reflux for 2–3 h yieldscorresponding acid chlorides. To a stirred solution of potassiumthiocyanate (1.2 g, 0.02 mol) in 10 mL dry acetone, placed in roundbottom flask fitted with a reflux condenser. (1.5 mL, 0.02 mol) offreshly prepared acid chlorides was added drop wise. After the initialreaction had subsided a solution of ethyl 4-animobenzoate(0.02 mol) in acetone (20 mL) was added slowly with constantstirring followed by reflux for 1–2 h. The mixture was poured intocrushed ice when the ethyl 4-(3-benzoylthioureido) benzoates(1a–j) precipitated as solid. The solid product was filtered, thendried and recrystallized from suitable solvent. With thionyl chloride, Reflux Saeed, Aamer; Khan, Muhammad Siraj; Rafique, Hummera; Shahid, Mohammad; Iqbal, Jamshed; Bioorganic Chemistry; vol. 52; (2014); p. 1 - 7 View in Reaxys General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5°C. With thionyl chloride, Time= 5h, Reflux Li, Liangjing; Ding, Hao; Wang, Baogang; Yu, Shichong; Zou, Yan; Chai, Xiaoyun; Wu, Qiuye; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 1; (2014); p. 192 - 194 View in Reaxys 2.3.1. General procedure for syntheses of benzoylferrocene derivatives General procedure: A mixture of 10.0 mmol benzoic acid derivatives 1, 50.0 mL chloroform, 1 to 2 drops of DMF as catalyst, and oxalyl chloride (1.90 g, 15.0 mmol) was stirred at room temperature for 3.0–4.0 h. The solvent and excess oxalyl chloride were removed by rotary evaporation to produce crude benzoyl chloride derivatives 2. With oxalyl dichloride, N,N-dimethyl-formamide in chloroform, T= 20 °C Jia, Jianhong; Cui, Yanhong; Han, Liang; Sheng, Weijian; Li, Yujin; Gao, Jianrong; Dyes and Pigments; vol. 104; (2014); p. 137 - 145 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 2h, T= 0 - 20 °C Feng, Chao; Loh, Teck-Peng; Angewandte Chemie - International Edition; vol. 53; nb. 10; (2014); p. 2722 - 2726; Angew. Chem.; vol. 126; nb. 10; (2014); p. 2760 - 2764,5 View in Reaxys 1 : General procedure for the synthesis of 10a-10p General procedure: The carboxylic acid (6.5mmol) was dissolved in excess thionyl chloride (10ml) and two drops of DMF. The mixture was kept 60°C for 2h and excess thionyl chloride was evaporated. The freshly prepared acyl chloride was then dissolved in 15ml of THF and the resulting solution was added to the mixture of 9a, 9b or 9c (5.5mmol) and sodium bicarbonate (13.5mmol).The resulting mixture was stirred for 8h at room temperature. After

21/118

2016-07-02 05:35:12

removing the solvent, the mixture was acidified with 1M HCl and the final product was purified by recrystallization in water/ethanol. With thionyl chloride, N,N-dimethyl-formamide, Time= 2h, T= 60 °C Han, Leiqiang; Wang, Lei; Hou, Xuben; Fu, Huansheng; Song, Weiguo; Tang, Weiping; Fang, Hao; Bioorganic and Medicinal Chemistry; vol. 22; nb. 5; (2014); p. 1529 - 1538 View in Reaxys 4.8. General procedure for the preparation of 8, 21a-d and 21g General procedure: To a solution of the corresponding carboxylic acid (3.6 mmol) inanhydrous CH2Cl2 (20 mL) was added thionyl chloride (2.6 mL,36 mmol). The reaction mixture was stirred at 40 C for 2 h, andthen concentrated in vacuo to dryness. The residuewas dissolved inanhydrous CH2Cl2 (20 mL), then p-methoxybenzyl alcohol (497 mg, 3.6 mmol) and excess triethylamine were added. The reactionmixture was stirred at room temperature until the TLC indicatedthe consumption of the starting material. An aqueous solution of10percent HCl was added to the reaction mixture. The aqueous layer wasextracted with CH2Cl2 (310 mL). The combined organic layerswere washed with brine, dried over anhydrous sodium sulfate,filtered, and concentrated in vacuo. The residue was purified byflash chromatography (petroleum ether/ethyl acetate 200:1 to20:1) to give the product. With thionyl chloride in dichloromethane, Time= 2h, T= 40 °C Chen, Dongyin; Xu, Chang; Deng, Jie; Jiang, Chunhuan; Wen, Xiaoan; Kong, Lingyi; Zhang, Ji; Sun, Hongbin; Tetrahedron; vol. 70; nb. 11; (2014); p. 1975 - 1983 View in Reaxys With thionyl chloride, Time= 3.5h, T= 76 - 80 °C , Reflux Li, Qian; Cui, Lin-Song; Zhong, Cheng; Jiang, Zuo-Quan; Liao, Liang-Sheng; Organic Letters; vol. 16; nb. 6; (2014); p. 1622 - 1625 View in Reaxys With oxalyl dichloride, tropone, triethylamine in dichloromethane, Time= 0.5h, T= 20 °C , Inert atmosphere Nguyen, Thanh V.; Bekensir, Alp; Organic Letters; vol. 16; nb. 6; (2014); p. 1720 - 1723 View in Reaxys With thionyl chloride, Time= 2h, Reflux Mohammad, Haroon; Mayhoub, Abdelrahman S.; Ghafoor, Adil; Soofi, Muhammad; Alajlouni, Ruba A.; Cushman, Mark; Seleem, Mohamed N.; Journal of Medicinal Chemistry; vol. 57; nb. 4; (2014); p. 1609 - 1615 View in Reaxys With thionyl chloride in dichloromethane, T= 0 - 5 °C Modh, Rahul P; Shah, Dhruvin; Chikhalia, Kishor H; Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry; vol. 52; nb. 10; (2013); p. 1318 - 1324 View in Reaxys 1. General Procedure for the Synthesis of Intermediates 1a-1e General procedure: SOCl2 (0.30 mol) was added to a solution of aromatic acid (0.06 mol) in CH2Cl2 (80 mL), the mixture was stirred and refluxed for 4 h, then evaporated until dryness to give compounds 1a-1e with colorless oily liquid which was immediately applied for further reaction as a crude product after quick weighing. With thionyl chloride in dichloromethane, Time= 4h, Reflux Guo, Xiaoke; Ma, Xianglei; Yang, Qian; Xu, Jing; Huang, Lu; Jia, Jianmin; Shan, Jiaojiao; Liu, Li; Chen, Weilin; Chu, Hongxi; Wei, Jinlian; Zhang, Xiaojin; Sun, Haopeng; Tang, Yiqun; You, Qidong; European Journal of Medicinal Chemistry; vol. 81; (2014); p. 89 - 94 View in Reaxys With phosphorus trichloride Niu, Teng; Wang, Ke-Hu; Huang, Danfeng; Xu, Changming; Su, Yingpeng; Hu, Yulai; Fu, Ying; Synthesis (Germany); vol. 46; nb. 3; (2014); p. 320 - 330; Art.No: SS-2013-H0629-OP View in Reaxys

22/118

2016-07-02 05:35:12

With thionyl chloride, Reflux Saeed, Aamer; Rafique, Hummera; Turkish Journal of Chemistry; vol. 37; nb. 6; (2013); p. 909 - 916 View in Reaxys Wang, Shudong; Zhang, Lei; Jin, Yongsheng; Tang, Jin Hao; Su, Hua; Yu, Shichong; Ren, Haixiang; Asian Journal of Chemistry; vol. 26; nb. 8; (2014); p. 2362 - 2364 View in Reaxys With thionyl chloride Li, Chun; Yang, Wen; Liu, Huanhuan; Li, Mengying; Zhou, Weiqun; Xie, Juan; Molecules; vol. 18; nb. 12; (2013); p. 15737 - 15749 View in Reaxys Han, Sheng Hua; Chen, Jian Xin; Liu, Hong Yan; Zhang, Hai Rong; Ma, Peng Fei; Asian Journal of Chemistry; vol. 27; nb. 4; (2015); p. 1299 - 1303 View in Reaxys With thionyl chloride, Time= 4h, T= 80 °C Fang, Fei; Li, Dong-Dong; Li, Jing-Ran; Sun, Jian; Du, Qian-Ru; Gong, Hai-Bin; Zhu, Hai-Liang; RSC Advances; vol. 3; nb. 48; (2013); p. 26230 - 26240 View in Reaxys With thionyl chloride, Time= 2h, Reflux Li, Xin; Liu, Yan-Hua; Gu, Wen-Jia; Li, Bo; Chen, Fa-Jie; Shi, Bing-Feng; Organic Letters; vol. 16; nb. 15; (2014); p. 3904 - 3907 View in Reaxys With thionyl chloride Hussain, Zaib; Khan, Zulfiqar Ali; Naqvi, Syed Ali Raza; Shahzad, Sohail Anjum; Yar, Muhammad; Hussain, Abdullah Ijaz; Chatha, Shahzad Ali Shahid; Mahmood, Nasir; Khan, Khalid Mohammed; Journal of the Chemical Society of Pakistan; vol. 35; nb. 2; (2013); p. 449 - 455 View in Reaxys 29 General procedure for antagonists synthesis (1, 4a–n) General procedure: A mixture of commercial carboxylic acid in freshly distilled thionyl chloride is warmed into reflux for 2 h, then cooled to room temperature and evaporated under vacuum to dryness to afford quantitatively corresponding acid chlorides (3). This crude material might be used without further purification. A mixture of these acid chloride (1.0 equiv) and ammonium thiocyanate (1.0 equiv) is heated in refluxing dry acetone for 1h. Then, the mixture is cooled to room temperature, and a solution of benzimidazole in dry acetone is carefully added. The mixture is warmed again for 1 h, then cooled to 0 °C, and hydrolyzed with ice. The precipitate is washed with cold water and crude material is crystallized into ethanol. With thionyl chloride, Time= 2h, Reflux Liu, Wang-Qing; Megale, Valentino; Borriello, Lucia; Leforban, Bertrand; Montes, Matthieu; Goldwaser, Elodie; Gresh, Nohad; Piquemal, Jean-Philip; Hadj-Slimane, Reda; Hermine, Olivier; Garbay, Christiane; Raynaud, Francoise; Lepelletier, Yves; Demange, Luc; Bioorganic and Medicinal Chemistry Letters; vol. 24; nb. 17; (2014); p. 4254 - 4259 View in Reaxys With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide Shang, Ming; Wang, Hong-Li; Sun, Shang-Zheng; Dai, Hui-Xiong; Yu, Jin-Quan; Journal of the American Chemical Society; vol. 136; nb. 33; (2014); p. 11590 - 11593 View in Reaxys With thionyl chloride in dichloromethane, Time= 1h, T= 0 - 20 °C Kim, Mirim; Sharma, Satyasheel; Mishra, Neeraj Kumar; Han, Sangil; Park, Jihye; Kim, Minyoung; Shin, Youngmi; Kwak, Jong Hwan; Han, Sang Hoon; Kim, In Su; Chemical Communications; vol. 50; nb. 77; (2014); p. 11303 - 11306 View in Reaxys

23/118

2016-07-02 05:35:12

With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide, Time= 3h, T= 0 - 20 °C , Inert atmosphere Aihara, Yoshinori; Tobisu, Mamoru; Fukumoto, Yoshiya; Chatani, Naoto; Journal of the American Chemical Society; vol. 136; nb. 44; (2014); p. 15509 - 15512 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 1.5h, Inert atmosphere Peixoto, Philippe A.; Boulang, Agathe; Ball, Malcolm; Naudin, Bertrand; Alle, Thibault; Cosette, Pascal; Karuso, Peter; Franck, Xavier; Journal of the American Chemical Society; vol. 136; nb. 43; (2014); p. 15248 - 15256 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 - 20 °C Chen, Zhi-Wei; Zhu, Yi-Zhou; Ou, Jin-Wang; Wang, Ya-Ping; Zheng, Jian-Yu; Journal of Organic Chemistry; vol. 79; nb. 22; (2014); p. 10988 - 10998 View in Reaxys With thionyl chloride in toluene, Time= 1h, T= 80 °C Seth, Kapileswar; Nautiyal, Manesh; Purohit, Priyank; Parikh, Naisargee; Chakraborti, Asit K.; Chemical Communications; vol. 51; nb. 1; (2015); p. 191 - 194 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide in dichloromethane, T= 0 °C , Inert atmosphere Zhang, Shang-Shi; Wu, Jia-Qiang; Lao, Ye-Xing; Liu, Xu-Ge; Liu, Yao; Lv, Wen-Xin; Tan, Dong-Hang; Zeng, Yao-Fu; Wang, Honggen; Organic Letters; vol. 16; nb. 24; (2014); p. 6412 - 6415 View in Reaxys With thionyl chloride, Time= 0.5h, Inert atmosphere, Reflux Dressel, Christian; Liu, Feng; Prehm, Marko; Zeng, Xiangbing; Ungar, Goran; Tschierske, Carsten; Angewandte Chemie - International Edition; vol. 53; nb. 48; (2014); p. 13115 - 13120; Angew. Chem.; vol. 126; nb. 48; (2014); p. 13331 - 13336,6 View in Reaxys With thionyl chloride, Time= 1h, Reflux Zhang, Yi-Ying; Liu, Yuan; Wang, Yu-Liang; Asian Journal of Chemistry; vol. 27; nb. 2; (2015); p. 491 - 495 View in Reaxys With oxalyl dichloride in dichloromethane, Time= 2h, T= 20 °C Sakurai, Kaori; Takeshita, Tomoya; Hiraizumi, Masato; Yamada, Rika; Organic Letters; vol. 16; nb. 24; (2014); p. 6318 - 6321 View in Reaxys With thionyl chloride, Time= 2h, Reflux Liu, Yue-Jin; Liu, Yan-Hua; Yin, Xue-Song; Gu, Wen-Jia; Shi, Bing-Feng; Chemistry--A European Journal; vol. 21; nb. 1; (2015); p. 205 - 209 View in Reaxys With thionyl chloride, Reflux Agrawal, Yogesh P.; Agrawal, Mona Y.; Gupta, Arun K.; Chemical Biology and Drug Design; vol. 85; nb. 2; (2015); p. 172 - 180 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane Wang, Hong-Li; Shang, Ming; Sun, Shang-Zheng; Zhou, Zeng-Le; Laforteza, Brian N.; Dai, Hui-Xiong; Yu, JinQuan; Organic Letters; vol. 17; nb. 5; (2015); p. 1228 - 1231 View in Reaxys General synthetic procedure for compounds 3780 and 9a-e

24/118

2016-07-02 05:35:12

General procedure: To a solution ofcorresponding aromatic carboxylic acid (0.88 mmol) in 5 mL dichloromethane at0 °C was added three drops of DMF. Oxalyl chloride (0.17 g, 1.32 mmol) wasadded dropwise. The mixture was stirred for 1 h at room temperaturethen solvent was removed in vacuo.The resultant oil was dissolved in 3 mLdichloromethane and this solution was added to a solution of 11 (0.2 g, 0.59mmol) and triethylamine (0.17 mL, 0.12 g, 1.18 mmol) in 3 mL dichloromethane at0 °C.The mixture was allowed to warm to room temperature overnight (14 h). Themixture was washed with purified water and saturated salt water. The organiclayer was dried over sodium sulfate and concentrated in vacuo. The resultedresidue was chromatographed on silica gel eluting with CH2Cl2/MeOH(60/1) to give the desired compounds 3780 and 9a-e as white solid. With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 1h, T= 0 - 20 °C Xing, Junhao; Yang, Lingyun; Li, Hui; Li, Qing; Zhao, Leilei; Wang, Xinning; Zhang, Yuan; Zhou, Muxing; Zhou, Jinpei; Zhang, Huibin; European Journal of Medicinal Chemistry; vol. 95; (2015); p. 388 - 399 View in Reaxys General procedure: Aralkanoic acid chlorides 2a-g were synthesized by the reaction of aralkanoic acid 1a-g (1 mmol) in the presence of 1,2-dichloroethane (12 mL) solvent and phosphorous oxychloride(0.4 mL) chlorinating agent under reflux for 3hours. Then, the resulting solution was cooled to room temperature, and the solvent was removed under reduced pressureto afford aralkanoic acid chloride 2a-g, which was directly used in the next step without further purification. Acid chloride 2a-g was dissolved in acetonitrile (80 mL), addeddropwise to a solution containing hydrazine hydrate(1 mmol), TEA (0.5 mL) and acetonitrile (20 mL) and allowed to reflux for 3 hours with monitoring by TLC. After consumption of the starting material, the reaction mixture was cooled to room temperature. Evaporation of the solvent under reduced pressure yielded crude acid hydrazide 3a-g as a white solid on cooling, which was purified by column chromatography and crystallized in methanol [46]. With trichlorophosphate in 1,2-dichloro-ethane, Time= 3h, Reflux Saleem, Muhammad; Yu, Seon-Mi; Rafiq, Muhammad; Kim, Song-Ja; Seo, Sung-Yum; Lee, Ki Hwan; Medicinal Chemistry; vol. 10; nb. 8; (2014); p. 810 - 823 View in Reaxys 2.1.5. General Procedures for the Synthesis of Compounds7a-h General procedure: A mixture of benzoic acid (0.67 g, 0.0055 mol) in thionylchloride (5 mL) was stirred under refluxed for 2h. Aftercooling to room temperature, the mixture was concentratedin vacuo to give crude product benzoyl chloride as a brownoil, which was dissolved in dry CH2Cl2 (10 mL) without furtherpurification. With thionyl chloride, Time= 2h, Reflux Lu, Xiaoyun; Tang, Jian; You, Qidong; Wan, Baojie; Franzblau, Scott G.; Letters in Drug Design and Discovery; vol. 12; nb. 1; (2015); p. 29 - 37 View in Reaxys 4 : 4.2. General procedure for the synthesis of piperazines 2, 4a-k and 10a-f General procedure: 4.2.1. Method i Benzoic acid (1 mmol) was reacted with a solution of thionyl chloride in CH2Cl2 (1 M, 6 mL) in refluxing toluene (3 mL) for 5 h. After cooling to room temperature, the solvent was evaporated under reduced pressure. The obtained benzoyl chloride was dissolved in dry CH2Cl2 (5 mL), and the resultant solution was cooled to 0 C. To this solution, TEA (4.4 mmol, 0.444 g), 1-(9H-fluoren-9-yl)-piperazine (3) (1.1 mmol, 0.275 g) or 1(diphenylmethyl)-piperazine (9) (1.1 mmol, 0.277 g) in dry CH2Cl2 (5 mL) was added dropwise. After the addition, the reaction mixture was stirred for 16 h at room temperature. Subsequently, the solution was washed with aqueous HCl (10percent, v/v, 3 15 mL), a saturated NaHCO3 solution(1 15 mL), and aqueous NaCl (5percent, w/v, 1 15 mL). Finally, the organic layer was dried over anhydrous magnesium sulfate. The mixture was filtered, and the solvent was evaporated under reduce pressure. When necessary, the products were purified using silica gel chromatography with CH2Cl2/methanol (20:5, v/v) as the mobile phase. This protocol was used for the synthesis of 9H-fluoren-9-ylpiperazines 2, 4a, 4c-e, 4h-i and 1-(diphenylmethyl)-piperazines 10a-b and 10d-e. The crystal used for the data collection was obtained by recrystallization of compound 4d from hexane followed by slow evaporation at room temperature. With thionyl chloride in dichloromethane, toluene, Time= 5h, T= 110 °C Rotta, Mariane; Pissinate, Kenia; Villela, Anne Drumond; Back, Davi Fernando; Timmers, Luis Fernando Saraiva Macedo; Bachega, Jos Fernando Ruggiero; De Souza, Osmar Norberto; Santos, Digenes Santiago; Basso, Luiz Augusto; Machado, Pablo; European Journal of Medicinal Chemistry; vol. 90; (2015); p. 436 - 447 View in Reaxys

25/118

2016-07-02 05:35:12

With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 2h, T= 20 °C Damio, Mariana C. F. C. B.; Pasqualoto, Kerly F. M.; Ferreira, Adilson K.; Teixeira, Sarah F.; Azevedo, Ricardo A.; Barbuto, Jos A. M.; Palace-Berl, Fanny; Franchi-Junior, Gilberto C.; Nowill, Alexre E.; Tavares, Maurcio T.; Parise-Filho, Roberto; Archiv der Pharmazie; vol. 347; nb. 12; (2014); p. 885 - 895 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 °C , Inert atmosphere Wang, Shan; Guo, Rui; Wang, Gao; Chen, Shan-Yong; Yu, Xiao-Qi; Chemical Communications; vol. 50; nb. 84; (2014); p. 12718 - 12721 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 5h, T= 0 - 20 °C , Inert atmosphere Ye, Xiaohan; Petersen, Jeffrey L.; Shi, Xiaodong; Chemical Communications; vol. 51; nb. 37; (2015); p. 7863 7866 View in Reaxys General synthesis method of 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole (10ae12h) General procedure: The first method: the starting materials (acids aeh) for thesynthesis of amides should be activated. The compounds aeh(1.0 mM) and SOCl2 (6 - 10 mL) were mixed and stirred at reflux80 C for 4 h, then cooled and evaporated to give reactive acylchloride, respectively. A solution of acyl chloride (1.0 mM) in ethylacetate (5 - 6 mL) was added dropwise to the corresponding suspensionof amine compounds (10e12) (0.5 mM) and triethylamine(0.5 mL) in 20 mL ethyl acetate at 0 C. After stirring overnight, thereaction mixture was then poured in excess of diluted NaOH andextracted with EtOAc. The extraction liquid was purified by a flashchromatography with EtOAc/ petroleum ether (3:1, v/v) to give 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole (10ae12h), ayellow or white powder, respectively with yields of 40percente85percent. With thionyl chloride, Time= 4h, T= 80 °C Wang, Yan-Ting; Qin, Ya-Juan; Yang, Na; Zhang, Ya-Liang; Liu, Chang-Hong; Zhu, Hai-Liang; European Journal of Medicinal Chemistry; vol. 99; (2015); p. 125 - 137 View in Reaxys With thionyl chloride, Time= 3h, T= 85 °C , Inert atmosphere Barsu, Nagaraju; Kalsi, Deepti; Sundararaju, Basker; Chemistry - A European Journal; vol. 21; nb. 26; (2015); p. 9364 - 9368 View in Reaxys 4.1. General procedure for the synthesis of carboxylic amides General procedure: To a solution of carboxylic acid (5 mmol) in CH2Cl2 (10 mL) were added oxalyl chloride (0.5 mL, 6 mmol, 1.2 equiv.) and DMF (two drops) at 0 °C. The mixture was stirred until gas evolution stopped. Then it was concentrated under reduced pressure, washed with dichloromethane and concentrated again. The crude acyl chloride was used directly in the next step. With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 °C , Inert atmosphere, Schlenk technique Li, Xijing; Zou, Gang; Journal of Organometallic Chemistry; vol. 794; (2015); p. 136 - 145; Art.No: 19152 View in Reaxys With thionyl chloride, Time= 2h, Reflux De Oliveira, Clara G. M.; Faria, Vitor W.; De Andrade, Gabriel F.; Delia, Eliane; Cabral, Murilo F.; Cotrim, Bruno A.; Resende, Gabriel O.; De Souza, Flvia C.; Phosphorus, Sulfur and Silicon and the Related Elements; vol. 190; nb. 8; (2015); p. 1366 - 1377 View in Reaxys Saeed, Aamer; Ejaz, Syeda Abida; Khurshid, Asma; Hassan, Sidra; Al-Rashida, Mariya; Latif, Muhammad; Lecka, Joanna; Svigny, Jean; Iqbal, Jamshed; RSC Advances; vol. 5; nb. 105; (2015); p. 86428 - 86439 View in Reaxys 4 : 4.2.1. Method i Benzoic acid (1 mmol) was reacted with a solution of thionyl chloride in CH2Cl2 (1 M, 6 mL) in refluxing toluene (3 mL) for 5 h. After cooling to room temperature, the solvent was evaporated under reduced pressure. The obtained

26/118

2016-07-02 05:35:12

benzoyl chloride was dissolved in dry CH2Cl2 (5 mL), and the resultant solution was cooled to 0 °C. To this solution, TEA (4.4 mmol, 0.444 g), 1-(9H-fluoren-9-yl)-piperazine (3) (1.1 mmol, 0.275 g) or 1-(diphenylmethyl)-piperazine (9) (1.1 mmol, 0.277 g) in dry CH2Cl2 (5 mL) was added dropwise. After the addition, the reaction mixture was stirred for 16 h at room temperature. Subsequently, the solution was washed with aqueous HCl (10percent, v/v, 3 x 15 mL), a saturated NaHCO3 solution (1 x 15 mL), and aqueous NaCl (5percent, w/v, 1 x 15 mL). Finally, the organic layer was dried over anhydrous magnesium sulfate. The mixture was filtered, and the solvent was evaporated under reduce pressure. When necessary, the products were purified using silica gel chromatography with CH2Cl2/methanol (20:5, v/v) as the mobile phase. This protocol was used for the synthesis of 9H-fluoren-9-yl-piperazines 2, 4a, 4c-e, 4h-i and 1-(diphenylmethyl)-piperazines 10a-b and 10d-e. The crystal used for the data collection was obtained by recrystallization of compound 4d from hexane followed by slow evaporation at room temperature. With thionyl chloride in dichloromethane, toluene, Time= 5h, T= 110 °C Rotta, Mariane; Pissinate, Kenia; Villela, Anne Drumond; Back, Davi Fernando; Timmers, Luis Fernando Saraiva MacEdo; Bachega, Jos Fernando Ruggiero; De Souza, Osmar Norberto; Santos, Digenes Santiago; Basso, Luiz Augusto; MacHado, Pablo; European Journal of Medicinal Chemistry; vol. 90; (2014); p. 436 - 447 View in Reaxys Method A: General procedure: A solution of acid (5 mmol) in SOCl2 (5 mL) was refluxedfor 2 h and cooled to r.t.. The excess of SOCl2 wasremoved under vacuum to give the corresponding acid chloride.The acid chloride was then re-dissolved in 5 mL anhydrousCH2Cl2 and added dropwise to a 20 mL anhydrousCH2Cl2 solution containing PIP-NH2 (5 mmol) and Et3N (10mmol) at 0 °C. After stirring for 6 h at r.t., the resultingmixture was washed with brine, dried over MgSO4, filteredand concentrated under reduced pressure. The residue waspurified by flash chromatography to give the desired product. With thionyl chloride, Time= 2h, Reflux Zhao, Sheng; Chen, Fa-Jie; Liu, Bin; Shi, Bing-Feng; Science China Chemistry; vol. 58; nb. 8; (2015); p. 1302 1309 View in Reaxys Experimental procedure for the synthesis of 2–9 General procedure: to a solution of the carboxylic acid (2 mmol) and oxalyl chloride (10 mmol) in dried CH2Cl2, 3 drops of dried DMF were added and the reaction mixture was stirred for 30 min under N2 at room temperature. After total consumption of the starting material, solvent was removed. Then, the crude acid chloride was dissolved in dried CH2Cl2 (3–5 mL) and alcohol 14 (1 mmol) and Et3N (2.5 mmol) were added. The reaction mixture was stirred under N2 atmosphere for 12–24 h at room temperature. The reaction mixture was filtered, concentrated and purified by preparative TLC or column chromatography, furnishing the desired ester derivatives. With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 0.5h, T= 20 °C , Inert atmosphere Fernandes, talo A.; De Almeida, Letcia; Ferreira, Patrcia Espuri; Marques, Marcos J.; Rocha, Rassa P.; Coelho, Luiz F.L.; Carvalho, Diogo T.; Viegas, Claudio; Bioorganic and Medicinal Chemistry Letters; vol. 25; nb. 16; (2015); p. 3346 - 3349; Art.No: 22758 View in Reaxys The General Procedures for Synthesis of Benzoyl Chlorides 2 General procedure: To a stirred solution of benzoic acid 1 (3 mmol), SOCl2(0.44 g, 3.75 mmol) was added dropwise. The mixture was heated gently at 100 oC for 1 h, cooled and then distilled(70°C) at atmospheric pressure to remove excess SOCl2. Avacuum was applied, and the residue of liquid benzoyl chlorides2 were used without further purification. With thionyl chloride, Time= 1h, T= 100 °C Zhao, Chengguang; Feng, Jianpeng; Zuo, Mingming; Zhang, Ying; Zhao, Jianfeng; Xu, Shanmei; Zheng, Suqing; Zhang, Yali; Tang, Qinqin; Lu, Zhongqiu; Liang, Guang; Zhou, Jianmin; Medicinal Chemistry; vol. 11; nb. 6; (2015); p. 567 - 572 View in Reaxys With oxalyl dichloride in toluene, T= 0 - 20 °C , Inert atmosphere Wang, Pei-Long; Li, Yan; Wu, Yun; Li, Chao; Lan, Quan; Wang, Xi-Sheng; Organic Letters; vol. 17; nb. 15; (2015); p. 3698 - 3701

27/118

2016-07-02 05:35:12

View in Reaxys A catalytic amount of dry DMF (one drop) was added to a mixture of benzoic acid (1.0 g, 8.18 mmol) and (COCl)2 (1.40 mL,16.4 mmol) in dry CH2Cl2 (50 mL) at 0 °C, under an argon atmosphere. The reaction mixture was left to stir at 0 °C for 30 min then the solvent was evaporated under vacuum. The residual HCl was eliminated by co-evaporation with CHCl3 (10 mL) and toluene (10 mL). The crude acid chloride was dried under vacuum and then dissolved in dry CH2Cl2 (20 mL). The solution was cooled to -78 °C and DIPEA (3.56 mL, 20.4 mmol) was added, followed by propargylamine (0.79 mL, 12.3 mmol). The reaction mixture was left to stir overnight being allowed to warm to rt during this period. The solvent was evaporated under vacuum and the residue was purifiedby column chromatography on silica gel (hexanes/EtOAc 1:1 toEtOAc) to give the product in 89percent yield (1.16 g, 7.28 mmol) as a white solid With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 0.5h, T= 0 °C , Inert atmosphere Carosso, Serena; Miller, Marvin J.; Bioorganic and Medicinal Chemistry; vol. 23; nb. 18; (2015); p. 6138 - 6147 View in Reaxys With thionyl chloride, Inert atmosphere Banerjee, Deb Ranjan; Biswas, Rupam; Das, Amit K.; Basak, Amit; European Journal of Medicinal Chemistry; vol. 100; (2015); p. 223 - 234 View in Reaxys General procedure for the synthesis of the 2-benzoylaminoacetamide and 2-(2-thienoylamino)acetamide derivatives General procedure: 0.02 mol of acid (benzoic acid and 2-thienoic acid) in 5 mL of thionyl chloride were refluxed for 1 h at 80 C and thionyl chloride was evaporated. The crude acid chloride was used in the next step without purification. 0.02 mol of glycine and 0.02 mol of acid chloride were separately dissolved in 15 mL of 2 M sodium hydroxide solution at 0–5 °C. Acid chloride in sodium hydroxide solution was added to glycine solution in portions for 30 min by stirring and cooling. The mixture was stirred for additional 30 min at room temperature. The mixture was acidified by concentrated hydrochloride acid. The precipitated product was filtered and recrystallized from water to obtain hippuric acid (81 percent yield) and 2-(2-thienoylamino)acetic acid (80 percent yield). 0.01 mol of 2-acylamino acetic acid and 0.25 mL of concentrated sulfuric acid in 15 mL of methanol were refluxed for 2 h at 80°C and the excess of methanol was evaporated. The residue was extracted by chloroform (3 9 30 mL). The chloroform phase was washed by 20 mL of 1 M sodium hydroxide solution and dried over anhydrous sodium sulfate. Chloroform was evaporated, and the residue was recrystallized from ethyl acetate to obtain methyl hippurate (84 percent yield) and methyl 2-(2thienoylamino)acetate (70 percent yield). 0.005 mol of methyl ester and 0.03 mol of appropriate amine in 5 mL of methanol were refluxed for 4 h at 80 °C. After the reaction was completed, the excess of solvent was evaporated. The compounds were purified by column chromatography [CHCl3:MeOH (11:1)] and then crystallized with an appropriate solvent. With thionyl chloride, Time= 1h, T= 80 °C Coban, Gunes; Kose, Fadime Aydin; Kirmizibayrak, Petek Ballar; Pabuccuoglu, Varol; Medicinal Chemistry Research; vol. 24; nb. 10; (2015); p. 3710 - 3729 View in Reaxys General synthetic procedure for compounds 8-11 and 13-36 General procedure: To a stirred suspension of various carboxylic acid 4a, 4b, 6a and 8a (1.0 equiv) in CH2Cl2 (25 mL) was added oxalyl chloride (3.0 equiv) and a catalytic amount of DMF. After stirring at room temperature for 3 h, the reaction was concentrated under reduced pressure to afford a yellow oil crude acyl chloride. To a solution of methyl 2-(4-amino-2-fluorophenoxy)acetate 3a (1.0 equiv) in CH2Cl2(25 mL) was added Et3N (1.5 equiv), and this mixture was cooled to −5 °C. Subsequently, the crude acyl chloride obtained above was added in dropwise at a rate to ensure that the temperature did not exceed 0 °C. The solution was stirred for another 2 hrs at 25 °C, then washed successively with 10percent HCl (2 × 25 mL), 10percent NaHCO3 (2 × 25 mL) and brine (2 × 20 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and the solvent was then evaporated to give the impure amide which was recrystallized from ethanol to give the desired products as colorless crystals. To a solution of the obtained crystals (1.0 equiv)in 2:3:1 THF/MeOH/H2O (18 ml) was added LiOH·H2O (1.5 equiv). After stirring at room temperature for 4 h, the volatiles were removed under reduced pressure. The residue was acidified with 1N hydrochloric acid solution, and then filtered and the filter cake was washed with 5 mL of water, dried in vacuum to afford a white powder. Recrystallization from 75percent EtOH gave the desired compounds 8-11 and 13-36 as colorless crystals. With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 3h, T= 20 °C

28/118

2016-07-02 05:35:12

Li, Zheng; Wang, Xuekun; Xu, Xue; Yang, Jianyong; Qiu, Qianqian; Qiang, Hao; Huang, Wenlong; Qian, Hai; Bioorganic and Medicinal Chemistry; vol. 23; nb. 20; (2015); p. 6666 - 6672 View in Reaxys With thionyl chloride in butan-1-ol, T= 55 - 60 °C , Inert atmosphere Easwaramoorthi; Rajendran, A. Jeya; Rao, K. Chennakesava; Arun; Balachandran; Perumal; Emi, Nobuhiko; Mahalingam; Duraipandiyan; Al-Dhabi; RSC Advances; vol. 5; nb. 127; (2015); p. 105266 - 105278 View in Reaxys With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide, T= 0 °C He, Haifeng; Feng, Jiangtao; He, Junbo; Xia, Qin; Ren, Yanliang; Wang, Fang; Peng, Hao; He, Hongwu; Feng, Lingling; RSC Advances; vol. 6; nb. 6; (2016); p. 4310 - 4320 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 5h, T= 0 °C , Inert atmosphere Cera, Gianpiero; Haven, Tobias; Ackermann, Lutz; Angewandte Chemie - International Edition; vol. 55; nb. 4; (2016); p. 1484 - 1488 View in Reaxys With thionyl chloride in dichloromethane, Time= 2 - 3h, T= 90 °C Senger, Johanna; Melesina, Jelena; Marek, Martin; Romier, Christophe; Oehme, Ina; Witt, Olaf; Sippl, Wolfgang; Jung, Manfred; Journal of Medicinal Chemistry; vol. 59; nb. 4; (2016); p. 1545 - 1555 View in Reaxys With thionyl chloride Zheng, Jing; Deng, Ziyang; Zhang, Yan; Cui, Sunliang; Advanced Synthesis and Catalysis; vol. 358; nb. 5; (2016); p. 746 - 751 View in Reaxys 2.1.1. Synthesis of substituted benzohydrazide. (4a-4g) General procedure: Substituted benzoic acid (1.0 mmol) was dissolved in thionylchloride and refluxed for 2 h, then the solvent was removed underreduced pressure to obtain the white solid. The white solid in methanol was added concentrated sulfuric acid (1 mL) and themixture was refluxed for 4 h, the solvent was removed to obtaincrude solid. The crude solid was extracted with ethyl acetate andwater. The solvents were evaporated to afford the pure product.Finally, the pure product was dissolved in ethanol, and the hydrazinehydrate was added. The mixture was refluxed for 9 h, and thesolvent was removed With thionyl chloride, Time= 2h, Reflux Lian, Zhi-Min; Sun, Juan; Zhu, Hai-Liang; Journal of Molecular Structure; vol. 1117; (2016); p. 8 - 16 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 °C , Inert atmosphere, Schlenk technique Gandeepan, Parthasarathy; Rajamalli, Pachaiyappan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 55; nb. 13; (2016); p. 4308 - 4311; Angew. Chem.; vol. 128; (2016); p. 4380 - 4383,4 View in Reaxys With thionyl chloride, Time= 0.5h, T= 85 °C , Reflux Wu, Youzhi; Sun, Peng; Zhang, Kaifan; Yang, Tie; Yao, Hequan; Lin, Aijun; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 2166 - 2173 View in Reaxys With thionyl chloride, Time= 1h, Inert atmosphere, Reflux Laurell Nash, Anna; Hertzberg, Robin; Wen, Ye-Qian; Dahlgren, Björn; Brinck, Tore; Moberg, Christina; Chemistry - A European Journal; vol. 22; nb. 11; (2016); p. 3821 - 3829 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 3h, T= 0 - 20 °C

29/118

2016-07-02 05:35:12

Zhang, Lanlan; Geng, Yu; Jin, Zhong; Journal of Organic Chemistry; vol. 81; nb. 9; (2016); p. 3542 - 3552 View in Reaxys With thionyl chloride, T= 80 °C Jiao, Yan; Li, Ming; Wang, Ning; Lu, Tao; Zhou, Liang; Huang, Yan; Lu, Zhiyun; Luo, Daibing; Pu, Xuemei; Journal of Materials Chemistry C; vol. 4; nb. 19; (2016); p. 4269 - 4277 View in Reaxys O 13C

O 13C

Rx-ID: 2064775 View in Reaxys 3/294 Yield 99.9 %

Conditions & References With phosphorus pentachloride, Time= 1.5h, T= 60 °C Seebach, Dieter; Haessig, Robert; Gabriel, Jozef; Helvetica Chimica Acta; vol. 66; nb. 1; (1983); p. 308 - 337 View in Reaxys

95 %

With thionyl chloride Clark, Adrian D.; Janowski, Wit K.; Prager, Rolf H.; Tetrahedron; vol. 55; nb. 12; (1999); p. 3637 - 3648 View in Reaxys

92 %

With thionyl chloride in dichloromethane, 1.) 4 h, reflux, 2.) 35 degC Cywar, Douglas A.; Tirrell, David A.; Journal of the American Chemical Society; vol. 111; nb. 19; (1989); p. 7544 7553 View in Reaxys

77 %

With thionyl chloride, Time= 3h, Heating Casey, Charles P.; Scheck, Daniel M.; Journal of the American Chemical Society; vol. 102; nb. 8; (1980); p. 2728 2731 View in Reaxys With thionyl chloride Knaap, Th.A. van der; Klebach, Th.C.; Visser, F.; Bickelhaupt, F.; Ros, P.; et al.; Tetrahedron; vol. 40; nb. 4; (1984); p. 765 - 776 View in Reaxys Takeuchi, Ken'ichi; Murai, Osamu; Matsui, Shin; Inoue, Takeshi; Kitagawa, Toshikazu; Okamoto, Kunio; Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999); nb. 9; (1983); p. 1301 1310 View in Reaxys Matsushita, Michio; Nakamura, Toshihiro; Momose, Takamasa; Shida, Tadamasa; Teki, Yoshio; Takui, Takeji; Kinoshita, Takamasa; Itoh, Koichi; Journal of the American Chemical Society; vol. 114; nb. 19; (1992); p. 7470 7475 View in Reaxys With thionyl chloride in benzene, Time= 3h, Heating Brown, John M.; Chaloner, Penny A.; Journal of the American Chemical Society; vol. 102; nb. 9; (1980); p. 3040 3048 View in Reaxys With thionyl chloride Dao,L.H.; Malecki,M.; Hopkinson,A.C.; Journal of the American Chemical Society; vol. 108; (1986); p. 5237 View in Reaxys With thionyl chloride, Time= 6h, Heating, Substitution Nakagaki, Ryoichi; Yamaoka, Masaharu; Mutai, Kiyoshi; Bulletin of the Chemical Society of Japan; vol. 72; nb. 3; (1999); p. 347 - 355 View in Reaxys

30/118

2016-07-02 05:35:12

With thionyl chloride, Time= 1h, Heating Wu, Gang; Dong, Shuan; Chemical Physics Letters; vol. 334; nb. 4-6; (2001); p. 265 - 270 View in Reaxys With thionyl chloride in tetrahydrofuran, Time= 48h, T= 20 °C Xi, Zhenfeng; Sato, Kimihiko; Gao, Ye; Lu, Jianming; Takahashi, Tamotsu; Journal of the American Chemical Society; vol. 125; nb. 32; (2003); p. 9568 - 9569 View in Reaxys Reaction Steps: 2 1: TiCl4, NaBH4 / bis-(2-methoxy-ethyl) ether / 16 h / Ambient temperature 2: Ph3PCl2 / CH2Cl2 / 24 h / Ambient temperature With sodium tetrahydroborate, titanium tetrachloride, Ph3PCl(+)Cl(-) in dichloromethane, diethylene glycol dimethyl ether Katritzky, Alan R.; Voronkov, Michael V.; Toader, Dorin; Journal of the Chemical Society. Perkin Transactions 2; nb. 11; (1998); p. 2515 - 2518 View in Reaxys With thionyl chloride, Time= 1h, Inert atmosphere, Reflux Bichler, Paul; Chalifoux, Wesley A.; Eisler, Sara; Shi Shun, Annabelle L. K.; Chernick, Erin T.; Tykwinski, Rik R.; Organic Letters; vol. 11; nb. 3; (2009); p. 519 - 522 View in Reaxys With thionyl chloride in dichloromethane, Inert atmosphere Tykwinski, Rik R.; Luu, Thanh; Synthesis (Germany); vol. 44; nb. 12; (2012); p. 1915 - 1922; Art.No: SS-2012Z0165-OP View in Reaxys With thionyl chloride in dichloromethane, Time= 8h, Reflux, Inert atmosphere Servos, Mark A.; Smart, Nathaniel C.; Kassabaum, Mark E.; Scholtens, Cody A.; Peters, Steven J.; Journal of Organic Chemistry; vol. 78; nb. 8; (2013); p. 3908 - 3917 View in Reaxys With thionyl chloride, Time= 3h, Reflux Adcock, Holly V.; Langer, Thomas; Davies, Paul W.; Chemistry - A European Journal; vol. 20; nb. 24; (2014); p. 7262 - 7266 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 0.5h, T= 0 °C Shiroodi, Kazem Roohollah; Sugawara, Masumi; Ratushnyy, Maxim; Yarbrough, Douglas C.; Wink, Donald J.; Gevorgyan, Vladimir; Organic Letters; vol. 17; nb. 16; (2015); p. 4062 - 4065 View in Reaxys O

H 13C 13

13CH

H 13C 13CH

H 13C 13

CH 13

H 13C 13CH

Rx-ID: 3708071 View in Reaxys 4/294 Yield

Conditions & References With oxalyl dichloride, DMFA in dichloromethane, Time= 3h, Ambient temperature Ares; Wehmeyer; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 34; nb. 7; (1994); p. 635 - 641 View in Reaxys With thionyl chloride in benzene, Time= 3h, Heating, Chlorination Breuer, Stephen W.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 43; nb. 3; (2000); p. 283 286

31/118

2016-07-02 05:35:12

View in Reaxys With thionyl chloride in benzene, Time= 5h, Reflux Latli, Bachir; Hrapchak, Matt; Easter, John A.; Stolle, Wayne T.; Grozinger, Karl; Krishnamurthy, Dhileepkumar; Senanayake, Chris H.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 51; nb. 8; (2008); p. 314 - 320 View in Reaxys Thionyl chloride (2 mL) was added to benzoyl-1,2,3,4,5,6-13C6 acid (311 mg, 2.4 mmol) under argon atm. The reaction was warmed to 65 °C for 2 h. The excess reagent was evaporated under vacuum. To the crude benzoyl-1,2,3,4,5,6-13C6 chloride was added pyridine (2 mL), and the reagent was added slowly to a stirred solution of (−)-methylecgonine hydrochloride (413 mg, 1.8 mmol) in pyridine (5 mL) at 0 °C. The resulting solution was stirred at ambient temperature for 24 h and then cooled to 10 °C. The cooled solution was added to saturated solution of sodium bicarbonate, and the pyridine was removed under vacuum; then, toluene was added (5 mL) and evaporated. Water (20 mL) and ammonium hydroxide was added until the pH of the combined aqueous solution was 9. After the pH adjustment, the combined aqueous solution was extracted twice with chloroform (2 × 20 mL). The water phase can be acidified and cooled to precipitate unused benzoyl-1,2,3,4,5,6-13C6 acid. The combined chloroform extracts were dried over sodium carbonate, filtered and evaporated to yield a yellow oil. The oil was dissolved in tert-butyl methyl ether (10 mL), stirred with silica-gel (0.1 g), filtered and dried in a vacuum to give the product [13C6]-7 as a clear oil. This was dissolved in diethyl ether, and HCl × isopropanol (5.5 M) was added until pH 4. The solid salt was filtered and washed with diethyl ether and recrystallized from ethanol and diethyl ether. The second crop of crystals was isolated upon concentration of the mother liquor. The total yield of the hydrochloride of [13C6]-7 was 362 mg (1.05 mmol, 59percent) with a purity of 99percent (HPLC). With thionyl chloride, Time= 2h, T= 65 °C , Inert atmosphere Karlsen, Morten; Liu, Huiling; Johansen, Jon Eigill; Hoff, Bård Helge; Molecules; vol. 20; nb. 4; (2015); p. 5329 - 5345 View in Reaxys O

Rx-ID: 817417 View in Reaxys 5/294 Yield

Conditions & References With chlorine, T= 130 - 150 °C , anschliessendes Erhitzen auf 190-200grad Patent; Imp. Chem. Ind.; US1851832; (1928) View in Reaxys Patent; Imp. Chem. Ind.; DE548131; (1928); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 18; p. 529 View in Reaxys 29 : 2,3-Dichloro-4-(p-nitrophenoxy)phenylacetonitrile This alcohol (20 g., 0.064 mole) was dissolved in 150 ml. of chloroform and 18.7 ml. of thionyl chloride was added. After the solution had been stirred for 5 hours at room temperature, the solvent was evaporated to give 21.1 g. of benzylic chloride. NMR (CDCl3): 4.70 (2H, s, ArCH2 Cl). With thionyl chloride in chloroform Patent; Abbott Laboratories; US4389416; (1983); (A1) English View in Reaxys With trichloroisocyanuric acid in dichloromethane, Time= 120h, T= 20 °C , Inert atmosphere Gaspa, Silvia; Porcheddu, Andrea; De Luca, Lidia; Advanced Synthesis and Catalysis; vol. 358; nb. 1; (2016); p. 154 - 158 View in Reaxys

Rx-ID: 2036306 View in Reaxys 6/294

32/118

2016-07-02 05:35:12

Yield 82 %

Conditions & References With thionyl chloride, Time= 1h, Heating, Substitution Gomis, Jean-Marie; Santolini; Andre; Noel; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. 12; (1999); p. 1175 - 1182 View in Reaxys

80 %

With thionyl chloride in benzene, Time= 8h, Heating Roshchupkina, Galina A.; Pervukhina, Natalie V.; Rybalova, Tatjana V.; Gatilov, Yuri V.; Burdukov, Alexey B.; Reznikov, Vladimir A.; European Journal of Organic Chemistry; nb. 22; (2003); p. 4432 - 4437 View in Reaxys With thionyl chloride, Time= 3h, Heating Hege; Weymann; Lietz; Arzneimittel-Forschung/Drug Research; vol. 34; nb. 8; (1984); p. 843 - 849 View in Reaxys With thionyl chloride Yamataka, Hiroshi; Nagareda, Katsushi; Takatsuka, Tsutomu; Ando, Katsuhiro; Hanafusa, Terukiyo; Nagase, Shigeru; Journal of the American Chemical Society; vol. 115; nb. 19; (1993); p. 8570 - 8576 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in toluene, Time= 70h, T= 20 °C Kuo, Fengjiun; Clodfelter, Dean K.; Wheeler, William J.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 47; nb. 9; (2004); p. 615 - 625 View in Reaxys With thionyl chloride in benzene, Time= 3h, Reflux Latli, Bachir; Hrapchak, Matt; Easter, John A.; Stolle, Wayne T.; Grozinger, Karl; Krishnamurthy, Dhileepkumar; Senanayake, Chris H.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 51; nb. 8; (2008); p. 314 - 320 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 3h, Inert atmosphere Elmore, Charles S.; Dorff, Peter N.; Powell, Mark E.; Hall, James E.; Simpson, Thomas R.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 54; nb. 5; (2011); p. 239 - 246 View in Reaxys

18O

H 18O

Yield

Conditions & References

Rx-ID: 9071553 View in Reaxys 7/294 85 %

59 %

With phosphorus pentachloride, Time= 1h, T= 60 °C Haiss, Peter; Zeller, Klaus-Peter; Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences; vol. 58; nb. 6; (2003); p. 595 - 605 View in Reaxys With oxalyl dichloride, Time= 1h, T= 77 °C Haiss, Peter; Zeller, Klaus-Peter; Angewandte Chemie - International Edition; vol. 42; nb. 3; (2003); p. 303 - 305 View in Reaxys With thionyl chloride, Time= 1h, T= 90 °C , Sealed tube

33/118

2016-07-02 05:35:12

Hu, Yancheng; Yi, Ruxia; Yu, Xinzhang; Xin, Xiaoyi; Wang, Chunxiang; Wan, Boshun; Chemical Communications; vol. 51; nb. 84; (2015); p. 15398 - 15401 View in Reaxys O

Rx-ID: 40637 View in Reaxys 8/294 Yield

Conditions & References With phosphorus pentachloride, T= 160 - 180 °C Authenrieth; Muehlinghaus; Chemische Berichte; vol. 40; (1907); p. 748 View in Reaxys With chlorine Patent; California Research Corp.; US2865959; (1955) View in Reaxys Acid chlorides preparation 2 General procedure: Acetylated acids (10 mmol) were taken in dried CHCl3 (20 ml). To that DMF (200 l) and SOCl2 (13 mmol) was added. Refluxed for 1-2 h (monitored by TLC, solvent; ethyl acetate 7: petroleum ether 3). Solvent was removed under reduced pressure. Acid chloride used for esterification reaction. With thionyl chloride in chloroform, N,N-dimethyl-formamide, Reflux Pandurangan; Letters in Organic Chemistry; vol. 11; nb. 3; (2014); p. 225 - 229 View in Reaxys 2H

O 2H

HO 2

Rx-ID: 4161237 View in Reaxys 9/294 Yield 92 %

Conditions & References With thionyl chloride, sodium chloride, Heating, Substitution Everhart, E. Thomas; Jacob III, Peyton; Mendelson, John; Jones, Reese T.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 42; nb. 13; (1999); p. 1265 - 1275 View in Reaxys

83 %

With thionyl chloride, Time= 1.5h, Reflux Hetayothin, Boonta; Cabaniss, Roy A.; Blum, Frank D.; Macromolecules; vol. 45; nb. 22; (2012); p. 9128 - 9138 View in Reaxys With thionyl chloride Vrielynck, L.; Cornard, J. P.; Merlin, J. C.; Lautie, M. F.; Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy; vol. 50; nb. 13; (1994); p. 2177 - 2188 View in Reaxys With thionyl chloride, Time= 6h, Heating, Substitution Nakagaki, Ryoichi; Yamaoka, Masaharu; Mutai, Kiyoshi; Bulletin of the Chemical Society of Japan; vol. 72; nb. 3; (1999); p. 347 - 355 View in Reaxys With thionyl chloride, Time= 4h, Heating Domenici; Madsen; Choi; Samulski; Veracini; Chemical Physics Letters; vol. 402; nb. 4-6; (2005); p. 318 - 323 View in Reaxys With thionyl chloride in DMFA, Time= 1h, T= 80 °C , Inert atmosphere

34/118

2016-07-02 05:35:12

Ackermann, Lutz; Lygin, Alexander V.; Hofmann, Nora; Angewandte Chemie - International Edition; vol. 50; nb. 28; (2011); p. 6379 - 6382 View in Reaxys With oxalyl dichloride, DMFA in dichloromethane, Time= 4h, T= 0 - 20 °C , Inert atmosphere Grohmann, Christoph; Wang, Honggen; Glorius, Frank; Organic Letters; vol. 14; nb. 2; (2012); p. 656 - 659 View in Reaxys With oxalyl dichloride in tetrahydrofuran, DMFA, T= 0 - 20 °C , Inert atmosphere Wencel-Delord, Joanna; Nimphius, Corinna; Patureau, Frederic W.; Glorius, Frank; Angewandte Chemie - International Edition; vol. 51; nb. 9; (2012); p. 2247 - 2251 View in Reaxys With oxalyl dichloride, DMFA in dichloromethane, T= 0 - 20 °C , Inert atmosphere Wang, Honggen; Glorius, Frank; Angewandte Chemie - International Edition; vol. 51; nb. 29; (2012); p. 7318 7322 View in Reaxys With oxalyl dichloride, DMFA in dichloromethane, Time= 4h, T= 20 °C , Inert atmosphere Zhang, Nana; Li, Binyao; Zhong, Hongban; Huang, Jianhui; Organic and Biomolecular Chemistry; vol. 10; nb. 47; (2012); p. 9429 - 9439 View in Reaxys With oxalyl dichloride, DMFA in dichloromethane, T= 0 - 20 °C , Inert atmosphere, Schlenk technique Karthikeyan, Jaganathan; Haridharan, Radhakrishnan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 51; nb. 49; (2012); p. 12343 - 12347; Angew. Chem.; vol. 124; nb. 49; (2012); p. 12509 - 12513,4 View in Reaxys With thionyl chloride in dichloromethane, Time= 8h, Reflux, Inert atmosphere Servos, Mark A.; Smart, Nathaniel C.; Kassabaum, Mark E.; Scholtens, Cody A.; Peters, Steven J.; Journal of Organic Chemistry; vol. 78; nb. 8; (2013); p. 3908 - 3917 View in Reaxys With oxalyl dichloride in dichloromethane, DMFA, Reflux Suess, Alison M.; Ertem, Mehmed Z.; Cramer, Christopher J.; Stahl, Shannon S.; Journal of the American Chemical Society; vol. 135; nb. 26; (2013); p. 9797 - 9804 View in Reaxys With oxalyl dichloride, DMFA in dichloromethane, Time= 4h, T= 20 °C , Inert atmosphere Senthilkumar, Natarajan; Parthasarathy, Kanniyappan; Gandeepan, Parthasarathy; Cheng, Chien-Hong; Chemistry - An Asian Journal; vol. 8; nb. 9; (2013); p. 2175 - 2181 View in Reaxys With thionyl chloride in dichloromethane, DMFA, Time= 2h, Reflux Li, Xin; Liu, Yan-Hua; Gu, Wen-Jia; Li, Bo; Chen, Fa-Jie; Shi, Bing-Feng; Organic Letters; vol. 16; nb. 15; (2014); p. 3904 - 3907 View in Reaxys With oxalyl dichloride, DMFA in dichloromethane, Time= 5h, T= 0 - 20 °C , Inert atmosphere, Schlenk technique Prakash, Sekar; Muralirajan, Krishnamoorthy; Cheng, Chien-Hong; Chemical Communications; vol. 51; nb. 69; (2015); p. 13362 - 13364 View in Reaxys With thionyl chloride Zheng, Jing; Deng, Ziyang; Zhang, Yan; Cui, Sunliang; Advanced Synthesis and Catalysis; vol. 358; nb. 5; (2016); p. 746 - 751

35/118

2016-07-02 05:35:12

View in Reaxys With oxalyl dichloride, DMFA in dichloromethane, Time= 4h, T= 20 °C , Inert atmosphere, Schlenk technique Gandeepan, Parthasarathy; Rajamalli, Pachaiyappan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 55; nb. 13; (2016); p. 4308 - 4311; Angew. Chem.; vol. 128; (2016); p. 4380 - 4383,4 View in Reaxys 17O

H 17O

Yield

Conditions & References

Rx-ID: 8710705 View in Reaxys 10/294 80 %

With thionyl chloride, Time= 1h, T= 100 °C Wnuk, Stanislaw F.; Chowdhury, Saiful M.; Garcia Jr., Pedro I.; Robins, Morris J.; Journal of Organic Chemistry; vol. 67; nb. 6; (2002); p. 1816 - 1819 View in Reaxys With thionyl chloride, Time= 1h, Heating Wu, Gang; Dong, Shuan; Chemical Physics Letters; vol. 334; nb. 4-6; (2001); p. 265 - 270 View in Reaxys With thionyl chloride, Heating, Chlorination Wu, Gang; Yamada, Kazuhiko; Dong, Shuan; Grondey, Hiltrud; Journal of the American Chemical Society; vol. 122; nb. 17; (2000); p. 4215 - 4216 View in Reaxys With thionyl chloride, Time= 1h, Heating Yamada, Kazuhiko; Dong, Shuan; Wu, Gang; Journal of the American Chemical Society; vol. 122; nb. 47; (2000); p. 11602 - 11609 View in Reaxys

O HO

Cl 2H

Rx-ID: 31325787 View in Reaxys 11/294 Yield

Conditions & References With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, T= 0 - 20 °C , Inert atmosphere Shacklady-Mcatee, Danielle M.; Dasgupta, Srimoyee; Watson, Mary P.; Organic Letters; vol. 13; nb. 13; (2011); p. 3490 - 3493 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 3.03333h, T= 0 - 20 °C Zeng, Rong; Fu, Chunling; Ma, Shengming; Journal of the American Chemical Society; vol. 134; nb. 23; (2012); p. 9597 - 9600 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 4h, T= 0 - 20 °C , Inert atmosphere, Schlenk technique Karthikeyan, Jaganathan; Haridharan, Radhakrishnan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 51; nb. 49; (2012); p. 12343 - 12347; Angew. Chem.; vol. 124; nb. 49; (2012); p. 12509 - 12513,4 View in Reaxys With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide, Reflux Suess, Alison M.; Ertem, Mehmed Z.; Cramer, Christopher J.; Stahl, Shannon S.; Journal of the American Chemical Society; vol. 135; nb. 26; (2013); p. 9797 - 9804

36/118

2016-07-02 05:35:12

View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 4h, T= 20 °C , Inert atmosphere Senthilkumar, Natarajan; Parthasarathy, Kanniyappan; Gandeepan, Parthasarathy; Cheng, Chien-Hong; Chemistry - An Asian Journal; vol. 8; nb. 9; (2013); p. 2175 - 2181 View in Reaxys With thionyl chloride, Time= 2h, Reflux Li, Xin; Liu, Yan-Hua; Gu, Wen-Jia; Li, Bo; Chen, Fa-Jie; Shi, Bing-Feng; Organic Letters; vol. 16; nb. 15; (2014); p. 3904 - 3907 View in Reaxys With thionyl chloride, Time= 2h, Reflux Liu, Yue-Jin; Liu, Yan-Hua; Yin, Xue-Song; Gu, Wen-Jia; Shi, Bing-Feng; Chemistry--A European Journal; vol. 21; nb. 1; (2015); p. 205 - 209 View in Reaxys With oxalyl dichloride, N,N-dimethyl-formamide in dichloromethane, Time= 5h, T= 0 - 20 °C , Inert atmosphere, Schlenk technique Prakash, Sekar; Muralirajan, Krishnamoorthy; Cheng, Chien-Hong; Chemical Communications; vol. 51; nb. 69; (2015); p. 13362 - 13364 View in Reaxys Cl

O O

F N O

F O

O Cl

F N O

F O

Rx-ID: 24969046 View in Reaxys 12/294 Yield

Conditions & References 1.A : (A) (A) 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoyl chloride. A solution of 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid (448.1 g, 1.24 mole), thionyl chloride (458 g) and toluene (250 ml) was held at reflux for 8 hrs. The excess thionyl chloride and the solvent were stripped off under reduced pressure to give a reddish solid, which upon recrystallization from hexane-toluene afforded 282.9 g of the desired benzoyl chloride as a light yellow crystalline solid; mp 63°-69° C. With thionyl chloride in toluene Patent; GAF Corporation; US4568382; (1986); (A1) English View in Reaxys 1.A : (A) (A) 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitro benzoyl chloride A solution of 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoic acid (448.1 g, 1.24 mole), thionyl chloride (458 g) and toluene (250 ml) was held at reflux for 8 hrs. The excess thionyl chloride and the solvent were stripped off under reduced pressure to give a reddish solid, which upon recrystallization from hexane-toluene afforded 282.9 g of the desired benzoyl chloride as a light yellow crystalline solid; mp 63°-69° C. With thionyl chloride in toluene Patent; GAF Corporation; US4435588; (1984); (A1) English View in Reaxys 1.C : Preparation of 2-(2,4-Dichlorophenoxyacetoxy)ethyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate

37/118

2016-07-02 05:35:12

(C) 5-[2-Chloro-4-trifluoromethylphenoxy]-2-nitrobenzoyl chloride. A solution of 5-[2-chloro-4-trifluoromethylphenoxy]-2-nitrobenzoic acid (448.1 g, 1.24 mole), thionyl chloride (458 g) and toluene (250 ml) was held at reflux for 8 hrs. The excess thionyl chloride and the solvent were stripped off under reduced pressure to give a reddish solid, which upon recrystallization from hexane-toluene afforded 282.9 g of the desired benzoyl chloride as a light yellow crystalline solid; m.p. 63°-69° C. With thionyl chloride in toluene Patent; GAF Corporation; US4429146; (1984); (A1) English View in Reaxys O

Rx-ID: 36713312 View in Reaxys 13/294 Yield

Conditions & References

71 %

With Pd0(tris(tert-butyl)phosphine)2, (benzyl)-triphenylphosphonium chloride in toluene, Time= 24h, T= 110 °C , p= 38002.6Torr , Glovebox, Autoclave, Inert atmosphere Quesnel, Jeffrey S.; Arndtsen, Bruce A.; Journal of the American Chemical Society; vol. 135; nb. 45; (2013); p. 16841 - 16844 View in Reaxys

Rx-ID: 31758150 View in Reaxys 14/294 Yield

Conditions & References 1 : Benzoyl Chloride Benzoyl Chloride Benzoic acid (610 mg, 5 mmol) is dissolved in freshly distilled dichloromethane (10 mL) under nitrogen. Oxalyl chloride (635 μL, 7.5 mmol) is then added dropwise, followed by dimethylformamide (40 μL, 0.5 mmol). The reaction is stirred at room temperature for 20 hours. The medium is then concentrated on a rotary evaporator and then used directly in the reaction with propargylamine. With benzoic acid in N-methyl-acetamide, dichloromethane, monopropargylamine Patent; POLYINTELL; US2011/263446; (2011); (A1) English View in Reaxys Benzoyl Chloride Benzoyl Chloride Benzoic acid (610 mg, 5 mmol) is dissolved in freshly distilled dichloromethane (10 mL) under nitrogen. Oxalyl chloride (635 μL, 7.5 mmol) is then added dropwise, followed by dimethylformamide (40 μL, 0.5 mmol). The reaction is stirred at room temperature for 20 hours. The medium is then concentrated on a rotary evaporator and then used directly in the reaction with propargylamine. With benzoic acid in N-methyl-acetamide, dichloromethane, monopropargylamine Patent; POLYINTELL; US2011/263446; (2011); (A1) English View in Reaxys O N

O O

Cl F

Rx-ID: 25457486 View in Reaxys 15/294 Yield

Conditions & References B : Preparation of 2-Nitro-4-Trifluoromethylbenzoic Acid

38/118

2016-07-02 05:35:12

A solution of 9.8 g of 2-nitro-4-trifluoromethylbenzoic acid and 20 ml thionyl chloride in chloroform/THF was heated to reflux for 7 hours. The volatiles were removed under reduced pressure. The residue was diluted with ether and the solvent removed under reduced pressure to yield 10.2 g of the desired benzoyl chloride, IR (neat) 1795 cm-1 (C=O). With thionyl chloride in tetrahydrofuran, chloroform Patent; Rohm and Haas Company; US4781750; (1988); (A1) English View in Reaxys 18

18O

Rx-ID: 42394981 View in Reaxys 16/294 Yield

Conditions & References Preparation of Benzoyl-O18-chloride To a 50 mL round bottom flask was added benzoic acid-O18 (0.200 g; 1.6 mmol). Thionyl chloride (1 mL) was added and a reflux condenser was attached to the flask. The reaction mixture was placed into an 80 °C oil bath and heated for 1 h. The reaction mixture was cooled to room temperature and the volatiles were removed by vacuum via rotary evaporation, leaving a light yellow oil. 1H NMR spectroscopic analysis revealed a single molecule and the NMR spectrum matched that previously reported [33]. With thionyl chloride, Time= 1h, T= 80 °C Zu, Chengli; Mukhopadhyay, Sukrit; Hanley, Patrick S.; Xia, Shijing; Bell, Bruce M.; Grigg, David; Gilbert, Jeffrey R.; OBrien, John P.; Journal of the American Society for Mass Spectrometry; vol. 27; nb. 5; (2016); p. 917 926 View in Reaxys

Cl N

Rx-ID: 5168343 View in Reaxys 17/294 Yield

Conditions & References With hydrogenchloride in tetrahydrofuran, Time= 30h, T= 50 °C , Yield given, Yields of byproduct given Cox, Christopher; Wack, Harald; Lectka, Thomas; Angewandte Chemie - International Edition; vol. 38; nb. 6; (1999); p. 798 - 800 View in Reaxys

O Cl

O O

Cl Cl

Rx-ID: 24273774 View in Reaxys 18/294 Yield

Conditions & References 4 : Preparation of 5-bromo-6-chloro-6'-methyl-2,2'3',4'-tetramethoxy-benzophenone EXAMPLE 4 Preparation of 5-bromo-6-chloro-6'-methyl-2,2'3',4'-tetramethoxy-benzophenone 4A Ethyl 5-bromo-6-chloro-2-methoxybenzoate A mixture of ethyl 6-chloro-2-methoxybenzoate (1.8 g, 8.4 mmol), bromine (1.41 g, 8.8 mmol) and acetic acid (5 ml) is stirred at room temperature for 24 hours. The reaction mixture is poured into water and extracted with ethyl acetate.

39/118

2016-07-02 05:35:12

The organic phase is separated and concentrated and the residue is purified by column chromatography (petrol ether: ethyl acetate, 95:5 v/v) yielding the pure product as a yellow oil, 1.7 g, (69.percent). 4B 5-Bromo-6-chloro-2-methoxybenzoic acid A mixture of 4A (1.7 g, 5.8 mmol), water (10 ml), ethanol (20 ml) and sodium hydroxide (0.5 g, 12.5 mmol) is heated under reflux with stirring. The reaction mixture is diluted with water (80 ml) and acidified with concentrated hydrochloric acid. The solid material is collected by filtration, washed with water and dried yielding white crystals, 1.3 g (85percent), mp 186-188° C. 4C 5-Bromo-6-chloro-2-methoxybenzoyl chloride A mixture of 4B (1.2 g, 4.6 mmol), dichloromethane (15 ml) and oxalyl chloride (1 ml) is stirred at room temperature for 2 hours. The mixture is concentrated and the resulting benzoylchloride is used without further purification. 4D 5-bromo-6-chloro-6'-methyl-2,2'3',4'-tetramethoxy-benzophenone With sodium hydroxide, bromine, acetic acid in ethanol, dichloromethane, water Patent; American Cyanamid Company; US5922905; (1999); (A1) English View in Reaxys O

OH Na + O–

Rx-ID: 24349105 View in Reaxys 19/294 Yield

Conditions & References 11 : (R)-4-Cyano-N-[7-(dipropylamino)-5,6,7,8-tetrahydro-2-naphthalenyl]benzenesulfonamide. 21 Thionyl chloride (3.3 ml) was added slowly to this benzylic alcohol (13.6 g) in THF at 0° and then the ice bath was removed. After an hour, aqueous sodium bicarbonate was added and it was extracted with ether. The ether layer was washed with water and brine and was dried with sodium sulfate. Solvent was removed under vacuum and the residue was chromatographed on silica gel with dichloromethane/ hexane to give 9.6 g of the benzylic chloride as a solid, m.p. 90-93° C. [α]D =+50° (25° C., CH3 OH, c=0.94). With thionyl chloride in tetrahydrofuran Patent; Pharmacia and Upjohn Company; US6084130; (2000); (A1) English View in Reaxys

S HO

S Cl

Rx-ID: 24583747 View in Reaxys 20/294 Yield

Conditions & References b : EXAMPLE 12 STR24 (a.) 5-Carboethoxythiophen-2-carboxylic acid (35): (b.) 5-Carboethoxythiophen-2-carbonyl chloride (36): To a suspension of acid 35 (0.64 g, 3.2 mmol) in dichloromethane (20 mL) under argon at room temperature was added a 2.0M solution of (COCl)2 in dichloromethane (2.4 mL, 4.8 mmol) and two drops of DMF, and stirred overnight. Excess (COCl)2 and dichloromethane were removed at reduced pressure, and the viscous, light, yellow product was dried overnight to afford the desired benzoyl chloride 36 as a yellow solid. The structure of the product was also confirmed using IR and 1 H NMR spectroscopy. With (COCl)2 in dichloromethane, N,N-dimethyl-formamide Patent; SRI International; La Jolla Cancer Research Foundation; US5466861; (1995); (A1) English View in Reaxys

O Cl

Cl Cl

Rx-ID: 24650183 View in Reaxys 21/294

40/118

2016-07-02 05:35:12

Yield

Conditions & References 4 : Preparation of Benzoyl Chloride EXAMPLE 4 Preparation of Benzoyl Chloride α, α,α-Trichlorotoluene (19.6 g; 0.1M), ferric chloride (4.1 g; 0.02M) and 1,2-dichloroethane (500 ml) were stirred under reflux under heavier than water Dean and Stark apparatus. Water (1.8 g) was then added to the Dean and Stark apparatus and the mixture was refluxed for 4 hours. By this time, all of the water had been consumed. The mixture was then filtered through Hyflo (Trade Mark) to remove the ferric chloride. With iron(III) chloride in water Patent; American Cyanamid Co.; US5639888; (1997); (A1) English View in Reaxys

O C

N O

Cl Cl

Rx-ID: 25117637 View in Reaxys 22/294 Yield

Conditions & References 1 : EXAMPLE 1 EXAMPLE 1 44 g (0.55 mole) of gaseous sulfur trioxide diluted with nitrogen are introduced at 0° to 6° C. into a solution of 66.5 g (0.5 mole) of p-tolyl isocyanate in 300 ml of 1,2-dichloroethane. The reaction product is then filtered off under suction from the dichloroethane, washed with dichloroethane and dried in an exsiccator. According to IR- and nuclear resonance spectra, the product obtained is the uretdione of p-tolyl isocyanato-o-sulfonic acid. 20 g of the sulfonation product are heated under nitrogen in 130 ml of benzotrichloride, hydrogen chloride being given off at temperatures above 100° C. The solution becomes clear at 110° C. The reaction mixture is then further heated until, at 140° C., the elimination of hydrogen chloride ceases. After the mixture of excess benzotrichloride and benzoyl chloride formed during the reaction has been distilled off, the residue is distilled at 118° C. to 123° C./0.1 Torr. 16.1 g of 1-isocyanato-2-chlorosulfonyl-4-methyl benzene are obtained. M.p.: 36° to 38.5° C. With sulfur trioxide in α,α,α-trichlorotoluene, 1,2-dichloro-ethane Patent; Bayer Aktiengesellschaft; US4359426; (1982); (A1) English View in Reaxys O

Cl O

N O

Cl HO

Rx-ID: 25467672 View in Reaxys 23/294 Yield

Conditions & References C : Preparation of 2-Nitro-p-Toluic Acid EXAMPLE C Preparation of 2-Nitro-p-Toluic Acid A slurry of 100 g of 4-chloro-3-nitrotoluene and 80 g of copper (I) cyanide in 500 ml of DMF was refluxed for 12 hours. An additional 20 g of CuCN was added and the reaction refluxed another 4 hours. Ether was added and the ether phase decanted from the dark oil. The ether phase was dried with molecular sieves, filtered and the solvent removed under reduced pressure to yield an orange-brown semi-solid. The semi-solid product was triturated with hexane.

41/118

2016-07-02 05:35:12

The hexane was evaporated off under reduced pressure to yield 30.5 g of the desired product which was used without further purification. The benzonitrile (10 g) was refluxed for 90 min. in 50percent aq H2 SO4. TLC indicated complete hydrolysis of the nitrile. The reaction was pured onto ice and extracted with ether. The ether phase was washed with saturated brine, dried over molecular sieves, filtered and the solvent removed under reduced pressure to yield 4.2 g of the desired product, IR (Nujol) 1695 (C=O--acid), NMR (CDCl3 /DMSO/TMS) 2.52 ppm, (S, 3H), 7.80 ppm, (M, 3H). This material was used without further purification in the preparation of the corresponding benzoyl chloride. IR (neat) 1775 cm-1 (C=O) acid halide. With CuCN in aq H2 SO4, benzonitrile, N,N-dimethyl-formamide Patent; Rohm and Haas Company; US4781750; (1988); (A1) English View in Reaxys 2H

H 2H

Rx-ID: 31325584 View in Reaxys 24/294 Yield

Conditions & References Reaction Steps: 2 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C 1.2: -78 - 20 °C 1.3: 20 °C 2.1: thionyl chloride / N,N-dimethyl-formamide / 1 h / 80 °C / Inert atmosphere With n-butyllithium, thionyl chloride in tetrahydrofuran, hexane, N,N-dimethyl-formamide Ackermann, Lutz; Lygin, Alexander V.; Hofmann, Nora; Angewandte Chemie - International Edition; vol. 50; nb. 28; (2011); p. 6379 - 6382 View in Reaxys Reaction Steps: 2 1: n-butyllithium / tetrahydrofuran / -78 °C / |Schlenk technique 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0 - 20 °C / |Inert atmosphere; |Schlenk technique With n-butyllithium, oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran, dichloromethane Karthikeyan, Jaganathan; Haridharan, Radhakrishnan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 51; nb. 49; (2012); p. 12343 - 12347; Angew. Chem.; vol. 124; nb. 49; (2012); p. 12509 - 12513,4 View in Reaxys Reaction Steps: 2 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / |Inert atmosphere 1.2: 0.17 h / -78 °C / |Inert atmosphere 2.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 20 °C / |Inert atmosphere With n-butyllithium, oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran, hexane, dichloromethane Senthilkumar, Natarajan; Parthasarathy, Kanniyappan; Gandeepan, Parthasarathy; Cheng, Chien-Hong; Chemistry - An Asian Journal; vol. 8; nb. 9; (2013); p. 2175 - 2181 View in Reaxys Reaction Steps: 2 1.1: n-butyllithium / tetrahydrofuran / -78 °C 1.2: -78 °C 2.1: thionyl chloride / dichloromethane; N,N-dimethyl-formamide / 2 h / |Reflux With n-butyllithium, thionyl chloride in tetrahydrofuran, dichloromethane, N,N-dimethyl-formamide Li, Xin; Liu, Yan-Hua; Gu, Wen-Jia; Li, Bo; Chen, Fa-Jie; Shi, Bing-Feng; Organic Letters; vol. 16; nb. 15; (2014); p. 3904 - 3907 View in Reaxys

42/118

2016-07-02 05:35:12

Reaction Steps: 2 1: n-butyllithium / tetrahydrofuran; hexane / 1.5 h / -78 °C / |Inert atmosphere; |Schlenk technique 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 5 h / 0 - 20 °C / |Inert atmosphere; |Schlenk technique With n-butyllithium, oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran, hexane, dichloromethane Prakash, Sekar; Muralirajan, Krishnamoorthy; Cheng, Chien-Hong; Chemical Communications; vol. 51; nb. 69; (2015); p. 13362 - 13364 View in Reaxys F

O HN

NH 2 S

Rx-ID: 24059380 View in Reaxys 25/294 Yield

Conditions & References

82%

6 : N-(4.6-Difluoro-benzothiazol-2-yl)-benzamide EXAMPLE 6 N-(4.6-Difluoro-benzothiazol-2-yl)-benzamide Using 2-amino-4,6-difluoro-benzothiazole and benzoyl chloride the title compound was prepared as a beige solid (82percent yield), MS: m/e=290 (M+). Patent; Alanine, Alexander; Flohr, Alexander; Miller, Aubry Kern; Norcross, Roger David; Riemer, Claus; US2002/45615; (2002); (A1) English View in Reaxys

O– O

2 Na +

NH 2

O O

3-(2', 3'-dibromopropionamido)benzoyl chloride

O–

Cl Br

Rx-ID: 24879896 View in Reaxys 26/294 Yield

Conditions & References 17 : EXAMPLE 17 EXAMPLE 17 1.7 parts of the dye of the formula (104) in Example 3 are dissolved in 50 parts of water at pH 7 by adding hydrochloric acid, and a little disodium hydrogenphosphate is added. To this solution is added 1 part of 3-(2', 3'-dibromopropionamido)benzoyl chloride (prepared by reacting 3-aminobenzoic acid with 2,3-dibromopropionyl chloride and subsequent conversion to the corresponding benzoyl chloride with thionyl chloride in the presence of dimethylformamide) dissolved in acetone, added dropwise in the course of 5 minutes. With hydrogenchloride in water Patent; Ciba-Geigy Corporation; US4994562; (1991); (A1) English View in Reaxys F

dimethylsulfoxide (DMSO)

Br F

O O F

Br F

OH O

O Cl

Rx-ID: 24892803 View in Reaxys 27/294 Yield

Conditions & References 18 : Preparation of Methyl 4-(2-Bromotetrafluoroethoxy)Benzoate, its Conversion to to 4-Trifluoroethenyloxybenzoic Acid and the Benzoyl Chloride, and Use of the Chloride to Chain Extend Polycarbonate Oligomers. EXAMPLE 18 Preparation of Methyl 4-(2-Bromotetrafluoroethoxy)Benzoate, its Conversion to to 4-Trifluoroethenyloxybenzoic Acid and the Benzoyl Chloride, and Use of the Chloride to Chain Extend Polycarbonate Oligomers.

43/118

2016-07-02 05:35:12

Methyl 4-hydroxybenzoate (304.3 g, 2 mol) is dissolved in 800 mL of methanol and is converted to the potassium salt by the slow addition of potassium hydroxide (132.02 g, 2 mol, 85percent purity). The resulting mixture is stirred and cooled as necessary to maintain the temperature below 50° C. The solvent is then removed by rotary evaporation and the crystalline salt is dried under vacuum overnight at 140° C. The dried salt is allowed to cool and transferred to an oven dried 2L flask under nitrogen. The flask is fitted with a mechanical stirrer, thermometer, heating mantle, condenser and pressure-equalizing addition funnel. Dry dimethylsulfoxide (DMSO) (550 g) is added and the mixture is stirred and warmed to 60° C. as 1,2-dibromotetrafluoroethane (537 g, 2.06 mol) is added slowly. (No appreciable reaction is observed at lower temperatures.) Reaction temperature is maintained at 65°-70° C. for two hours after addition is complete. The mixture is then heated to 90° C. and allowed to cool overnight. Product is isolated by extracting the mixture with 500 mL of water to remove salts and DMSO. The product separates as an orange oil which is washed with water to remove residual DMSO. (The upper aqueous layer is extracted with methylene chloride, and the methylene chloride solution is evaporated to yield about 40 g of product which is added to the rest of the product prior to the water washes.) The product (623 g) is distilled at 85° C./0.3 mm Hg to yield 561 g of colorless oil, 85percent yield. The product is identified by 19F NMR, 1H NMR, and IR spectra. With potassium hydroxide in methanol Patent; The Dow Chemical Company; US5023380; (1991); (A1) English View in Reaxys Cl

H 2N

Cl 2 H N

NH Cl

N N

Rx-ID: 24963896 View in Reaxys 28/294 Yield

Conditions & References 1 : 3-Chloro-N-[3-(1H-imidazol-1-yl)propyl]benzamide EXAMPLE 1 3-Chloro-N-[3-(1H-imidazol-1-yl)propyl]benzamide A mixture of 6.0 g. of 1H-imidazole-1-propanamine dihydrochloride, 45 ml. of 2N sodium hydroxide and 150 ml. of methylene chloride was stirred at room temperature and 3.9 ml. of 3-chlorobenzoyl chloride was added. The reaction mixture was stirred for 18 hours, then methylene chloride and 15 ml. of 1N sodium hydroxide were added and the layers were separated. The organic layer was washed with water, dried over magnesium sulfate, and concentrated to remove the solvent. The residue was triturated with diethyl ether and the crystalline product recovered by filtration and recrystallized from ethanol, giving the desired product, m.p. 125°-127° C. Following the procedure of this example and using the appropriate benzoyl chloride, the products of Examples 2-19 were obtained as set forth in Table III below. With sodium hydroxide in dichloromethane Patent; American Cyanamid Company; US4568687; (1986); (A1) English View in Reaxys

O O

N S

N N H

H 2N

Rx-ID: 24070370 View in Reaxys 29/294

44/118

2016-07-02 05:35:12

Yield

Conditions & References

72%

30 : N-(4-Methoxy-7-phenoxy-benzothiazol-2-yl)-benzamide EXAMPLE 30 N-(4-Methoxy-7-phenoxy-benzothiazol-2-yl)-benzamide Using 4-Methoxy-7-phenoxy-benzothiazol-2-ylamine and benzoyl chloride the title compound was obtained crude, which was chromatographed over SiO2 (Merck 230-400 mesh) eluding with CH2Cl2/EtOAc (1:1), to afford the pure title compound as a white solid (72percent yield), MS: m/e=376.1 (M+). Patent; Alanine, Alexander; Flohr, Alexander; Miller, Aubry Kern; Norcross, Roger David; Riemer, Claus; US2002/45615; (2002); (A1) English View in Reaxys

O HO

O O

Rx-ID: 24343928 View in Reaxys 30/294 Yield

Conditions & References 1.A : 2-(2,3-Dimethoxy-phenyl)-4,4-dimethyl-4-oxazoline EXAMPLE 1A 2-(2,3-Dimethoxy-phenyl)-4,4-dimethyl-4-oxazoline At room temperature, add dropwise thionyl chloride (66 mL, 107.6 g, 0.9 mole) to 2,3-dimethoxy benzoic acid (54.63 g., 0.3 mole) and stir overnight until formation of the benzoyl chloride is complete. Remove excess thionyl chloride and any gas evolved on a rotary evaporator. Add additional toluene to remove any residual thionyl chloride from the reaction vessel. With thionyl chloride Patent; Hoechst Marion Roussel, Inc.; US6004959; (1999); (A1) English View in Reaxys 1.A : 2-(2,3-Dimethoxy-phenyl)-4,4-dimethyl-4-oxazoline Example 1A 2-(2,3-Dimethoxy-phenyl)-4,4-dimethyl-4-oxazoline At room temperature, add dropwise thionyl chloride (66 mL, 107.6 g, 0.9 mole) to 2,3-dimethoxy benzoic acid (54.63 g., 0.3 mole) and stir overnight until formation of the benzoyl chloride is complete. Remove excess thionyl chloride and any gas evolved on a rotary evaporator. Add additional toluene to remove any residual thionyl chloride from the reaction vessel. With thionyl chloride Patent; Aventis Pharmaceuticals Inc.; EP906268; (2001); (B1) English View in Reaxys O

Cl I

Rx-ID: 34588535 View in Reaxys 31/294 Yield

Conditions & References Reaction Steps: 3 1.1: isopropylmagnesium chloride / tetrahydrofuran; diethyl ether / 2 h / -78 °C / |Inert atmosphere; |Schlenk technique 1.2: 0.5 h / 20 °C / |Inert atmosphere; |Schlenk technique 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / 78 °C / |Inert atmosphere; |Schlenk technique 2.2: 0.17 h / -78 - 20 °C 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 0 - 20 °C / |Inert atmosphere; |Schlenk technique With n-butyllithium, oxalyl dichloride, isopropylmagnesium chloride, N,N-dimethyl-formamide in tetrahydrofuran, diethyl ether, hexane, dichloromethane

45/118

2016-07-02 05:35:12

Karthikeyan, Jaganathan; Haridharan, Radhakrishnan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 51; nb. 49; (2012); p. 12343 - 12347; Angew. Chem.; vol. 124; nb. 49; (2012); p. 12509 - 12513,4 View in Reaxys Reaction Steps: 3 1.1: isopropylmagnesium chloride / tetrahydrofuran; diethyl ether / 2 h / -78 °C / |Inert atmosphere 1.2: 0.5 h / -78 - 20 °C / |Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / |Inert atmosphere 2.2: 0.17 h / -78 °C / |Inert atmosphere 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 20 °C / |Inert atmosphere With n-butyllithium, oxalyl dichloride, isopropylmagnesium chloride, N,N-dimethyl-formamide in tetrahydrofuran, diethyl ether, hexane, dichloromethane Senthilkumar, Natarajan; Parthasarathy, Kanniyappan; Gandeepan, Parthasarathy; Cheng, Chien-Hong; Chemistry - An Asian Journal; vol. 8; nb. 9; (2013); p. 2175 - 2181 View in Reaxys Reaction Steps: 3 1.1: isopropylmagnesium chloride / tetrahydrofuran; diethyl ether / 2 h / -78 °C 1.2: 0.5 h / -78 - 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C 2.2: 0.33 h / -78 °C 3.1: thionyl chloride / 2 h / |Reflux With n-butyllithium, thionyl chloride, isopropylmagnesium chloride in tetrahydrofuran, diethyl ether Li, Xin; Liu, Yan-Hua; Gu, Wen-Jia; Li, Bo; Chen, Fa-Jie; Shi, Bing-Feng; Organic Letters; vol. 16; nb. 15; (2014); p. 3904 - 3907 View in Reaxys Reaction Steps: 3 1: isopropylmagnesium chloride / tetrahydrofuran; diethyl ether / 2 h / -78 °C / |Inert atmosphere; |Schlenk technique 2: n-butyllithium / tetrahydrofuran; hexane / 1.5 h / -78 °C / |Inert atmosphere; |Schlenk technique 3: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 5 h / 0 - 20 °C / |Inert atmosphere; |Schlenk technique With n-butyllithium, oxalyl dichloride, isopropylmagnesium chloride, N,N-dimethyl-formamide in tetrahydrofuran, diethyl ether, hexane, dichloromethane Prakash, Sekar; Muralirajan, Krishnamoorthy; Cheng, Chien-Hong; Chemical Communications; vol. 51; nb. 69; (2015); p. 13362 - 13364 View in Reaxys O 2H

Cl Br

Rx-ID: 34588538 View in Reaxys 32/294 Yield

Conditions & References Reaction Steps: 2 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / 78 °C / |Inert atmosphere; |Schlenk technique 1.2: 0.17 h / -78 - 20 °C 2.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 0 - 20 °C / |Inert atmosphere; |Schlenk technique With n-butyllithium, oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran, hexane, dichloromethane Karthikeyan, Jaganathan; Haridharan, Radhakrishnan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 51; nb. 49; (2012); p. 12343 - 12347; Angew. Chem.; vol. 124; nb. 49; (2012); p. 12509 - 12513,4 View in Reaxys Reaction Steps: 2 1.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / -78 °C / |Inert atmosphere 1.2: 0.17 h / -78 °C / |Inert atmosphere 2.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 20 °C / |Inert atmosphere With n-butyllithium, oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran, hexane, dichloromethane

46/118

2016-07-02 05:35:12

Senthilkumar, Natarajan; Parthasarathy, Kanniyappan; Gandeepan, Parthasarathy; Cheng, Chien-Hong; Chemistry - An Asian Journal; vol. 8; nb. 9; (2013); p. 2175 - 2181 View in Reaxys Reaction Steps: 2 1.1: n-butyllithium / tetrahydrofuran / 0.67 h / -78 °C 1.2: 0.33 h / -78 °C 2.1: thionyl chloride / 2 h / |Reflux With n-butyllithium, thionyl chloride in tetrahydrofuran Li, Xin; Liu, Yan-Hua; Gu, Wen-Jia; Li, Bo; Chen, Fa-Jie; Shi, Bing-Feng; Organic Letters; vol. 16; nb. 15; (2014); p. 3904 - 3907 View in Reaxys Reaction Steps: 2 1: n-butyllithium / tetrahydrofuran; hexane / 1.5 h / -78 °C / |Inert atmosphere; |Schlenk technique 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 5 h / 0 - 20 °C / |Inert atmosphere; |Schlenk technique With n-butyllithium, oxalyl dichloride, N,N-dimethyl-formamide in tetrahydrofuran, hexane, dichloromethane Prakash, Sekar; Muralirajan, Krishnamoorthy; Cheng, Chien-Hong; Chemical Communications; vol. 51; nb. 69; (2015); p. 13362 - 13364 View in Reaxys O O

S Cl Cl

S Cl

Rx-ID: 41196925 View in Reaxys 33/294 Yield 83 %

Conditions & References Stage 1: With pyridine, thionyl chloride, Time= 6.5h, T= 75 °C Stage 2: in neat (no solvent), Time= 15h, T= 140 °C Zaragoza, Florencio; Journal of Organic Chemistry; vol. 80; nb. 20; (2015); p. 10370 - 10374 View in Reaxys H 2N Cl

O O

Cl Br

NH 2

Rx-ID: 42374048 View in Reaxys 34/294 Yield

Conditions & References 15 : Synthesis of Compounds Via Scheme 15 EXAMPLE 15 Synthesis of Compounds Via Scheme 15 The following compounds were prepared according to Scheme 15. To an ice-cooled solution of 2-methoxy-6-methylaniline (S15-1, 25.12 g, 183.10 mmol, 1 equiv) in MeOH (79 mL) and HOAc (25 mL) was added a solution of bromine (9.41 mL, 183.10 mmol) in HOAc (79 mL) dropwise via an addition funnel. The reaction mixture was allowed to warm to rt and stirred for 2 hrs after complete addition. EtOAc (150 mL) was added, and the solid was collected by filtration and washed with more EtOAc, yielding 37.20 g of compound S15-2 as an off-white solid (HBr salt). 4-Bromo-2-methoxy-6-methylaniline (S15-2, HBr salt, 20.00 g, 92.70 mmol, 1.0 equiv) was suspended in concentrated HCl (22 mL) and crushed ice (76 g) cooled in an ice-bath. A solution of NaNO2 (6.52 g, 94.60 mmol, 1.02 equiv) in H2O (22 mL) was added dropwise. The resulting mixture was stirred at 0° C. for 30 min and neutralized with aqueous Na2CO3. A suspension of CuCN (10.4 g, 115.90 mmol, 1.25 equiv) in H2O (44 mL) was mixed with a solution of NaCN (14.4 g, 294.80 mmol, 3.18 equiv) in 22 mL of H2O, and cooled in an ice-bath. The initial diazonium salt mixture was then added to the CuCN and NaCN mixture with vigorous stirring while maintaining the temperature at 0° C. (toluene (180 mL) was also added in portions during the addition).

47/118

2016-07-02 05:35:12

The reaction mixture was stirred at 0° C. for 1 h, rt for 2 hrs, and 50° C. for another 1 h. After cooling to rt, the layers were separated. The aqueous layer was extracted with toluene. The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated. The residue was passed through a silica gel plug, washed with toluene, and concentrated to yield 14.50 g of compound S15-3 as a light yellow solid. To a solution of S15-3 (11.34 g, 50.20 mmol, 1.0 equiv) in THF (100 mL) was added 1.5 M DIBAL-H in toluene (40.10 mL, 60.20 mmol, 1.2 equiv) slowly at -78° C. The reaction was allowed to warm to rt gradually and stirred overnight. After re-cooled to 0° C., the reaction was carefully quenched by 1 N HCl. The resulting mixture was stirred at rt for 1 h and extracted three times with EtOAc. The combined EtOAc layers were washed with H2O, saturated aqueous NaHCO3 and brine, dried over magnesium sulfate, and concentrated to provide compound S15-4 as a yellow solid, which was used directly in the next step. To a suspension of S15-4 (50.20 mmol, 1.0 equiv) in t-BuOH (200 mL) was added a solution of NaClO2 (11.34 g, 100.30 mmol, 2.0 equiv) and NaH2PO4 (34.6 g, 250.80 mmol, 5.0 equiv) in H2O (100 mL) via an addition funnel. After complete addition, 2-methyl-2-butene (42.40 mL, 0.40 mol, 8 equiv)) was added. The resulting homogenous solution was stirred at rt for 30 min, and volatiles were removed. The residue was suspended in 150 mL of H2O. The solution was acidified to pH ˜1 with 1 N HCl and extracted three times with t-butyl methyl ether. The combined organic solution was extracted three times with 1 N NaOH. The combined aqueous solution was acidified with 6 N HCl, and extracted three times with EtOAc. The combined EtOAc extracts were washed with brine, dried over magnesium sulfate, and concentrated to provide 8.64 g of the benzoic acid intermediate (15-4-a) as an off-white solid, which was used directly in the next step. To a solution of the above benzoic acid (8.64 g, 35.20 mmol, 1.0 equiv) in dichloromethane (70 mL) was added oxalyl chloride (3.76 mL, 42.30 mmol, 1.2 equiv), followed by a couple of drops of DMF (caution: gas evolution). The mixture was stirred at rt for 30 min and the volatiles were evaporated under reduce pressure. The residue was further dried under high vacuum to afford the crude benzoyl chloride. The crude benzoyl chloride was re-dissolved in dichloromethane (70 mL). With sodium chlorite, sodium dihydrogenphosphate, benzoic acid, sodium nitrite in tetrahydrofuran, hydrogenchloride, dichloromethane, water, ethyl acetate, toluene, tert-butyl alcohol, liquid HCl Patent; TETRAPHASE PHARMACEUTICALS, INC.; Chen, Chi-Li; Clark, Roger B.; Deng, Yonghong; He, Minsheng; Plamondon, Louis; Sun, Cuixiang; Xiao, Xiao-Yi; Rönn, Magnus; (444 pag.); US9315451; (2016); (B2) English View in Reaxys

O Cl

O–

O O+

Cl OO

O Cl

Rx-ID: 2656340 View in Reaxys 35/294 Yield 80 %

Conditions & References With hydrogenchloride in toluene Schroth,Werner; Spitzner, Roland; Tetrahedron Letters; vol. 26; nb. 33; (1985); p. 3963 - 3966 View in Reaxys

Rx-ID: 4360113 View in Reaxys 36/294 Yield

Conditions & References With tetraphthaloyl chloride in tetrahydrofuran, Time= 0.0833333h, T= 80 °C Mathews; Burns; Dannals; Ravert; Naylor; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 36; nb. 8; (1995); p. 729 - 737 View in Reaxys

48/118

2016-07-02 05:35:12

With hydrogenchloride, thionyl chloride in tetrahydrofuran, diethyl ether, Time= 0.05h, T= 65 °C Van Tilburg; Franssen; Van Der Hoeven; Van Der Meij; Elshove; Lammertsma; Windhorst; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 47; nb. 11; (2004); p. 763 - 777 View in Reaxys With thionyl chloride, N,N-dimethyl-formamide, Time= 0.0333333h, T= 100 °C Riss, Patrick J.; Lu, Shuiyu; Telu, Sanjay; Aigbirhio, Franklin I.; Pike, Victor W.; Angewandte Chemie - International Edition; vol. 51; nb. 11; (2012); p. 2698 - 2702 View in Reaxys

S N

Rx-ID: 24362280 View in Reaxys 37/294 Yield

Conditions & References 39.B : Part B. To the crude benzoyl chloride obtained and suspended in anhydrous chlorobenzene (10 mL) was added 2-dimethylamino-6-methoxybenzo[b]thiophene (1.02 g, 4.92 mmol. in chlorobenzene Patent; Eli Lilly and Company; US6025382; (2000); (A1) English View in Reaxys

Rx-ID: 601767 View in Reaxys 38/294 Yield

Conditions & References With iron(III) chloride, benzotrichloride in benzene, T= 60 °C , ΔH(activ.), ΔS(activ.), various temperature, various solvents, various concentration ratios, Rate constant, Mechanism, Thermodynamic data Dvorko, G. F.; Litvinenko, G. S.; J. Gen. Chem. USSR (Engl. Transl.); vol. 55; nb. 8; (1985); p. 1828 - 1835,1624 1630 View in Reaxys With chlorine Gautier; Annales de Chimie (Cachan, France); vol. <6> 14; (1888); p. 362 View in Reaxys Woehler; Liebig; Justus Liebigs Annalen der Chemie; vol. 3; (1832); p. 262 View in Reaxys With disulfur dichloride, T= 150 °C , im geschlossenen Rohr Loth; Michaelis; Chemische Berichte; vol. 27; (1894); p. 2548 View in Reaxys With sulfuryl dichloride Durrans; Journal of the Chemical Society; vol. 121; (1922); p. 46 View in Reaxys With chlorine, T= 22.85 °C , p= 700Torr , UV-irradiation, Chlorination, Product distribution, Kinetics Caralp, Francoise; Foucher, Virginie; Lesclaux, Robert; Wallington, Timothy J.; Hurley, Michael D.; Physical Chemistry Chemical Physics; vol. 1; nb. 15; (1999); p. 3509 - 3517 View in Reaxys With oxygen, chlorine, T= 22.85 °C , p= 700Torr , UV-irradiation, Chlorination, Product distribution, Kinetics

49/118

2016-07-02 05:35:12

Caralp, Francoise; Foucher, Virginie; Lesclaux, Robert; Wallington, Timothy J.; Hurley, Michael D.; Physical Chemistry Chemical Physics; vol. 1; nb. 15; (1999); p. 3509 - 3517 View in Reaxys Reaction Steps: 2 1.1: sodium dihydrogenphosphate; dihydrogen peroxide; sodium chlorite / water; acetonitrile / 1.5 h / 10 - 20 °C 1.2: 0.08 h 2.1: thionyl chloride / dichloromethane; N,N-dimethyl-formamide / 1 h / 20 °C With sodium chlorite, sodium dihydrogenphosphate, thionyl chloride, dihydrogen peroxide in dichloromethane, water, N,N-dimethyl-formamide, acetonitrile Zhao, Chao; Liu, Zai-Qun; Biochimie; vol. 95; nb. 4; (2013); p. 842 - 849 View in Reaxys With trichloroisocyanuric acid in dichloromethane, Time= 120h, T= 20 °C , Inert atmosphere Gaspa, Silvia; Porcheddu, Andrea; De Luca, Lidia; Organic Letters; vol. 17; nb. 15; (2015); p. 3666 - 3669 View in Reaxys With tert.-butylhydroperoxide, N-chloro-succinimide, tris(2,2'-bipyridyl)ruthenium dichloride in acetonitrile, Time= 24h, T= 20 °C , Sealed tube, Irradiation, Solvent, Reagent/catalyst Iqbal, Naeem; Cho, Eun Jin; Journal of Organic Chemistry; vol. 81; nb. 5; (2016); p. 1905 - 1911 View in Reaxys 18O

Cl Cl

Rx-ID: 5007388 View in Reaxys 39/294 Yield

Conditions & References With water, Time= 48h, T= 110 °C Porter, Ned A.; Caldwell, Sarah E.; Lowe, Jennifer R.; Journal of Organic Chemistry; vol. 63; nb. 16; (1998); p. 5547 - 5554 View in Reaxys With water Porter; Yin; Pratt; Journal of the American Chemical Society; vol. 122; nb. 45; (2000); p. 11272 - 11273 View in Reaxys Reaction Steps: 2 1: water / 24 h / 120 °C / |Sealed tube 2: thionyl chloride / 1 h / 90 °C / |Sealed tube With thionyl chloride, water Hu, Yancheng; Yi, Ruxia; Yu, Xinzhang; Xin, Xiaoyi; Wang, Chunxiang; Wan, Boshun; Chemical Communications; vol. 51; nb. 84; (2015); p. 15398 - 15401 View in Reaxys OH

Cl O

O Cl

O O O

O Cl

Rx-ID: 24198045 View in Reaxys 40/294 Yield

Conditions & References e : Notes e) The benzoyl chloride was prepared by the dropwise addition of oxalyl chloride (0.75 mmol) to a stirred mixture of 3,4diethoxybenzoic acid (0.75 mmol) and DMF (a few drops) which had been cooled to 0° C. The mixture was allowed to warm to ambient temperature and was stirred for four hours. The resultant solution was evaporated and the resultant acid chloride was used without further purification.

50/118

2016-07-02 05:35:12

The benzamide product gave the following data: Mass M+H 453. in N,N-dimethyl-formamide Patent; Zeneca Limited; US6498274; (2002); (B1) English View in Reaxys Cl

Rx-ID: 24199749 View in Reaxys 41/294 Yield

Conditions & References 9 : Typical Identifier Preparations A solution of the acid (76 mg, 0.188 mmol) in methylene chloride (2 mL) was treated with oxalylchloride (36 mg, 0.28 mmol) and catalytic DMF. After stirring for 10 min at room temperature slow but steady evolution of gas was observed. Stirring continued for 2 hrs. when the solution was diluted with DCM (15 mL) and washed with saturated aqueous sodium hydrogencarbonate solution (5 mL). The layers were separated. The organic layer was dried (Na2SO4) and the solvent evaporated affording the benzoyl chloride as pale yellow crystals. in dichloromethane Patent; The Trustees of Columbia University in the City of New York; Cold Spring Harbor Laboratory; US6503759; (2003); (B1) English View in Reaxys

H 2N NH 3 O

N O

Rx-ID: 25459817 View in Reaxys 42/294 Yield

Conditions & References 4 : (+-)-N-[2-[[[[2,6-bis(1-methylethyl)phenyl]amino]carbonyl]amino]-1-phenylethyl]benzenecarboxamide The amine benzamide (28.7 g, 0.12 mole) was dissolved in 700 mL of THF followed by the addition of 24.3 g (0.12 mole) 2,6-diisopropylphenylisocyanate in one portion. The reaction was stirred for 4 hours. The precipitate was collected by filtration and washed with hexane. The product was dried in vacuo at 40°C for 3 hours to give the title compound, m.p. 249-250°C. Following the general procedure of Example 4, only substituting the acid chloride listed below for benzoyl chloride, the respective products listed in Table 3 were obtained. in tetrahydrofuran Patent; WARNER-LAMBERT COMPANY; EP432442; (1991); (A1) English View in Reaxys O

Rx-ID: 40278891 View in Reaxys 43/294 Yield

Conditions & References With Pd0(tris(tert-butyl)phosphine)2, (benzyl)-triphenylphosphonium chloride in toluene, Time= 24h, T= 110 °C , p= 15201Torr , Autoclave, Glovebox Quesnel, Jeffrey S.; Kayser, Laure V.; Fabrikant, Alexander; Arndtsen, Bruce A.; Chemistry - A European Journal; vol. 21; nb. 26; (2015); p. 9550 - 9555 View in Reaxys

51/118

2016-07-02 05:35:12

Cl N

O–

Z O+

Cl OO

O Cl

Rx-ID: 2536348 View in Reaxys 44/294 Yield 64 %

Conditions & References With hydrogenchloride in toluene, Heating Schroth,Werner; Spitzner, Roland; Tetrahedron Letters; vol. 26; nb. 33; (1985); p. 3963 - 3966 View in Reaxys Cl Cl

2 HCl

H 2N N

O Cl

N N

Rx-ID: 24968289 View in Reaxys 45/294 Yield

Conditions & References 64 : 3,4-Dichloro-N-[4-(1H-imidazol-1-yl)butyl]benzamide EXAMPLE 64 3,4-Dichloro-N-[4-(1H-imidazol-1-yl)butyl]benzamide A solution of 1.05 g. of 3,4-dichlorobenzoyl chloride in 25 ml. of methylene chloride was added to a stirred solution of 1.06 g. of 1H-imidazole-1-butanamine dihydrochloride in 15 ml. of 1N sodium hydroxide. The mixture was stirred for 18 hours, methylene chloride was added and the layers were separated. The organic layer was washed with water, dried over magnesium sulfate and concentrated. The residue was washed onto a filter with diethyl ether, giving the desired product, m.p. 86°-88° C. Following the procedure of this example and using the appropriate benzoyl chloride, the products of Examples 65-70 were obtained as set forth in Table X below. in sodium hydroxide, dichloromethane Patent; American Cyanamid Company; US4568687; (1986); (A1) English View in Reaxys O Cl

Rx-ID: 31325779 View in Reaxys 46/294 Yield

Conditions & References Reaction Steps: 3 1.1: n-butyllithium / diethyl ether / 4.16 h / -78 - 0 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: potassium permanganate; water; sodium carbonate / 8 h / Reflux 3.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0 - 20 °C / Inert atmosphere With potassium permanganate, n-butyllithium, oxalyl dichloride, water, sodium carbonate, N,N-dimethyl-formamide in diethyl ether, dichloromethane Shacklady-Mcatee, Danielle M.; Dasgupta, Srimoyee; Watson, Mary P.; Organic Letters; vol. 13; nb. 13; (2011); p. 3490 - 3493 View in Reaxys Reaction Steps: 3 1: water-d2 2: potassium permanganate

52/118

2016-07-02 05:35:12

3: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / |Reflux With potassium permanganate, oxalyl dichloride, water-d2 in dichloromethane, N,N-dimethyl-formamide Suess, Alison M.; Ertem, Mehmed Z.; Cramer, Christopher J.; Stahl, Shannon S.; Journal of the American Chemical Society; vol. 135; nb. 26; (2013); p. 9797 - 9804 View in Reaxys O 2H

Cl 2H

Rx-ID: 31325784 View in Reaxys 47/294 Yield

Conditions & References Reaction Steps: 2 1: potassium permanganate; water; sodium carbonate / 8 h / Reflux 2: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 0 - 20 °C / Inert atmosphere With potassium permanganate, oxalyl dichloride, water, sodium carbonate, N,N-dimethyl-formamide in dichloromethane Shacklady-Mcatee, Danielle M.; Dasgupta, Srimoyee; Watson, Mary P.; Organic Letters; vol. 13; nb. 13; (2011); p. 3490 - 3493 View in Reaxys Reaction Steps: 2 1: potassium permanganate 2: oxalyl dichloride / dichloromethane; N,N-dimethyl-formamide / |Reflux With potassium permanganate, oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide Suess, Alison M.; Ertem, Mehmed Z.; Cramer, Christopher J.; Stahl, Shannon S.; Journal of the American Chemical Society; vol. 135; nb. 26; (2013); p. 9797 - 9804 View in Reaxys O

C Cl

Rx-ID: 4995405 View in Reaxys 48/294 Yield

Conditions & References With methyloxirane in cyclohexane, T= 22 °C , Rate constant Pezacki, John Paul; Wood, Paul D.; Gadosy, Timothy A.; Lusztyk, Janusz; Warkentin, John; Journal of the American Chemical Society; vol. 120; nb. 34; (1998); p. 8681 - 8691 View in Reaxys With oxygen in 1,2,2-trifluoro-trichloroethane, T= 20 °C , Kinetics Makihara, Taiki; Nojima, Takayuki; Ishiguro, Katsuya; Sawaki, Yasuhiko; Tetrahedron Letters; vol. 44; nb. 4; (2003); p. 865 - 868 View in Reaxys O

Cl O

O N

Rx-ID: 2076279 View in Reaxys 49/294 Yield 57 %, 19 %

Conditions & References With thionyl chloride in benzene, Time= 1h, Heating Flowers, William T.; Robinson, John F.; Taylor, David R.; Tipping, Anthony E.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1981); p. 349 - 355 View in Reaxys

53/118

2016-07-02 05:35:12

19 %, 57 %

With thionyl chloride in benzene, Time= 1h, Heating Flowers, William T.; Robinson, John F.; Taylor, David R.; Tipping, Anthony E.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1981); p. 349 - 355 View in Reaxys

Cl N

Rx-ID: 3877909 View in Reaxys 50/294 Yield

Conditions & References With oxygen in solid matrix, T= -263.2 °C , Irradiation Sander, Wolfram W.; Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy; vol. 43; nb. 5; (1987); p. 637 - 646 View in Reaxys

(v4)

Pt SP-4

(v4)

Rx-ID: 26635323 View in Reaxys 51/294 Yield

Conditions & References With chlorine in dichloromethane, byproducts: (PPh)2PtCl2; addition of Cl2 to trans-(Pt(PPh3)2(PhCO)Cl) in CH2Cl2; determination:IR Kubota, Mitsuru; Boegeman, Scott C.; Keil, Robert N.; Webb, Carl G.; Organometallics; vol. 8; (1989); p. 1616 1620 ; (from Gmelin) View in Reaxys With cyanogen (pseudo)iodide in dichloromethane, addition of ICN to trans-(Pt(PPh3)2(PhCO)Cl) in CH2Cl2 Kubota, Mitsuru; Boegeman, Scott C.; Keil, Robert N.; Webb, Carl G.; Organometallics; vol. 8; (1989); p. 1616 1620 ; (from Gmelin) View in Reaxys With iodine cloride in dichloromethane, byproducts: (PPh)2PtClI; addition of ICl to trans-(Pt(PPh3)2(PhCO)Cl) in CH2Cl2; determination:IR Kubota, Mitsuru; Boegeman, Scott C.; Keil, Robert N.; Webb, Carl G.; Organometallics; vol. 8; (1989); p. 1616 1620 ; (from Gmelin) View in Reaxys 2

Rx-ID: 305845 View in Reaxys 52/294 Yield

Conditions & References With thionyl chloride Prosser; Eliel; Journal of the American Chemical Society; vol. 79; (1957); p. 2544 View in Reaxys

Na + O–

Rx-ID: 532617 View in Reaxys 53/294

54/118

2016-07-02 05:35:12

Yield

Conditions & References With sulfur dioxide, chlorine Patent; Hoechster Farbw.; DE210805 View in Reaxys With SCl2, T= 20 °C Heintz; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; vol. 98; (1856); p. 464,473 View in Reaxys Carius; Justus Liebigs Annalen der Chemie; vol. 106; (1858); p. 299 View in Reaxys With trichlorophosphate Gerhardt; Annales de Chimie (Cachan, France); vol. <3> 37; (1853); p. 300; Justus Liebigs Annalen der Chemie; vol. 87; (1853); p. 73 View in Reaxys

O Cl

Rx-ID: 9080667 View in Reaxys 54/294 Yield

Conditions & References T= -263.16 °C , Photolysis Nikitina, Asya; Sheridan, Robert S.; Journal of the American Chemical Society; vol. 124; nb. 26; (2002); p. 7670 7671 View in Reaxys

O P

(v4)

Pd SP-4 Cl (v4)

Rx-ID: 26515262 View in Reaxys 55/294 Yield

Conditions & References With cyanogen (pseudo)iodide in dichloromethane, addition of ICN to Pd(P(C6H5)3)2(C6H5CO)Cl in CH2Cl2; determination : IR Kubota, Mitsuru; Boegeman, Scott C.; Keil, Robert N.; Webb, Carl G.; Organometallics; vol. 8; (1989); p. 1616 1620 ; (from Gmelin) View in Reaxys With chlorine in dichloromethane, byproducts: (P(C6H5)3)2PdCl2; addition of Cl2 to Pd(P(C6H5)3)2(C6H5CO)Cl in CH2Cl2; determination : IR Kubota, Mitsuru; Boegeman, Scott C.; Keil, Robert N.; Webb, Carl G.; Organometallics; vol. 8; (1989); p. 1616 1620 ; (from Gmelin) View in Reaxys 2H

2H 2H

Cl 2H

Rx-ID: 34411166 View in Reaxys 56/294

55/118

2016-07-02 05:35:12

Yield

Conditions & References Reaction Steps: 2 1: potassium permanganate; sodium carbonate / water / 8 h / |Reflux 2: oxalyl dichloride; DMFA / dichloromethane / 4 h / 20 °C / |Inert atmosphere With potassium permanganate, oxalyl dichloride, sodium carbonate, DMFA in dichloromethane, water Zhang, Nana; Li, Binyao; Zhong, Hongban; Huang, Jianhui; Organic and Biomolecular Chemistry; vol. 10; nb. 47; (2012); p. 9429 - 9439 View in Reaxys Reaction Steps: 2 1: potassium permanganate; sodium carbonate / water / 8 h / 120 °C / |Inert atmosphere; |Schlenk technique 2: DMFA; oxalyl dichloride / dichloromethane / 4 h / 20 °C / |Inert atmosphere; |Schlenk technique With potassium permanganate, oxalyl dichloride, sodium carbonate, DMFA in dichloromethane, water Gandeepan, Parthasarathy; Rajamalli, Pachaiyappan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 55; nb. 13; (2016); p. 4308 - 4311; Angew. Chem.; vol. 128; (2016); p. 4380 - 4383,4 View in Reaxys O

Rx-ID: 41196924 View in Reaxys 57/294 Yield

Conditions & References Stage 1: With pyridine, sulfur monochloride in chlorobenzene, Time= 2.5h, T= 75 °C Stage 2: in chlorobenzene, Time= 19h, T= 137 °C Zaragoza, Florencio; Journal of Organic Chemistry; vol. 80; nb. 20; (2015); p. 10370 - 10374 View in Reaxys O

O HN O

N O

O O

O N

O O

Rx-ID: 24139039 View in Reaxys 58/294 Yield

Conditions & References 8.a : 2-(Benzoyloxymethyl)-7,8-dimethoxy-4 (5H), 10-dioxo-2H-1,2,3-triazolo[4,5-c][1]benzazepine (8a) In the same manner as in Example 3 (3a), provided that benzoyl chloride (0.28 ml) was used instead of ethyl chloroformate, a crude product of ethyl 2-(benzoyloxymethyl)-5-(4,5-dimethoxy-2-nitrobenzoyl)-2H-1,2,3-triazole-4-carboxylate (230 mg) was prepared as a light yellow oil from ethyl 5-(4,5-dimethoxy-2-nitrobenzoyl)-1H-1,2,3-triazole-4-carboxylate (Synthesis Example 2) (210 mg) Patent; Meiji Seika Kaisha, Ltd.; US6372735; (2002); (B1) English View in Reaxys

OH HO

S OO

Cl Cl

O O

Rx-ID: 25119222 View in Reaxys 59/294 Yield

Conditions & References 9 : EXAMPLE 9 EXAMPLE 9 2,500 g (14.8 mols) of a 93.8percent pure benzenesulphonic acid which has been prepared by sulphonation of benzene with SO3 and contains 1.8percent by weight of H2 SO4 is reacted with 3,093 g (15.6 mols) of benzotrichloride (98.5percent pure) at 110° C. analogously to Example 4. Distillation is carried out under 10 mbars over a 1 m mirrored column (φ 5 cm, packing: 5*5 mm Raschig rings).

56/118

2016-07-02 05:35:12

Yield: benzoyl chloride: 93.6percent; benzenesulphonyl chloride: 85.9percent. Patent; Bayer Aktiengesellschaft; US4349471; (1982); (A1) English View in Reaxys 13 : EXAMPLE 13 EXAMPLE 13 977.5 g (5 mols) of benzotrichloride (98.5percent pure) are added, in the course of one hour at 95° C., to 841.5 g (5 mols) of a 94percent pure benzenesulphonic acid which has been prepared by sulphonation of benzene with SO3 and contains 1.8percent of H2 SO4. The mixture is then subsequently stirred at 95° C. for one hour. Distillation is carried out under 10 mbar over a mirrored column (3 cm*30 cm). Yield: benzoyl chloride: 96.3percent; benzenesulphonyl chloride: 87.8percent. Patent; Bayer Aktiengesellschaft; US4349471; (1982); (A1) English View in Reaxys

N H N N

O N

Rx-ID: 25135253 View in Reaxys 60/294 Yield

Conditions & References 21 : EXAMPLE 21 EXAMPLE 21 Following the procedure described in Example 20 but starting from 3-phenyl-6-(1,2,3,4-tetrahydro-2-isoquinolyl)methyl-5,6-dihydro-4H-1,2,4-oxadiazine and benzoyl chloride, 3-phenyl-4-benzoyl-6-(1,2,3,4-tetrahydro-2-isoquinolyl)-methyl-5,6-dihydro-1,2,4-oxadiazine is obtained, melting at 174° to 175° C., after recrystallization from isopropanol. Analysis for C26 H25 N3 O2: calculated: C=75.89percent; H=6.12percent; N=10.21percent; found: C=75.80percent; H=6.13percent; N=9.98percent. Patent; Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Rt; US4308270; (1981); (A1) English View in Reaxys

P (v4) Pt SP-4

(v4) (v4)

Rx-ID: 26635270 View in Reaxys 61/294 Yield

Conditions & References With chlorine in dichloromethane, byproducts: (PPh)2PtClBr; addition of Cl2 to trans-(Pt(PPh3)2(PhCO)Br) in CH2Cl2; determination:IR Kubota, Mitsuru; Boegeman, Scott C.; Keil, Robert N.; Webb, Carl G.; Organometallics; vol. 8; (1989); p. 1616 1620 ; (from Gmelin) View in Reaxys O

Cl Nb

Cl (v5) Cl

O O

Rx-ID: 3003788 View in Reaxys 62/294

57/118

2016-07-02 05:35:12

Yield

Conditions & References

70 %

With water, Yields of byproduct given Kauffmann, Thomas; Abel, Thomas; Beirich, Christoph; Kieper, Gudrun; Pahde, Claudia; et al.; Tetrahedron Letters; vol. 27; nb. 44; (1986); p. 5355 - 5358 View in Reaxys

O–

13C

Na +

13C

Rx-ID: 3492408 View in Reaxys 63/294 Yield

Conditions & References With trichlorophosphate Liguori, Angelo; Sindona, Giovanni; Uccella, Nicola; Journal of Organic Chemistry; vol. 46; nb. 22; (1981); p. 4450 - 4453 View in Reaxys With pyridine, oxalyl dichloride in benzene, Time= 1h, Substitution Young, David J.; Robinson, Michael J.T.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 43; nb. 2; (2000); p. 121 - 126 View in Reaxys

O Cl Cl

Rx-ID: 29483893 View in Reaxys 64/294 Yield

Conditions & References

31.9 mg

With N-ethyl-N,N-diisopropylamine in dichloromethane, Time= 0.0833333h, T= 20 °C , Inert atmosphere Hardee, David J.; Kovalchuke, Lyudmila; Lambert, Tristan H.; Journal of the American Chemical Society; vol. 132; nb. 14; (2010); p. 5002 - 5003 View in Reaxys

O N

N H

N S

Rx-ID: 1994849 View in Reaxys 65/294 Yield 30 %

Conditions & References With thionyl chloride in benzene, Time= 5h, Heating, Yields of byproduct given Flowers, William T.; Robinson, John F.; Taylor, David R.; Tipping, Anthony E.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1981); p. 349 - 355 View in Reaxys O

C O

Rx-ID: 2057704 View in Reaxys 66/294 Yield

Conditions & References With tetrachloromethane, T= 24 °C , other quenchers, Rate constant Neville; Brown; Rayner; Lusztyk; Ingold; Journal of the American Chemical Society; vol. 113; nb. 5; (1991); p. 1869 - 1870 View in Reaxys With tetrachloromethane in hexane, T= 22.9 °C , Rate constant

58/118

2016-07-02 05:35:12

Brown, Carl E.; Neville, Anthony G.; Rayner, David M.; Ingold, Keith U.; Lusztyk, Janusz; Australian Journal of Chemistry; vol. 48; nb. 2; (1995); p. 363 - 380 View in Reaxys

O+

O Cl

O Cl –

Cl N

Rx-ID: 2656339 View in Reaxys 67/294 Yield

Conditions & References

89 %

With hydrogenchloride in toluene, Heating Schroth,Werner; Spitzner, Roland; Tetrahedron Letters; vol. 26; nb. 33; (1985); p. 3963 - 3966 View in Reaxys

89 %

With hydrogenchloride in toluene, Heating, reactivity of 2-acyl-1-chlor-enamines, Mechanism Schroth,Werner; Spitzner, Roland; Tetrahedron Letters; vol. 26; nb. 33; (1985); p. 3963 - 3966 View in Reaxys

O O

Rx-ID: 857574 View in Reaxys 68/294 Yield

Conditions & References With phosphorus pentachloride, Petroleum ether Reijnhart; Recueil des Travaux Chimiques des Pays-Bas; vol. 46; (1927); p. 62 View in Reaxys With phosphorus pentachloride, T= 96 - 98 °C Reijnhart; Recueil des Travaux Chimiques des Pays-Bas; vol. 46; (1927); p. 62 View in Reaxys

Cl N

O Cl

O O

Cl O

(v4)

Cl O

O3, CO2 O

Rx-ID: 6730168 View in Reaxys 69/294 Yield

Conditions & References With oxygen, T= -247.2 °C , p= 150 - 200Torr , Irradiation, study of the oxygen trapping of phenylchlorocarbene intermediate formed from phenylchlorodiazirine in oxigen-doped matrix by irradiation, mechanism is discussed, Product distribution, Mechanism Ganzer, Georg A.; Sheridan, Robert S.; Liu, Michael T. H.; Journal of the American Chemical Society; vol. 108; nb. 7; (1986); p. 1517 - 1520 View in Reaxys H 13C 13CH 13

H 13C 13CH

H 13C 13

H 13C

CH 13

13CH

Rx-ID: 15927227 View in Reaxys 70/294

59/118

2016-07-02 05:35:12

Yield

Conditions & References Reaction Steps: 2 1: 4.37 g / NaOBr / H2O / 3 h 2: thionyl chloride / benzene / 3 h / Heating With thionyl chloride, sodium hypobromide in water, benzene, 1: Oxidation / 2: Chlorination Breuer, Stephen W.; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 43; nb. 3; (2000); p. 283 286 View in Reaxys

H 2N

(S)-2-chloro-butyric acid Rx-ID: 18439452 View in Reaxys 71/294 Yield

Conditions & References Reaction Steps: 2 1: 86 percent / TiCl4 / dioxane; H2O / 19 h / Heating 2: oxalyl chloride / CH2Cl2 / 0 - 20 °C With oxalyl dichloride, titanium tetrachloride in 1,4-dioxane, dichloromethane, water Fisher; Caroon; Stabler; Lundberg; Zaidi; Sorensen; Sparacino; Muchowski; Canadian Journal of Chemistry; vol. 72; nb. 1; (1994); p. 142 - 145 View in Reaxys

(S)-2-chloro-butyric acid Rx-ID: 18466009 View in Reaxys 72/294 Yield

Conditions & References Reaction Steps: 3 1: aq. NH4OH / CH2Cl2 / 0 - 20 °C 2: 86 percent / TiCl4 / dioxane; H2O / 19 h / Heating 3: oxalyl chloride / CH2Cl2 / 0 - 20 °C With ammonium hydroxide, oxalyl dichloride, titanium tetrachloride in 1,4-dioxane, dichloromethane, water Fisher; Caroon; Stabler; Lundberg; Zaidi; Sorensen; Sparacino; Muchowski; Canadian Journal of Chemistry; vol. 72; nb. 1; (1994); p. 142 - 145 View in Reaxys

(S)-2-chloro-butyric acid Rx-ID: 18467177 View in Reaxys 73/294 Yield

Conditions & References Reaction Steps: 4 1: oxalyl chloride / CH2Cl2 / 0 - 20 °C 2: aq. NH4OH / CH2Cl2 / 0 - 20 °C 3: 86 percent / TiCl4 / dioxane; H2O / 19 h / Heating 4: oxalyl chloride / CH2Cl2 / 0 - 20 °C With ammonium hydroxide, oxalyl dichloride, titanium tetrachloride in 1,4-dioxane, dichloromethane, water Fisher; Caroon; Stabler; Lundberg; Zaidi; Sorensen; Sparacino; Muchowski; Canadian Journal of Chemistry; vol. 72; nb. 1; (1994); p. 142 - 145 View in Reaxys O O

Cl O

O Cl

Rx-ID: 29389250 View in Reaxys 74/294

60/118

2016-07-02 05:35:12

Yield

Conditions & References

28 %Spectr., 26 %Spectr.

With tetrachloromethane, Time= 7h, T= 250 °C , Inert atmosphere, Autoclave Tanemura, Kiyoshi; Suzuki, Tsuneo; Nishida, Yoko; Horaguchi, Takaaki; Tetrahedron; vol. 66; nb. 15; (2010); p. 2881 - 2888 View in Reaxys

Rx-ID: 29389259 View in Reaxys 75/294 Yield

Conditions & References

64 %Spectr., 15 %Spectr.

O O

Cl O

Rx-ID: 87313 View in Reaxys 76/294 Yield

Conditions & References With hydrogenchloride, Chromium (III) chloride, T= 290 - 300 °C Patent; Monsanto Chem. Co.; US2006335; (1929) View in Reaxys O

O O

Rx-ID: 281519 View in Reaxys 77/294 Yield

Conditions & References With phosphorus pentachloride, T= 140 °C , im geschlossenen Rohr Michael; American Chemical Journal; vol. 9; (1887); p. 215; Journal fuer Praktische Chemie (Leipzig); vol. <2>35; (1887); p. 96 View in Reaxys

Rx-ID: 601476 View in Reaxys 78/294 Yield

P N

Cl Cl

Cl P

N Cl

Rx-ID: 4182696 View in Reaxys 79/294

61/118

2016-07-02 05:35:12

Yield

Conditions & References

50 %

With phosphonitrilic chloride trimer, triethylamine in acetonitrile, Time= 1.5h, T= 20 °C , Mechanism Vapirov, V.V.; Tunina, S.G.; Rodina, L.L.; Russian Journal of Organic Chemistry; vol. 30; nb. 2; (1994); p. 320 322; Zhurnal Organicheskoi Khimii; vol. 30; nb. 2; (1994); p. 302 - 303 View in Reaxys O

H 13 2 C

13C

Rx-ID: 4991649 View in Reaxys 80/294 Yield

Conditions & References With Ph3PCl(+)Cl(-) in dichloromethane, Time= 24h, Ambient temperature Katritzky, Alan R.; Voronkov, Michael V.; Toader, Dorin; Journal of the Chemical Society. Perkin Transactions 2; nb. 11; (1998); p. 2515 - 2518 View in Reaxys O O

N-<4-oxy-benzyliden>-aniline

lead sulfide Cl

Rx-ID: 20550846 View in Reaxys 81/294 Yield

Conditions & References Reaction Steps: 3 1: hydrazine hydrate 3: thionyl chloride / benzene / 1 h / Heating With thionyl chloride, hydrazine hydrate in benzene Flowers, William T.; Robinson, John F.; Taylor, David R.; Tipping, Anthony E.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1981); p. 349 - 355 View in Reaxys O

alkaline NaOCl H 2N

lead sulfide Cl

Rx-ID: 20560663 View in Reaxys 82/294 Yield

Conditions & References Reaction Steps: 2 2: thionyl chloride / benzene / 1 h / Heating With thionyl chloride in benzene Flowers, William T.; Robinson, John F.; Taylor, David R.; Tipping, Anthony E.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1981); p. 349 - 355 View in Reaxys 2H

OH H 13C

13CH

H 13C

13CH

Rx-ID: 32978426 View in Reaxys 83/294 Yield

Conditions & References Reaction Steps: 4 1: potassium carbonate / acetone 2: palladium on activated charcoal; sodium carbonate; deuterium / benzene 3: methanol; sodium hydroxide

62/118

2016-07-02 05:35:12

4: thionyl chloride With methanol, thionyl chloride, palladium on activated charcoal, sodium carbonate, potassium carbonate, deuterium, sodium hydroxide in acetone, benzene Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, Jungoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune; Journal of Biomolecular NMR; vol. 51; nb. 4; (2011); p. 425 - 435 View in Reaxys 2H

OH H 13C 2H

13CH 13C

H 13C 2H

13CH 13C

Rx-ID: 32978437 View in Reaxys 84/294 Yield

Conditions & References Reaction Steps: 4 1: potassium carbonate / acetone 2: palladium on activated charcoal; sodium carbonate; deuterium / benzene 3: methanol; sodium hydroxide 4: thionyl chloride With methanol, thionyl chloride, palladium on activated charcoal, sodium carbonate, potassium carbonate, deuterium, sodium hydroxide in acetone, benzene Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, Jungoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune; Journal of Biomolecular NMR; vol. 51; nb. 4; (2011); p. 425 - 435 View in Reaxys

N N

H 13C

O 13

H C 2H

13C

13CH 13C

Rx-ID: 32978448 View in Reaxys 85/294 Yield

Conditions & References Reaction Steps: 3 1: palladium on activated charcoal; sodium carbonate; deuterium / benzene 2: methanol; sodium hydroxide 3: thionyl chloride With methanol, thionyl chloride, palladium on activated charcoal, sodium carbonate, deuterium, sodium hydroxide in benzene Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, Jungoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune; Journal of Biomolecular NMR; vol. 51; nb. 4; (2011); p. 425 - 435 View in Reaxys

63/118

2016-07-02 05:35:12

N N

H 13C

13CH

Rx-ID: 32978503 View in Reaxys 86/294 Yield

H 2N

Cl Br

Rx-ID: 34588507 View in Reaxys 87/294 Yield

Conditions & References Reaction Steps: 4 1.1: hydrogenchloride; sodium nitrite; potassium iodide / water / 1.5 h / 0 - 70 °C / |Schlenk technique; |Inert atmosphere 2.1: isopropylmagnesium chloride / tetrahydrofuran; diethyl ether / 2 h / -78 °C / |Inert atmosphere; |Schlenk technique 2.2: 0.5 h / 20 °C / |Inert atmosphere; |Schlenk technique 3.1: n-butyllithium / tetrahydrofuran; hexane / 0.67 h / 78 °C / |Inert atmosphere; |Schlenk technique 3.2: 0.17 h / -78 - 20 °C 4.1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 4 h / 0 - 20 °C / |Inert atmosphere; |Schlenk technique With hydrogenchloride, n-butyllithium, oxalyl dichloride, isopropylmagnesium chloride, N,N-dimethyl-formamide, potassium iodide, sodium nitrite in tetrahydrofuran, diethyl ether, hexane, dichloromethane, water Karthikeyan, Jaganathan; Haridharan, Radhakrishnan; Cheng, Chien-Hong; Angewandte Chemie - International Edition; vol. 51; nb. 49; (2012); p. 12343 - 12347; Angew. Chem.; vol. 124; nb. 49; (2012); p. 12509 - 12513,4 View in Reaxys

Cl Cl

Rx-ID: 666162 View in Reaxys 88/294 Yield

Conditions & References With zinc(II) chloride, T= 120 °C Patent; Dow Chem.Co.; US1921767; (1929) View in Reaxys Rabcewicz-Zubkowski; Roczniki Chemii; vol. 10; p. 547; Chem. Zentralbl.; vol. 101; nb. II; (1930); p. 3273 View in Reaxys

64/118

2016-07-02 05:35:12

Rx-ID: 666323 View in Reaxys 89/294 Yield

Conditions & References With ethanol, iron(III) chloride, T= 130 - 140 °C Patent; Verein f. chem. u. metallurg. Produktion in Aussig; DE472422; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 16; p. 419 View in Reaxys

O O

O Cl

Rx-ID: 857575 View in Reaxys 90/294 Yield

Conditions & References With phosphorus pentachloride, T= 96 - 98 °C Reijnhart; Recueil des Travaux Chimiques des Pays-Bas; vol. 46; (1927); p. 62 View in Reaxys Br

O Cl

Rx-ID: 2061498 View in Reaxys 91/294 Yield

Conditions & References With α,α,α-trichlorotoluene, iron(III) chloride in benzene, T= 55 °C , ΔE(excit.), Product distribution, Rate constant, Thermodynamic data Freidlin, E. G.; Journal of Organic Chemistry USSR (English Translation); vol. 17; nb. 6; (1981); p. 1129 - 1132; Zhurnal Organicheskoi Khimii; vol. 17; nb. 6; (1981); p. 1275 - 1279 View in Reaxys

O Cl

Rx-ID: 2103250 View in Reaxys 92/294 Yield

O N H

Cl N

Rx-ID: 2826046 View in Reaxys 93/294 Yield

Conditions & References With thionyl chloride in benzene, Time= 8h, Heating, Yield given. Yields of byproduct given Flowers, William T.; Robinson, John F.; Taylor, David R.; Tipping, Anthony E.; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); (1981); p. 349 - 355 View in Reaxys

65/118

2016-07-02 05:35:12

Rx-ID: 2948851 View in Reaxys 94/294 Yield

O O

Rx-ID: 2963010 View in Reaxys 95/294 Yield

Conditions & References With α,α,α-trichlorotoluene, iron(III) chloride in benzene, T= 55 °C , ΔE(excit.), var. temp., Product distribution, Rate constant, Thermodynamic data Freidlin, E. G.; Journal of Organic Chemistry USSR (English Translation); vol. 17; nb. 6; (1981); p. 1129 - 1132; Zhurnal Organicheskoi Khimii; vol. 17; nb. 6; (1981); p. 1275 - 1279 View in Reaxys

O O

Rx-ID: 3865894 View in Reaxys 96/294 Yield

O Cl

Rx-ID: 3929011 View in Reaxys 97/294 Yield

Cl SiH

O HO

O O

Rx-ID: 11178104 View in Reaxys 98/294 Yield

Conditions & References With indium(III) chloride in 1,2-dichloro-ethane, Time= 4h, T= 80 °C , Product distribution, Further Variations: Temperatures, Reagents Babu, Srinivasarao Arulananda; Yasuda, Makoto; Baba, Akio; Organic Letters; vol. 9; nb. 3; (2007); p. 405 - 408 View in Reaxys

66/118

2016-07-02 05:35:12

H 2N

N O

Rx-ID: 37348251 View in Reaxys 99/294 Yield

Conditions & References With oxalyl dichloride in dichloromethane, N,N-dimethyl-formamide Shang, Ming; Sun, Shang-Zheng; Dai, Hui-Xiong; Yu, Jin-Quan; Journal of the American Chemical Society; vol. 136; nb. 9; (2014); p. 3354 - 3357 View in Reaxys

O P

(v4)

Cl (v4)

(v4)

P (v4) O PdI SP-4 (v4) P

Pd SP-4

Rx-ID: 35274479 View in Reaxys 100/294 Yield

Conditions & References in benzene-d6, T= 20 °C , Glovebox Kuniyasu, Hitoshi; Sanagawa, Atsushi; Nakane, Daisuke; Iwasaki, Takanori; Kambe, Nobuaki; Bobuatong, Karan; Lu, Yunpeng; Ehara, Masahiro; Organometallics; vol. 32; nb. 6; (2013); p. 2026 - 2032 View in Reaxys

P (v4)

(v4)

Pt SP-4

(v4)

Pt SP-4

(v4)

Rx-ID: 35274491 View in Reaxys 101/294 Yield

Conditions & References in benzene-d6, Time= 0.416667h, T= 20 °C , Glovebox Kuniyasu, Hitoshi; Sanagawa, Atsushi; Nakane, Daisuke; Iwasaki, Takanori; Kambe, Nobuaki; Bobuatong, Karan; Lu, Yunpeng; Ehara, Masahiro; Organometallics; vol. 32; nb. 6; (2013); p. 2026 - 2032 View in Reaxys

Cl N

O N

O C

O Cl

Rx-ID: 2651322 View in Reaxys 102/294 Yield

Conditions & References in various solvent(s), T= -263.2 °C , Irradiation, followed by IR, Product distribution Kesselmayer, Mark A.; Sheridan, Robert S.; Journal of the American Chemical Society; vol. 108; nb. 4; (1986); p. 844 - 845 View in Reaxys

67/118

2016-07-02 05:35:12

O Cl

P O

O P O

Rx-ID: 8890780 View in Reaxys 103/294 Yield

Conditions & References

78 %

Gazizov; Kachalova; Pudovik; Karimova; Sinyashin; Sadykova; Musin; Russian Journal of General Chemistry; vol. 71; nb. 3; (2001); p. 486 - 487 View in Reaxys OH

N H O

Rx-ID: 10490665 View in Reaxys 104/294 Yield

Conditions & References With tetrachloromethane, T= 100 °C Tarkhanova; Gantman; Chizhov; Smirnov; Russian Chemical Bulletin; vol. 55; nb. 9; (2006); p. 1624 - 1630 View in Reaxys 3H

O 3H

HO 3H

Rx-ID: 5071125 View in Reaxys 105/294 Yield

Conditions & References With thionyl chloride, Substitution Oohashi, Kunio; Nogawa, Norio; Makide, Yoshihiro; Morikawa, Naotake; Izumo, Misiroku; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 41; nb. 10; (1998); p. 951 - 957 View in Reaxys

17O

13C

H 17O

Yield

Conditions & References

Rx-ID: 8777310 View in Reaxys 106/294 With thionyl chloride, Time= 1h, Heating Wu, Gang; Dong, Shuan; Chemical Physics Letters; vol. 334; nb. 4-6; (2001); p. 265 - 270 View in Reaxys O O

O Cl

Rx-ID: 309961 View in Reaxys 107/294 Yield

Conditions & References With chlorine Patent; California Research Corp.; US2865959; (1955) View in Reaxys

Cl Cl

Rx-ID: 642055 View in Reaxys 108/294

68/118

2016-07-02 05:35:12

Yield

Conditions & References T= 100 °C Nessmejanow; Kahn; Chemische Berichte; vol. 67; (1934); p. 370,372; Zhurnal Obshchei Khimii; vol. 4; (1934); p. 1243,1245; Chem. Zentralbl.; vol. 107; nb. I; (1936); p. 4287 View in Reaxys Patent; Dow Chem. Co.; US1921767; (1929) View in Reaxys O

O O

O Cl

Rx-ID: 674368 View in Reaxys 109/294 Yield

Conditions & References With chlorine, phosphorus trichoride Patent; Monsanto Chem. Co.; US1974845; (1931) View in Reaxys

Rx-ID: 757708 View in Reaxys 110/294 Yield

Conditions & References With tungsten(IV) oxide, benzene Patent; Du Pont de Nemours and Co.; US2749366; (1952) View in Reaxys Patent; Du Pont de Nemours and Co.; DE965322; (1953) View in Reaxys

Rx-ID: 757720 View in Reaxys 111/294 Yield

Conditions & References T= 100 - 175 °C , Behandeln des Reaktionsgemisches mit Chlor bei 165grad Patent; Imp. Chem. Ind.; US1880169; (1928) View in Reaxys Patent; Imp. Chem. Ind.; DE543365; (1928); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 18; p. 527 View in Reaxys

Cl O

O Cl

Rx-ID: 846682 View in Reaxys 112/294 Yield

Conditions & References With aluminium trichloride Wilson; Fuller; ; vol. 14; (1922); p. 407; Chem. Zentralbl.; vol. 93; nb. III; (1922); p. 497 View in Reaxys Friedel; Crafts; Ador; Chemische Berichte; vol. 10; (1877); p. 1857; Annales de Chimie (Cachan, France); vol. <6> 1; (1884); p. 521 View in Reaxys

69/118

2016-07-02 05:35:12

Rx-ID: 3384335 View in Reaxys 113/294 Yield

Conditions & References With thionyl chloride, 1) pyridin, 2) heating, Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts Adiwidjaja, Gunadi; Guenther, Horst; Voss, Juergen; Angewandte Chemie; vol. 92; nb. 7; (1980); p. 559 - 561 View in Reaxys With thionyl chloride, 1) pyridin, 2) heating, Yield given. Multistep reaction. Title compound not separated from byproducts Adiwidjaja, Gunadi; Guenther, Horst; Voss, Juergen; Angewandte Chemie; vol. 92; nb. 7; (1980); p. 559 - 561 View in Reaxys

Rx-ID: 4869482 View in Reaxys 114/294 Yield

Conditions & References With N,N-dimethyl-formamide in benzene, T= 20 - 40 °C , ΔH(act.), ΔS(act.); chlorodehydration of benzoic acids with carbonyl chloride in the presence of DMF; rates; kinetics and mechanism, Rate constant, Thermodynamic data Vulakh; Militsin; Russian Journal of Organic Chemistry; vol. 32; nb. 11; (1996); p. 1704 - 1705 View in Reaxys

Cl Cl

sodium-salt of/the/ 3-nitro-benzene-sulfonic acid-(1)

Rx-ID: 5820039 View in Reaxys 115/294 Yield

Conditions & References T= 180 - 200 °C Patent; I.G. Farbenind.; US2016784; (1932) View in Reaxys

Cl Cl

sodium-salt of/the/ methanesulfonic acid Cl

Rx-ID: 5820040 View in Reaxys 116/294 Yield

Conditions & References T= 180 - 200 °C Patent; I.G. Farbenind.; US2016784; (1932) View in Reaxys

Cl Cl

sodium-salt of/the/ naphthalene-sulfonic acid-(2) Cl

Rx-ID: 5820041 View in Reaxys 117/294 Yield

Conditions & References T= 180 - 200 °C Patent; I.G. Farbenind.; US2016784; (1932) View in Reaxys

70/118

2016-07-02 05:35:12

sodium-salt of/the/ toluene-sulfonic acid-(4)

Rx-ID: 5820042 View in Reaxys 118/294 Yield

Conditions & References T= 180 - 200 °C Patent; I.G. Farbenind.; US2016784; (1932) View in Reaxys O

(+-)-benzoic acid-<1.2-dichloro-ethyl ester>

Rx-ID: 5820047 View in Reaxys 119/294 Yield

Conditions & References With zinc(II) chloride Patent; Soc. Usines Chim. Rhone-Poulenc; DE527874; (1929); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 18; p. 796 View in Reaxys

O E

chlorobenzyldeoxybenzoin

Rx-ID: 7056596 View in Reaxys 120/294 Yield

Conditions & References T= 190 - 200 °C Knoevenagel; Chemische Berichte; vol. 26; (1893); p. 448 View in Reaxys

O E

p-tolyl-desyl-chloromethane

Rx-ID: 7056597 View in Reaxys 121/294 Yield

Conditions & References p= 30Torr , durch Destillation Klages; Tetzner; Chemische Berichte; vol. 35; (1902); p. 3970 View in Reaxys

<4-isopropyl-phenyl>-desyl-chloromethane Cl

Rx-ID: 7443734 View in Reaxys 122/294 Yield

Conditions & References T= 200 °C Klages; Tetzner; Chemische Berichte; vol. 35; (1902); p. 3970 View in Reaxys Cl

β-chloro-α-phenyl-β-<4-chloro-phenyl>-propiophenone

Rx-ID: 7917262 View in Reaxys 123/294 Yield

Conditions & References p= 22Torr , durch Destillation

71/118

2016-07-02 05:35:12

Klages; Tetzner; Chemische Berichte; vol. 35; (1902); p. 3970 View in Reaxys 2

H 2

H 13C

13CH

H 13C 2H

13CH

2H 2H

O O

Rx-ID: 32978408 View in Reaxys 124/294 Yield

Conditions & References Reaction Steps: 2 1: methanol; sodium hydroxide 2: thionyl chloride With methanol, thionyl chloride, sodium hydroxide Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, Jungoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune; Journal of Biomolecular NMR; vol. 51; nb. 4; (2011); p. 425 - 435 View in Reaxys 2H

H 13C 2H

2H 13CH

13C

H 13C 2H

13CH 13C

Rx-ID: 32978456 View in Reaxys 125/294 Yield

Conditions & References With thionyl chloride Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, Jungoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune; Journal of Biomolecular NMR; vol. 51; nb. 4; (2011); p. 425 - 435 View in Reaxys 2H 2H

H 13C

13CH

H 13C 2H

13C

13CH

2H 13C

O O

Rx-ID: 32978471 View in Reaxys 126/294 Yield

H 13C 2H

2H 13CH 2H

H 13C

13CH

Rx-ID: 32978512 View in Reaxys 127/294 Yield

Conditions & References With thionyl chloride

72/118

2016-07-02 05:35:12

Miyanoiri, Yohei; Takeda, Mitsuhiro; Jee, Jungoo; Ono, Akira M.; Okuma, Kosuke; Terauchi, Tsutomu; Kainosho, Masatsune; Journal of Biomolecular NMR; vol. 51; nb. 4; (2011); p. 425 - 435 View in Reaxys 18O

N Cl

Rx-ID: 42394980 View in Reaxys 128/294 Yield

Conditions & References Reaction Steps: 2 1: 18O-labeled water; hydrogenchloride / 20 h / 100 °C 2: thionyl chloride / 1 h / 80 °C With hydrogenchloride, thionyl chloride, 18O-labeled water Zu, Chengli; Mukhopadhyay, Sukrit; Hanley, Patrick S.; Xia, Shijing; Bell, Bruce M.; Grigg, David; Gilbert, Jeffrey R.; OBrien, John P.; Journal of the American Society for Mass Spectrometry; vol. 27; nb. 5; (2016); p. 917 926 View in Reaxys

O–

O K+

Rx-ID: 61285 View in Reaxys 129/294 Yield

Conditions & References T= 250 °C Patent; Monsanto Chem. Co.; US2806061; (1955) View in Reaxys

O O S

S Cl

Rx-ID: 72417 View in Reaxys 130/294 Yield

Conditions & References With tetrachloromethane, chlorine Boehme; Clement; Justus Liebigs Annalen der Chemie; vol. 576; (1952); p. 61,67 View in Reaxys O

Rx-ID: 303343 View in Reaxys 131/294 Yield

Conditions & References With tetrachloromethane, chlorine Boehme; Clement; Justus Liebigs Annalen der Chemie; vol. 576; (1952); p. 61,67 View in Reaxys O O S

N O

O S

N O

Rx-ID: 314302 View in Reaxys 132/294

73/118

2016-07-02 05:35:12

Yield

Conditions & References With tetrachloromethane, chlorine Fries; Justus Liebigs Annalen der Chemie; vol. 454; (1927); p. 306 View in Reaxys O

O Cl

Rx-ID: 601768 View in Reaxys 133/294 Yield

Conditions & References With chlorine Laurent; Gerhardt; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1850); p. 488 View in Reaxys

Cl H

Rx-ID: 666165 View in Reaxys 134/294 Yield

Conditions & References T= 100 °C Gavankar; Heble; Wheeler; Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine; vol. 6; (1937); p. 112; Chem. Zentralbl.; vol. 109; nb. I; (1938); p. 4610 View in Reaxys

Cl O

Rx-ID: 757712 View in Reaxys 135/294 Yield

Conditions & References T= 140 - 160 °C Prat; ; vol. 34; (1948); p. 381; ; (1950); p. 5843 View in Reaxys

sodium-<toluene sulfonate-(4)> Cl

O Cl

S Cl

Rx-ID: 5932818 View in Reaxys 136/294 Yield

Conditions & References T= 200 °C Patent; I.G. Farbenind.; DE574836; (1931); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 19; p. 627 View in Reaxys

Cl O

Rx-ID: 9684705 View in Reaxys 137/294 Yield

Conditions & References in dichloromethane, Flash photolysis Showalter, Brett M.; Toscane, John P.; Journal of Physical Organic Chemistry; vol. 17; nb. 9; (2004); p. 743 - 748 View in Reaxys

74/118

2016-07-02 05:35:12

Rx-ID: 65434 View in Reaxys 138/294 Yield

Conditions & References With water, T= 140 °C , Einleiten von Chlor in das Reaktionsgemisch, zuletzt bei 200grad Patent; Imp. Chem. Ind.; US1880169; (1928) View in Reaxys Patent; Imp. Chem. Ind.; DE543365; (1928); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 18; p. 527 View in Reaxys Durchleiten von Sauerstoff im UV-Licht Mueller; Ehrmann; Chemische Berichte; vol. 69; (1936); p. 2210 View in Reaxys 2H

O 2H

Cl 2H

Rx-ID: 8997025 View in Reaxys 139/294 Yield

Conditions & References Turro, Nicholas J.; Lei, Xue-Gong; Jockusch, Steffen; Li, Wei; Liu, Zhiqiang; Abrams, Lloyd; Ottaviani, M. Francesca; Journal of Organic Chemistry; vol. 67; nb. 8; (2002); p. 2606 - 2618 View in Reaxys O

F Cl

O Cl

Rx-ID: 33271079 View in Reaxys 140/294 Yield

Conditions & References T= 20 °C Basenko; Voronkov; Zelenkov; Albanov; Doklady Chemistry; vol. 439; nb. 2; (2011); p. 219 - 222 View in Reaxys Cl

O O

N O

Rx-ID: 3877910 View in Reaxys 141/294 Yield

Conditions & References With oxygen in solid matrix, T= -263.2 °C , Irradiation, different O2 concentrations and wavelengths of irradiation, Product distribution, Mechanism Sander, Wolfram W.; Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy; vol. 43; nb. 5; (1987); p. 637 - 646 View in Reaxys O

Cl Cl

Rx-ID: 4827323 View in Reaxys 142/294 Yield

Conditions & References With lithium in tetrahydrofuran, T= 25 - 37.5 °C , trapping experiment for evidence for radical intermediates, Product distribution, Mechanism

75/118

2016-07-02 05:35:12

Nudelman; Mendiara, Sara; Journal of Physical Organic Chemistry; vol. 10; nb. 4; (1997); p. 233 - 241 View in Reaxys O

Na +

chlorosulfonate sodium

O–

Rx-ID: 5820034 View in Reaxys 143/294 Yield

Conditions & References Patent; Bad. Anilin- u. Sodaf.; DE146690 View in Reaxys Heumann; Koechlin; Chemische Berichte; vol. 15; (1882); p. 1116 View in Reaxys

chlorosulfonate sodium HO

Rx-ID: 5820035 View in Reaxys 144/294 Yield

Conditions & References Patent; Bad. Anilin- u. Sodaf.; DE146690 View in Reaxys Heumann; Koechlin; Chemische Berichte; vol. 15; (1882); p. 1116 View in Reaxys O

(+-)-benzoic acid-<1-chloro-ethyl ester> Cl

Rx-ID: 5853243 View in Reaxys 145/294 Yield

Conditions & References Patent; Soc. Usines Chim. Rhone-Poulenc; DE527874; (1929); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 18; p. 796 View in Reaxys O

O OH O

Rx-ID: 36260238 View in Reaxys 146/294 Yield

Conditions & References Reaction Steps: 2 Patent; Hirai, Kunihiro; Katayama, Satoshi; Torii, Takayoshi; Nakaya, Ryotaro; Takahashi, Daisuke; US2013/267697; (2013); (A1) English View in Reaxys O

O O

Rx-ID: 673926 View in Reaxys 147/294 Yield

Conditions & References Adams; Ulich; Journal of the American Chemical Society; vol. 42; (1920); p. 607 View in Reaxys

Rx-ID: 758040 View in Reaxys 148/294 Yield

Conditions & References (1.2-1.5 Mol der Verb. 2) - beim Behandeln von Natriumbenzoat

76/118

2016-07-02 05:35:12

Adams; Ulich; Journal of the American Chemical Society; vol. 42; (1920); p. 607 View in Reaxys Adams; Wirth; French; Journal of the American Chemical Society; vol. 40; (1918); p. 424 View in Reaxys

O O

Rx-ID: 857441 View in Reaxys 149/294 Yield

Conditions & References Lichtausschluss Kharasch; Brown; Journal of the American Chemical Society; vol. 64; (1942); p. 329,332 View in Reaxys

O N

Cl –

N+

Rx-ID: 2628594 View in Reaxys 150/294 Yield

Conditions & References in dichloromethane, T= 25 °C , Rate constant, Equilibrium constant Dadali, V. A.; Zubareva, T. M.; Litvinenko, L. M.; Simanenko, Yu. S.; Journal of Organic Chemistry USSR (English Translation); vol. 20; nb. 8; (1984); p. 1543 - 1551; Zhurnal Organicheskoi Khimii; vol. 20; nb. 8; (1984); p. 1695 1704 View in Reaxys O

Cl O

Rx-ID: 26439783 View in Reaxys 151/294 Yield

Conditions & References vol. C: MVol.D3; 2.2.8.8, page 101 - 102 View in Reaxys Hardy, E. E.; in: Kirk-Othmer, Encyclopedia of Chemical Technology, 2. Aufl., Erg.-Bd., New York-London-SydneyToronto 1971, S. 674/83 ; (from Gmelin) View in Reaxys

H N O

O O

Cl Cl

PCl Cl Cl

N Cl

Rx-ID: 7056601 View in Reaxys 152/294 Yield

Conditions & References T= 110 °C , p= 60Torr Lossen; Justus Liebigs Annalen der Chemie; vol. 252; (1889); p. 221,222 View in Reaxys

77/118

2016-07-02 05:35:12

(v5)

(v4)

O Pt P

(v4)

(v5)

P (v4) Pt SP-4

(v4) (v4)

Rx-ID: 35274474 View in Reaxys 153/294 Yield

Conditions & References in benzene-d6, T= 35 °C , Glovebox, Equilibrium constant Kuniyasu, Hitoshi; Sanagawa, Atsushi; Nakane, Daisuke; Iwasaki, Takanori; Kambe, Nobuaki; Bobuatong, Karan; Lu, Yunpeng; Ehara, Masahiro; Organometallics; vol. 32; nb. 6; (2013); p. 2026 - 2032 View in Reaxys

(v4)

Pt SP-4

(v4)

P (v4) Pt SP-4

(v4) (v4)

Rx-ID: 35274490 View in Reaxys 154/294 Yield

Conditions & References in benzene-d6, Time= 24h, T= 35 °C , Glovebox, Equilibrium constant, Activation energy, Reagent/catalyst, Solvent, Temperature Kuniyasu, Hitoshi; Sanagawa, Atsushi; Nakane, Daisuke; Iwasaki, Takanori; Kambe, Nobuaki; Bobuatong, Karan; Lu, Yunpeng; Ehara, Masahiro; Organometallics; vol. 32; nb. 6; (2013); p. 2026 - 2032 View in Reaxys O

O–

K+ O

Rx-ID: 2955094 View in Reaxys 155/294 Yield

Conditions & References With antimony(V) pentachloride, Time= 0.566667h, T= 60 °C , other Lewis acids as catalysts; other time; other temperature; other aromatic acids as educts. Object of study: the influence of Lewis acid(s) used on the conversion, selectivity., Mechanism Freidlin, E. G.; Shcherbik, L. K.; Palei, B. A.; Krasil'nikova, G. S.; Shadrova, N. N.; Journal of Organic Chemistry USSR (English Translation); (1980); p. 915 - 918; Zhurnal Organicheskoi Khimii; vol. 16; nb. 5; (1980); p. 1040 1043 View in Reaxys

O O

O Cl

paraffin

indigo yellow-3G Cl

N O

Rx-ID: 5735491 View in Reaxys 156/294 Yield

Conditions & References T= 315 °C Hope; Richter; Journal of the Chemical Society; (1932); p. 2784,2785 View in Reaxys

78/118

2016-07-02 05:35:12

de Diesbach et al.; Helvetica Chimica Acta; vol. 17; (1934); p. 113,122; Helvetica Chimica Acta; vol. 23; (1940); p. 469,481 View in Reaxys

Rx-ID: 597626 View in Reaxys 157/294 Yield

Conditions & References With tetrachloromethane Goldschmidt; Endres; Dirsch; Chemische Berichte; vol. 58; (1925); p. 576 View in Reaxys Goldsmith; Endres; Dirsch; Chemische Berichte; vol. 58; (1925); p. 577 View in Reaxys

sodium naphthalene sulfonate-(2) Cl

naphthalene-sulfonic acid-(2)-chloride

Rx-ID: 6216829 View in Reaxys 158/294 Yield

Conditions & References T= 200 °C Patent; I.G. Farbenind.; US2016784; (1932) View in Reaxys Patent; I.G. Farbenind.; FR739290; (1932) View in Reaxys O

O S

Rx-ID: 7448412 View in Reaxys 159/294 Yield

Conditions & References Douglass; Johnson; Journal of the American Chemical Society; vol. 60; (1938); p. 1488 View in Reaxys

oxygen Cl

sulfur

sulfur dioxide

Rx-ID: 7458162 View in Reaxys 160/294 Yield

Conditions & References T= 100 - 120 °C Staudinger; Siegwart; Helvetica Chimica Acta; vol. 3; (1920); p. 838 View in Reaxys

Cl O

O Cl

Rx-ID: 9668136 View in Reaxys 161/294 Yield

Conditions & References in dichloromethane, Kinetics Showalter, Brett M.; Toscane, John P.; Journal of Physical Organic Chemistry; vol. 17; nb. 9; (2004); p. 743 - 748 View in Reaxys

79/118

2016-07-02 05:35:12

Rx-ID: 757842 View in Reaxys 162/294 Yield

Conditions & References Anschuetz; Justus Liebigs Annalen der Chemie; vol. 439; (1924); p. 274 View in Reaxys T= 90 °C Anschuetz; Justus Liebigs Annalen der Chemie; vol. 439; (1924); p. 274 View in Reaxys T= 90 °C Anschuetz; Justus Liebigs Annalen der Chemie; vol. 439; (1924); p. 274 View in Reaxys

Cl Cl

PCl Cl

O O

O Cl

O O

Rx-ID: 5673593 View in Reaxys 163/294 Yield

Conditions & References T= 130 °C , im Rohr, <O.O-dibenzoyl-d-tartaric acid >-anhydride Zetzsche; Hubacher; Helvetica Chimica Acta; vol. 9; (1926); p. 293 View in Reaxys Vallee; Annales de Chimie (Cachan, France); vol. <8> 15; (1908); p. 378 View in Reaxys O

Cl HO

Rx-ID: 5820031 View in Reaxys 164/294 Yield

Conditions & References T= 130 - 200 °C Patent; Imp. Chem. Ind.; US1851832; (1928) View in Reaxys Patent; Imp. Chem. Ind.; GB310909; (1928) View in Reaxys O

NOCl Cl

Rx-ID: 5820037 View in Reaxys 165/294 Yield

Conditions & References T= 150 - 200 °C Perrot; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 206; (1938); p. 1576 View in Reaxys

Cl Cl

steam Cl

Rx-ID: 5820043 View in Reaxys 166/294

80/118

2016-07-02 05:35:12

Yield

Conditions & References T= 240 °C , Leiten ueber Zinnphosphat Abkin; Medwedew; ; vol. 11; nb. 1; (1934); p. 30; Chem. Zentralbl.; vol. 106; nb. I; (1935); p. 2801 View in Reaxys

N N

N Cl

Rx-ID: 110559 View in Reaxys 167/294 Yield

Conditions & References T= 100 °C , bei der Einwirkung auf Natriumbenzoat Senier; Chemische Berichte; vol. 19; (1886); p. 311 View in Reaxys O

Cl O Cl

Rx-ID: 375904 View in Reaxys 168/294 Yield

Conditions & References T= 190 - 200 °C Klages; Knoevenagel; Chemische Berichte; vol. 26; (1893); p. 447 View in Reaxys Cl

Cl O

Cl N

Cl Cl

Rx-ID: 492261 View in Reaxys 169/294 Yield

Conditions & References T= 150 - 200 °C Chattaway; Orton; Journal of the Chemical Society; vol. 75; (1899); p. 1050; Journal of the Chemical Society; vol. 79; (1901); p. 277 View in Reaxys

O Cl O

Rx-ID: 505037 View in Reaxys 170/294 Yield

Conditions & References T= 200 °C Klages; Tetzner; Chemische Berichte; vol. 35; (1902); p. 3970 View in Reaxys

Cl Cl Cl

Cl O

Rx-ID: 666234 View in Reaxys 171/294

81/118

2016-07-02 05:35:12

Yield

Conditions & References T= 100 - 120 °C Rabcewicz-Zubkowski; Roczniki Chemii; vol. 9; p. 526,527; Chem. Zentralbl.; vol. 100; nb. II; (1929); p. 2766 View in Reaxys Rabcewicz-Zubkowski; Roczniki Chemii; vol. 9; p. 526; Chem. Zentralbl.; vol. 100; nb. II; (1929); p. 2766 View in Reaxys O

Rx-ID: 689590 View in Reaxys 172/294 Yield

Conditions & References T= 140 °C Biehringer; Borsum; Chemische Berichte; vol. 39; (1906); p. 3351 View in Reaxys

Cl O

Cl Cl

Rx-ID: 758052 View in Reaxys 173/294 Yield

Conditions & References T= 95 - 105 °C , und Destillieren des oeligen Reaktionsprodukts Kraft; Alekseew; Zhurnal Obshchei Khimii; vol. 2; (1932); p. 726,728; Chem. Zentralbl.; vol. 104; nb. II; (1933); p. 1666 View in Reaxys NH

O O

N H

H N

H Cl

NH 2

Rx-ID: 1344552 View in Reaxys 174/294 Yield

Conditions & References in acetic acid, Equilibrium constant Janssen,M.J.; Spoelstra,J.; Zeitschrift fuer Chemie (Stuttgart, Germany); vol. 10; (1970); p. 391 - 392 View in Reaxys O N E

H N

O Cl

H N S

Rx-ID: 1344569 View in Reaxys 175/294 Yield

Conditions & References in acetic acid, Equilibrium constant Janssen,M.J.; Spoelstra,J.; Zeitschrift fuer Chemie (Stuttgart, Germany); vol. 10; (1970); p. 391 - 392 View in Reaxys NH N

O S

NH 2

Rx-ID: 1344694 View in Reaxys 176/294 Yield

Conditions & References in acetic acid, Equilibrium constant

82/118

2016-07-02 05:35:12

Janssen,M.J.; Spoelstra,J.; Zeitschrift fuer Chemie (Stuttgart, Germany); vol. 10; (1970); p. 391 - 392 View in Reaxys

O O

H N

H Cl

N S

Rx-ID: 1344792 View in Reaxys 177/294 Yield

Conditions & References in acetic acid, Equilibrium constant Janssen,M.J.; Spoelstra,J.; Zeitschrift fuer Chemie (Stuttgart, Germany); vol. 10; (1970); p. 391 - 392 View in Reaxys O

N Cl –

N+

Rx-ID: 1345524 View in Reaxys 178/294 Yield

Conditions & References in acetic acid, Equilibrium constant Janssen,M.J.; Spoelstra,J.; Zeitschrift fuer Chemie (Stuttgart, Germany); vol. 10; (1970); p. 391 - 392 View in Reaxys Cl

Cl Cl

Rx-ID: 2678991 View in Reaxys 179/294 Yield

Conditions & References T= 500 - 600 °C , Heating, other temp., Product distribution Gisch, John F.; Landgrebe, John A.; Journal of Organic Chemistry; vol. 50; nb. 12; (1985); p. 2050 - 2054 View in Reaxys

Rx-ID: 5820028 View in Reaxys 180/294 Yield

Conditions & References T= 100 °C Acree; American Chemical Journal; vol. 50; (1913); p. 393 View in Reaxys

sodium-<4-nitro-benzene sulfonate-(1)>

N H

O Cl

Rx-ID: 5820052 View in Reaxys 181/294 Yield

Conditions & References T= 180 °C

83/118

2016-07-02 05:35:12

Barber; Journal of the Chemical Society; (1943); p. 101,103 View in Reaxys Cl

methyl dibenzoate

Rx-ID: 6215867 View in Reaxys 182/294 Yield

Conditions & References T= 105 °C Kraft; Alekseew; Zhurnal Obshchei Khimii; vol. 2; (1932); p. 726,728; Chem. Zentralbl.; vol. 104; nb. II; (1933); p. 1666 View in Reaxys

disulfur dichloride

sulfur

H Cl

Rx-ID: 6220073 View in Reaxys 183/294 Yield

Conditions & References T= 150 °C Loth; Michaelis; Chemische Berichte; vol. 27; (1894); p. 2548 View in Reaxys Cl

O Cl

PCl Cl

Rx-ID: 6680993 View in Reaxys 184/294 Yield

Conditions & References T= 160 - 180 °C Authenrieth; Muehlinghaus; Chemische Berichte; vol. 40; (1907); p. 748 View in Reaxys O

glass Cl

SiF4

NaCl

Rx-ID: 7457822 View in Reaxys 185/294 Yield

Conditions & References T= 160 °C Swarts; Chem. Zentralbl.; vol. 74; nb. I; (1903); p. 14 View in Reaxys Cl

H N

tetrahydroquinone Cl

Rx-ID: 8288554 View in Reaxys 186/294 Yield

Conditions & References p= 10 - 14Torr , beim Destillieren v.Braun; Steinsorff; Chemische Berichte; vol. 37; (1904); p. 4725 View in Reaxys

84/118

2016-07-02 05:35:12

Rx-ID: 642056 View in Reaxys 187/294 Yield

O O

Rx-ID: 651901 View in Reaxys 188/294 Yield

Conditions & References T= 105 °C Kraft; Alekseew; Zhurnal Obshchei Khimii; vol. 2; (1932); p. 726,728; Chem. Zentralbl.; vol. 104; nb. II; (1933); p. 1666 View in Reaxys

H N

NH 2

Cl O

Rx-ID: 666233 View in Reaxys 189/294 Yield

Conditions & References T= 80 - 90 °C Rabcewicz-Zubkowski; Roczniki Chemii; vol. 9; p. 526,527; Chem. Zentralbl.; vol. 100; nb. II; (1929); p. 2766 View in Reaxys Rabcewicz-Zubkowski; Roczniki Chemii; vol. 9; p. 526; Chem. Zentralbl.; vol. 100; nb. II; (1929); p. 2766 View in Reaxys O

Cl HO

Cl Cl

O Cl

Rx-ID: 666238 View in Reaxys 190/294 Yield

Conditions & References T= 140 - 170 °C Patent; Turnbull; US1793917; (1926) View in Reaxys

Rx-ID: 5820049 View in Reaxys 191/294 Yield

Conditions & References T= 40 °C Acree; American Chemical Journal; vol. 50; (1913); p. 393 View in Reaxys

S O

Cl HO

Rx-ID: 5820053 View in Reaxys 192/294

85/118

2016-07-02 05:35:12

Yield

Conditions & References T= 180 °C Barger; Journal of the Chemical Society; vol. 93; (1908); p. 565; Chemische Berichte; vol. 42; (1909); p. 763 View in Reaxys

nickel-powder

air

Rx-ID: 5958077 View in Reaxys 193/294 Yield

Conditions & References T= 160 °C Korczynski; Reinholz; Schmidt; Roczniki Chemii; vol. 9; (1929); p. 731,738; Chem. Zentralbl.; vol. 101; nb. I; (1930); p. 2075 View in Reaxys

Cl O

H 2N

symm. dibenzoylurea

carbon dioxide and ammonium chloride and hydrogen chloride Rx-ID: 6731551 View in Reaxys 194/294

Yield

Conditions & References T= 160 - 170 °C Schmidt,E.; Journal fuer Praktische Chemie (Leipzig); vol. <2>5; (1872); p. 63 View in Reaxys O Cl

PCl Cl

Rx-ID: 7443732 View in Reaxys 195/294 Yield

Conditions & References T= 140 °C Michael; American Chemical Journal; vol. 9; (1887); p. 215; Journal fuer Praktische Chemie (Leipzig); vol. <2>35; (1887); p. 96 View in Reaxys

Cl Cl

Rx-ID: 7446032 View in Reaxys 196/294 Yield

Conditions & References T= 150 - 170 °C Seelig; Journal fuer Praktische Chemie (Leipzig); vol. <2> 39; (1889); p. 175 View in Reaxys O

O N

Rx-ID: 7917260 View in Reaxys 197/294

86/118

2016-07-02 05:35:12

Yield

Conditions & References T= 250 - 270 °C Chapman; Journal of the Chemical Society; vol. 127; (1925); p. 2819 View in Reaxys

O Cl

N Cl

O O

Rx-ID: 340387 View in Reaxys 198/294 Yield

Conditions & References T= 200 °C Veres; Horak; Collection of Czechoslovak Chemical Communications; vol. 20; (1955); p. 371,373 View in Reaxys

NH 2

Rx-ID: 475496 View in Reaxys 199/294 Yield

Conditions & References T= 140 °C van Peski; Recueil des Travaux Chimiques des Pays-Bas; vol. 41; (1922); p. 698 View in Reaxys

N+

O Cl –

Cl O

O O

Rx-ID: 628848 View in Reaxys 200/294 Yield

Conditions & References T= 180 °C Knorr; Rabe; Justus Liebigs Annalen der Chemie; vol. 293; (1896); p. 42 View in Reaxys

Na + O–

chlorosulfonate sodium HO

Rx-ID: 5820036 View in Reaxys 201/294 Yield

Conditions & References Verb. 1 = 1 Mol Patent; Bad. Anilin- u. Sodaf.; DE146690 View in Reaxys Heumann; Koechlin; Chemische Berichte; vol. 15; (1882); p. 1116 View in Reaxys Verb. 1 = 1 Mol

87/118

2016-07-02 05:35:12

BASF; Chem. Zentralbl.; vol. 75; nb. I; (1904); p. 65 View in Reaxys O

sulfur chloride HO

Rx-ID: 5820044 View in Reaxys 202/294 Yield

Conditions & References bei der Einwirkung auf Natriumbenzoat Heintz; Jahresbericht ueber die Fortschritte der Chemie und Verwandter Theile Anderer Wissenschaften; (1856); p. 464 View in Reaxys Heintz; ; vol. 98; (1856); p. 473 View in Reaxys Cahours; Justus Liebigs Annalen der Chemie; vol. 106; (1858); p. 299 View in Reaxys O

O O

Cl O

Cl Cl

Rx-ID: 7450044 View in Reaxys 203/294 Yield

Conditions & References T= 200 °C Seelig; Journal fuer Praktische Chemie (Leipzig); vol. <2> 39; (1889); p. 175 View in Reaxys O

O HO

Rx-ID: 7920421 View in Reaxys 204/294 Yield

Conditions & References T= 140 - 150 °C Greene; Bulletin de la Societe Chimique de France; vol. <2> 33; (1880); p. 425 View in Reaxys Loir; Bulletin de la Societe Chimique de France; vol. <2> 32; (1879); p. 168 View in Reaxys O

H 2N O

N H

Rx-ID: 576864 View in Reaxys 205/294 Yield

Conditions & References T= 140 °C Titherley; Holden; Journal of the Chemical Society; vol. 101; (1912); p. 1886 View in Reaxys

H 2N

N Cl

Rx-ID: 666266 View in Reaxys 206/294 Yield

Conditions & References T= 130 - 140 °C , reagiert aehnlich mit anderen Saeureamiden

88/118

2016-07-02 05:35:12

Titherley; Holden; Journal of the Chemical Society; vol. 101; (1912); p. 1886 View in Reaxys O Cl

O N H

H 2N

Rx-ID: 666267 View in Reaxys 207/294 Yield

Conditions & References T= 140 °C Titherley; Holden; Journal of the Chemical Society; vol. 101; (1912); p. 1886 View in Reaxys

H 2N

Cl O

Cl –

(v4)

N HH

Rx-ID: 5673594 View in Reaxys 208/294 Yield

Conditions & References T= 160 - 170 °C , im geschlossenen Rohr Schmidt,E.; Journal fuer Praktische Chemie (Leipzig); vol. <2>5; (1872); p. 63 View in Reaxys

Cl Al

Cl O

Rx-ID: 6712153 View in Reaxys 209/294 Yield

Conditions & References T= -6 °C Reijnhart; Recueil des Travaux Chimiques des Pays-Bas; vol. 46; (1927); p. 71 View in Reaxys T= 55 °C Reijnhart; Recueil des Travaux Chimiques des Pays-Bas; vol. 46; (1927); p. 71 View in Reaxys

O O

Rx-ID: 293964 View in Reaxys 210/294 Yield

Conditions & References bei der Destillation Zinin; Justus Liebigs Annalen der Chemie; vol. 119; (1861); p. 180; Justus Liebigs Annalen der Chemie; vol. 126; (1863); p. 218 View in Reaxys

O O

S Cl

Rx-ID: 730164 View in Reaxys 211/294 Yield

Conditions & References bei der Einwirkung auf 1 Mol Natriumbenzoat

89/118

2016-07-02 05:35:12

Patent; Chem. Fabr. von Heyden; DE123052 View in Reaxys Chem. Fabr. von Heyden; Chem. Zentralbl.; vol. 72; nb. II; (1901); p. 518 View in Reaxys

Rx-ID: 5820025 View in Reaxys 212/294 Yield

Conditions & References Gautier; Annales de Chimie (Cachan, France); vol. <6> 14; (1888); p. 362 View in Reaxys Woehler; Liebig; Justus Liebigs Annalen der Chemie; vol. 3; (1832); p. 262 View in Reaxys

PCl Cl

Rx-ID: 5820030 View in Reaxys 213/294 Yield

Conditions & References Cahours; Annales de Chimie (Cachan, France); vol. <3> 23; (1848); p. 345; Justus Liebigs Annalen der Chemie; vol. 70; (1849); p. 44 View in Reaxys Cahours; Justus Liebigs Annalen der Chemie; vol. 70; (1849); p. 45; Annales de Chimie (Cachan, France); vol. <3> 23; (1848); p. 347 View in Reaxys

P Cl

Rx-ID: 5820032 View in Reaxys 214/294 Yield

Conditions & References bei der Einwirkung auf hoechsten 3 Mol Natriumbenzoat Gerhardt; Annales de Chimie (Cachan, France); vol. <3> 37; (1853); p. 300; Justus Liebigs Annalen der Chemie; vol. 87; (1853); p. 73 View in Reaxys Gerhardt; Justus Liebigs Annalen der Chemie; vol. 87; (1853); p. 81 View in Reaxys

CdO Cl

Rx-ID: 5820033 View in Reaxys 215/294 Yield

Conditions & References Davies; Dick; Journal of the Chemical Society; (1932); p. 2808 View in Reaxys O

O O

S2cl2

Rx-ID: 5820038 View in Reaxys 216/294 Yield

Conditions & References Denham; Woodhouse; Journal of the Chemical Society; vol. 103; (1913); p. 1866 View in Reaxys

90/118

2016-07-02 05:35:12

CS2

sulfur chloride HO

Rx-ID: 5820045 View in Reaxys 217/294 Yield

Conditions & References unter Kuehlung Cahours; Justus Liebigs Annalen der Chemie; vol. 106; (1858); p. 302 View in Reaxys

ZnO Cl

Rx-ID: 5820046 View in Reaxys 218/294 Yield

Conditions & References Davies; Dick; Journal of the Chemical Society; (1932); p. 2808 View in Reaxys O Cl

HO O

N H

PCl Cl Cl

compound C9H6ONCl

compound C9H5ONCl2 Rx-ID: 6727443 View in Reaxys 219/294

Yield

Conditions & References Schwanert; Justus Liebigs Annalen der Chemie; vol. 112; (1859); p. 66 View in Reaxys Ruegheimer; Chemische Berichte; vol. 19; (1886); p. 1169 View in Reaxys O

O O

N H Cl

Rx-ID: 371292 View in Reaxys 220/294 Yield

Conditions & References beim Aufbewahren Beckmann; Sandel; Justus Liebigs Annalen der Chemie; vol. 296; (1897); p. 293 View in Reaxys O

Cl O

Rx-ID: 371293 View in Reaxys 221/294 Yield

Conditions & References zerfaellt beim Erhitzen ueber den Schmelzpunkt Titherley; Worrall; Journal of the Chemical Society; vol. 97; (1910); p. 840 View in Reaxys

91/118

2016-07-02 05:35:12

O Cl

Rx-ID: 414229 View in Reaxys 222/294 Yield

Conditions & References beim Destillieren unter vermindertem Druck Klages; Tetzner; Chemische Berichte; vol. 35; (1902); p. 3970 View in Reaxys

O Cl E

Rx-ID: 504734 View in Reaxys 223/294 Yield

Conditions & References beim Destillieren unter vermindertem Druck Klages; Tetzner; Chemische Berichte; vol. 35; (1902); p. 3970 View in Reaxys O

P Cl

Rx-ID: 620937 View in Reaxys 224/294 Yield

Conditions & References Gibson; Johnson; Journal of the Chemical Society; (1928); p. 94,98 View in Reaxys O

Rx-ID: 846914 View in Reaxys 225/294 Yield

Conditions & References Staudinger; Chemische Berichte; vol. 41; (1908); p. 3566 View in Reaxys Giua; Gazzetta Chimica Italiana; vol. 47 I; (1917); p. 55 View in Reaxys

Cl S Cl

Rx-ID: 5673591 View in Reaxys 226/294 Yield

Conditions & References Durrans; Journal of the Chemical Society; vol. 121; (1922); p. 46 View in Reaxys

NOCl O

Rx-ID: 5690850 View in Reaxys 227/294

92/118

2016-07-02 05:35:12

Yield

Conditions & References Sonnenlicht.Irradiation Lee; Lynn; Journal of the American Pharmaceutical Association (1912-1977); vol. 21; (1932); p. 125; Chem. Zentralbl.; vol. 103; nb. I; (1932); p. 3403 View in Reaxys

S Cl

anhydropyridinesulfuric acid

Rx-ID: 5725465 View in Reaxys 228/294 Yield

Conditions & References unter Kuehlung und anschl. Zersetzen mit Benzoesaeure Wagner; Chemische Berichte; vol. 19; (1886); p. 1157 View in Reaxys Baumgarten; Chemische Berichte; vol. 60; (1927); p. 1175 Anm. 3 View in Reaxys

S Cl

anhydropyridinesulfuric acid

Rx-ID: 5725466 View in Reaxys 229/294 Yield

H 2N

nitrosyl chloride O

nitrogen Rx-ID: 5739963 View in Reaxys 230/294

Yield

Conditions & References im geschlossenen Rohr Tilden; Forster; Journal of the Chemical Society; vol. 67; (1895); p. 492 View in Reaxys O

O O

Rx-ID: 5820027 View in Reaxys 231/294 Yield

Conditions & References im Sonnenlicht Gal; Annales de Chimie (Cachan, France); vol. <3>66; (1862); p. 188,190 View in Reaxys

S O

Rx-ID: 5820029 View in Reaxys 232/294 Yield

Conditions & References Heumann; Koechlin; Chemische Berichte; vol. 16; (1883); p. 1627 View in Reaxys

93/118

2016-07-02 05:35:12

Cl Cl

iron-powder Cl

O Cl

Rx-ID: 5820050 View in Reaxys 233/294 Yield

Conditions & References Patent; McKee; DE540588; (1926); Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 17; p. 478 View in Reaxys O

Rx-ID: 6680994 View in Reaxys 234/294 Yield

Conditions & References bei kurzer Dauer der Reaktion Friedel; Crafts; Ador; Annales de Chimie (Cachan, France); vol. <6> 1; (1884); p. 516 View in Reaxys Elbs; Journal fuer Praktische Chemie (Leipzig); vol. <2> 35; (1887); p. 466 View in Reaxys Friedel; Crafts; Ador; Chemische Berichte; vol. 10; (1877); p. 1857; Annales de Chimie (Cachan, France); vol. <6> 1; (1884); p. 521 View in Reaxys

Cl Al

OH O

H 2N 2

Rx-ID: 6682226 View in Reaxys 235/294 Yield

Conditions & References Gelissen; Hermans; Chemische Berichte; vol. 58; (1925); p. 478 View in Reaxys Reijnhart; Recueil des Travaux Chimiques des Pays-Bas; vol. 46; (1927); p. 62 View in Reaxys Boeeseken; Reijnhart; Verslag van de Gewone Vergadering van de Afdeling Natuurkunde, Koninklijke Nederlandse Akademie van Wetenschappen; vol. 34; p. 1100,1101; Chem. Zentralbl.; vol. 97; nb. I; (1926); p. 2196 View in Reaxys

Rx-ID: 7443731 View in Reaxys 236/294 Yield

Conditions & References Staudinger; Anthes; Chemische Berichte; vol. 46; (1913); p. 1435 View in Reaxys N O

H N

Z N

Rx-ID: 8251949 View in Reaxys 237/294 Yield

Conditions & References Ehrlich; Sachs; Chemische Berichte; vol. 32; (1899); p. 2344 View in Reaxys

94/118

2016-07-02 05:35:12

O O

S Cl

Rx-ID: 21922 View in Reaxys 238/294 Yield

Conditions & References Ullmann; Nadai; Chemische Berichte; vol. 41; (1908); p. 1873 View in Reaxys O

O O

O Cl

Rx-ID: 61125 View in Reaxys 239/294 Yield

Conditions & References bei der Chlorierung Baumgarten; Chemische Berichte; vol. 58; (1925); p. 2021 View in Reaxys O

O O

Rx-ID: 171665 View in Reaxys 240/294 Yield

Conditions & References bei der Chlorierung Baumgarten; Chemische Berichte; vol. 58; (1925); p. 2021 View in Reaxys

Cl Cl

Rx-ID: 597294 View in Reaxys 241/294 Yield

Conditions & References Goldschmidt; Endres; Dirsch; Chemische Berichte; vol. 58; (1925); p. 576 View in Reaxys

Rx-ID: 597295 View in Reaxys 242/294 Yield

Conditions & References Musante; Fusco; Gazzetta Chimica Italiana; vol. 66; (1936); p. 639,645 View in Reaxys

Cl O

Cl HO

Rx-ID: 757801 View in Reaxys 243/294 Yield

Conditions & References Heslinga et al.; Recueil des Travaux Chimiques des Pays-Bas; vol. 76; (1957); p. 969,972 View in Reaxys

O E Cl

Rx-ID: 757811 View in Reaxys 244/294

95/118

2016-07-02 05:35:12

Yield

Conditions & References Crompton; Vanderstichele; Journal of the Chemical Society; vol. 117; (1920); p. 692 View in Reaxys Br O

O O

O Br

Rx-ID: 757813 View in Reaxys 245/294 Yield

Conditions & References Smith; Journal of the Chemical Society; (1927); p. 1101 View in Reaxys

O Cl Cl

PCl Cl

Rx-ID: 5673592 View in Reaxys 246/294 Yield

Conditions & References Michaelis; Bender; Chemische Berichte; vol. 36; (1903); p. 524 View in Reaxys

O N Cl Cl

PCl Cl

Rx-ID: 5678837 View in Reaxys 247/294 Yield

Conditions & References Wieland; Chemische Berichte; vol. 42; (1909); p. 814 View in Reaxys

Cl Fe Cl

(v3)

Rx-ID: 5820026 View in Reaxys 248/294 Yield

Conditions & References Patent; BASF; DE331696; Fortschr. Teerfarbenfabr. Verw. Industriezweige; vol. 13; p. 272 View in Reaxys

Cl O

O O

Rx-ID: 5820051 View in Reaxys 249/294 Yield

Conditions & References bei der Einwirkung auf Silberbenzoat Meyer; Justus Liebigs Annalen der Chemie; vol. 156; (1870); p. 271 Anm. View in Reaxys

96/118

2016-07-02 05:35:12

O O

Rx-ID: 5958076 View in Reaxys 250/294 Yield

Conditions & References Mosling; Justus Liebigs Annalen der Chemie; vol. 118; (1861); p. 304 View in Reaxys

nickel

air

Rx-ID: 6683394 View in Reaxys 251/294 Yield

Conditions & References Korczynski; Reinholz; Schmidt; Roczniki Chemii; vol. 9; (1929); p. 731,738; Chem. Zentralbl.; vol. 101; nb. I; (1930); p. 2075 View in Reaxys

O Cl

Rx-ID: 7443733 View in Reaxys 252/294 Yield

Conditions & References Sintenis; Justus Liebigs Annalen der Chemie; vol. 161; (1872); p. 337 View in Reaxys OH

Cl Cl

N E

PCl Cl

Rx-ID: 7445060 View in Reaxys 253/294 Yield

Conditions & References Durio; Sburlati; Gazzetta Chimica Italiana; vol. 62; (1932); p. 1035,1038 View in Reaxys O

chlorosulfur

Rx-ID: 7452025 View in Reaxys 254/294 Yield

Conditions & References Schiller; Otto; Chemische Berichte; vol. 9; (1876); p. 1635 View in Reaxys O

O O

O HO

Rx-ID: 7919313 View in Reaxys 255/294 Yield

Conditions & References Behal; Bulletin de la Societe Chimique de France; vol. <3> 23; (1900); p. 81; Annales de Chimie (Cachan, France); vol. <7> 19; (1900); p. 287 View in Reaxys Greene; Bulletin de la Societe Chimique de France; vol. <2> 33; (1880); p. 425 View in Reaxys Loir; Bulletin de la Societe Chimique de France; vol. <2> 32; (1879); p. 168 View in Reaxys

97/118

2016-07-02 05:35:12

S N

Rx-ID: 7919387 View in Reaxys 256/294 Yield

Conditions & References Rivier; Schneider; Helvetica Chimica Acta; vol. 3; (1920); p. 132 View in Reaxys

N+

O Cl –

pseudothiopyrine

Cl O

Rx-ID: 8285955 View in Reaxys 257/294 Yield

Conditions & References bei der Vakuumdestillation Michaelis; Pander; Chemische Berichte; vol. 37; (1904); p. 2774; Justus Liebigs Annalen der Chemie; vol. 361; (1908); p. 262 View in Reaxys

H 2N

Rx-ID: 576876 View in Reaxys 258/294 Yield

Conditions & References Titherley; Holden; Journal of the Chemical Society; vol. 101; (1912); p. 1886 View in Reaxys 1

H 2N

H Cl –

H O

H 2N Cl

(v4)

N HH

Rx-ID: 5673595 View in Reaxys 259/294 Yield

Conditions & References Titherley; Holden; Journal of the Chemical Society; vol. 101; (1912); p. 1886 View in Reaxys

P Cl

Rx-ID: 5820048 View in Reaxys 260/294 Yield

Conditions & References Backes; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 196; (1933); p. 1675 View in Reaxys

S Cl

Cl Cl

O HO

N-pyridiniumsulfonic acid Cl

Rx-ID: 6217530 View in Reaxys 261/294

98/118

2016-07-02 05:35:12

Yield

Conditions & References Baumgarten; Chemische Berichte; vol. 60; (1927); p. 1175 Anm. 3 View in Reaxys

Cl H

C O

Rx-ID: 6727587 View in Reaxys 262/294 Yield

Conditions & References Gavankar; Heble; Wheeler; Journal of the University of Bombay, Science: Physical Sciences, Mathematics, Biological Sciences and Medicine; vol. 6; (1937); p. 112; Chem. Zentralbl.; vol. 109; nb. I; (1938); p. 4610 View in Reaxys O

O Cl

O S

N O

Cl O

N O

Rx-ID: 7443735 View in Reaxys 263/294 Yield

Conditions & References Fries; Justus Liebigs Annalen der Chemie; vol. 454; (1927); p. 306 View in Reaxys

Cl Cl

O Cl

PCl Cl Cl

Rx-ID: 7445251 View in Reaxys 264/294 Yield

Conditions & References Ciamician; Silber; Chemische Berichte; vol. 24; (1891); p. 2989; Chemische Berichte; vol. 25; (1892); p. 1127 View in Reaxys Cl

Cl Cl

(v4)

Cl O

Rx-ID: 7446037 View in Reaxys 265/294 Yield

Conditions & References Straus; Berkow; Justus Liebigs Annalen der Chemie; vol. 401; (1913); p. 143 View in Reaxys

O Cl Cl

PCl Cl Cl

O Cl

trichlorophloroglucinol-trimethyl ether Cl

Rx-ID: 7458719 View in Reaxys 266/294 Yield

Conditions & References Ciamician; Silber; Chemische Berichte; vol. 24; (1891); p. 2989; Chemische Berichte; vol. 25; (1892); p. 1127 View in Reaxys

99/118

2016-07-02 05:35:12

Cl Cl

PCl Cl

Rx-ID: 7917261 View in Reaxys 267/294 Yield

Conditions & References anschliessende Behandlung mit Wasser Bergmann; Bondi; Chemische Berichte; vol. 63; (1930); p. 1158,1166; Chemische Berichte; vol. 64; (1931); p. 1455,1480 View in Reaxys Cl

H Cl

Rx-ID: 8251950 View in Reaxys 268/294 Yield

Conditions & References beim Erhitzen ueber den Schmelzpunkt Cook; Journal of the Chemical Society; (1926); p. 1285 View in Reaxys O

Cl Cl Cl

Cl O

Rx-ID: 1611804 View in Reaxys 269/294 Yield

Conditions & References

94 % Chromat., 41 % Chromat., 28 % Chromat., 7 % Chromat., 48 % Chromat.

Ambient temperature, Irradiation, Mechanism, Quantum yield Maruyama, Kazuhiro; Furuta, Hiroyuki; Otsuki, Tetsuo; Bulletin of the Chemical Society of Japan; vol. 53; nb. 8; (1980); p. 2421 - 2422 View in Reaxys

O S

Cl Al

Rx-ID: 6680995 View in Reaxys 270/294 Yield

Conditions & References Wilson; Fuller; ; vol. 14; (1922); p. 407; Chem. Zentralbl.; vol. 93; nb. III; (1922); p. 497 View in Reaxys

100/118

2016-07-02 05:35:12

O S

Rx-ID: 6680996 View in Reaxys 271/294 Yield

Conditions & References Staudinger; Chemische Berichte; vol. 41; (1908); p. 3566 View in Reaxys

O S

hydrogen chloride

H 2N

benziminoisothiobenzamide

Rx-ID: 6726334 View in Reaxys 272/294 Yield

Conditions & References Ishikawa; Scientific Papers of the Institute of Physical and Chemical Research (Japan); vol. 7; p. 296; Chem. Zentralbl.; vol. 99; nb. I; (1928); p. 1765 View in Reaxys O Cl

PCl Cl

E N

H N

O H 2N

Rx-ID: 7446148 View in Reaxys 273/294 Yield

Conditions & References Beckmann; Koester; Justus Liebigs Annalen der Chemie; vol. 274; (1893); p. 16 View in Reaxys Cl

(v4)

Rx-ID: 8255581 View in Reaxys 274/294 Yield

Conditions & References α.ε-dichloro-α.ε-diphenyl-α.γ-pentadiene Straus; Justus Liebigs Annalen der Chemie; vol. 393; (1912); p. 239 View in Reaxys O Cl

Rx-ID: 5820024 View in Reaxys 275/294 Yield 100%

Conditions & References 2 : Synthesis of benzoyl chloride Example 2 Synthesis of benzoyl chloride To 9.30 g (0.055 mole) of 2-chloro-1,3-dimethylimidazolinium chloride, 50.1 g of toluene was added, and successively 6.11 g (0.05 mole) of benzoic acid was added. The mixture was reacted at 110° C. for 7 hours. The reaction mass was analyzed by gas chromatography and liquid chromatography. The conversion ratio of benzoic acid was 100percent and the yield of benzoyl chloride was 100percent. Patent; Mitsui Toatsu Chemicals, Inc.; US5750779; (1998); (A1) English View in Reaxys

101/118

2016-07-02 05:35:12

100%

83 :A similar photoreaction with 380 mg (2 mmol) of cyclopropyl(4-isopropyl-phenyl) methanone (from Example 82) in 3.8 ml of chlorobenzene with 0.35 ml (3 mmol) of tert-butyl hypochlorite gave the benzylic chloride without preceding purification by crystallization with a GC purity of 91 area percent in 100percent yield (wt./wt.). Patent; SANOFI-AVENTIS DEUTSCHLAND GMBH; US2007/161814; (2007); (A1) English View in Reaxys

99%

14.c : c Prepared analogously to Example 4c) from (R,S)-3-amino-α-[(diphenylacetyl)amino]-N-[[(4-phenylmethoxy)phenyl]methyl]-benzeneacetamide, ammonium rhodanide and benzoylchloride in a yield of 99percent of theory. Colourless crystals. IR (KBr): 1637.5 (broad, amide-CO) cm-1 Patent; Dr. Karl Thomae GmbH; US5962530; (1999); (A1) English View in Reaxys

98%

16.c : c Prepared analogously to Example 4c) from (R,S)-3-amino-α-[(diphenylacetyl)amino]-N-methyl-N-[[(4-phenylmethoxy)phenyl]methyl]-benzeneacetamide, ammonium rhodanide and benzoylchloride in a yield of 98percent of theory. Colourless crystals. IR (KBr): 1643.3 (broad, amide-CO) cm-1 Patent; Dr. Karl Thomae GmbH; US5962530; (1999); (A1) English View in Reaxys

97%

11.c : c Prepared analogously to Example 4c) from (R,S)-3-amino-α-[(diphenylacetyl)amino]-N-(phenylmethyl)-benzeneacetamide, ammonium rhodanide and benzoylchloride in a yield of 97percent of theory. Colourless crystals. IR (KBr): 1641.3 (broad, amide-CO) cm-1 Patent; Dr. Karl Thomae GmbH; US5962530; (1999); (A1) English View in Reaxys

97%

83 :A similar photoreaction with 380 mg (2 mmol) of cyclopropyl(4-isopropyl-phenyl) methanone (from Example 82) in 3.8 ml of benzotrifluoride (α,α,α-trifluorotoluene) with 0.35 ml (3 mmol) of tert-butyl hypochlorite gave the benzylic chloride without preceding purification by crystallization with a GC purity of 88 area percent in 97percent yield (wt./ wt.). Patent; SANOFI-AVENTIS DEUTSCHLAND GMBH; US2007/161814; (2007); (A1) English View in Reaxys

93%

a : EXAMPLE In a fractional vacuum distillation, 1,336 g of pure benzoyl chloride are obtained (yield 93percent, relative to benzyl benzoate employed). 536 g remain as the residue. Patent; Bayer Aktiengesellschaft; US4430181; (1984); (A1) English View in Reaxys

92%

17.c : c Prepared analogously to Example 4c) from (R,S)-3-amino-N-[[4-(aminocarbonylaminomethyl)phenyl]methyl]-α-[(diphenylacetyl)amino]-N-methyl-benzeneacetamide, ammonium rhodanide and benzoylchloride in a yield of 92percent of theory. Colourless crystals. IR (KBr): 1647.1 (broad, amide-CO) cm-1 Patent; Dr. Karl Thomae GmbH; US5962530; (1999); (A1) English View in Reaxys

91.9%

28 : Synthesis of n-benzoyl chloride EXAMPLE 28 Synthesis of n-benzoyl chloride

102/118

2016-07-02 05:35:12

To a reaction vessel, 0.566 g (4.636 m mol) of benzoic acid and 3.34 g of 21.01 wt percent DMFC solution in acetonitrile (0.707 g, 4.636 m mol as DMFC) were charged and reacted at room temperature for 3 hours in a nitrogen atmosphere. After finishing the reaction, GC analysis of the reaction mixture revealed that the yield of benzoyl chloride was 91.9percent and the yield of benzoyl fluoride was 8.0percent. Patent; Mitsui Chemicals, Inc.; US6329529; (2001); (B1) English View in Reaxys 90%

11 : EXAMPLE 11 The ethereal diazomethane solution was obtained using a standard procedure by adding a solution of N-methyl-Nnitroso toluenesulphonamide (45.0 g.) in ether (300 ml.) dropwise to a stirred solution of potassium hydroxide (12.9 g.) in water (21 ml.), maintaining the reaction temperature at 50°-55° C., and the addition rate to balance the loss of ethereal diazomethane by distillation. [The starting benzoyl chloride was obtained in 90percent yield from (2-chloro-3,4-bis(benzyloxy)benzoic acid by reaction with thionyl chloride in a conventional manner and had m.p. 124°-126° C. The 2-chloro-3,4-bis(benzyloxy)benzoic acid was itself obtained in 80percent yield as a solid, m.p. 159°-162° C., by oxidation of 2-chloro-3,4-bis(benzoyloxy)benzaldehyde (itself described by Kaiser et alia in J. Medicinal Chemistry 1974, 17, 1071) with chromium trioxide in sulphuric acid solution (Jones reagent)]. A mixture of 2-bromo-3',4'-bis(benzyloxy)-2-chloroacetophenone (2.95 g.) and N-[2-(benzylamino)ethyl]-2-phenylacetamide (3.7 g.) in dioxan (20 ml.) was stirred at room temperature for 3 hours. The reaction mixture was diluted with dry ether (200 ml.) and the precipitate, N-[2-(benzylamino)ethyl]-2-phenylacetamide hydrobromide, was separated by filtration. The filtrate was washed with water (3*50 ml.) and then brine (100 ml.) dried (MgSO4), filtered, and a fresh solution of hydrogen bromide in ether added until the pH was just acid. Patent; Imperial Chemical Industries Limited; US4423070; (1983); (A1) English View in Reaxys

78%

8.c : c Prepared analogously to Example 4c) from (R,S)-3-amino-N-[[4-(aminocarbonylaminomethyl)phenyl]methyl]-α-[(diphenylacetyl)amino]-benzeneacetamide, ammonium rhodanide and benzoylchloride in a yield of 78percent of theory. Colourless, amorphous substance. IR (KBr): 1635.5 (broad, amide-CO) cm-1 ESI-MS: (M+H)+ =685 Patent; Dr. Karl Thomae GmbH; US5962530; (1999); (A1) English View in Reaxys Oishi,T. et al.; Chemical and Pharmaceutical Bulletin; vol. 19; (1971); p. 1871 - 1875 View in Reaxys Huisgen,R. et al.; Chemische Berichte; vol. 94; (1961); p. 1555 - 1562 View in Reaxys Lee,K.H.; Tetrahedron; vol. 24; (1968); p. 4793 - 4803 View in Reaxys Venkataraman,K.; Wagle,D.R.; Tetrahedron Letters; (1979); p. 3037 - 3040 View in Reaxys Bryukhova,E.V. et al.; Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation); vol. 21; (1972); p. 558 - 560; Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya; vol. 21; (1972); p. 599 - 601 View in Reaxys Patent; Hoechst; DE2240883; (1972); ; vol. 80; nb. 133056 View in Reaxys Staab et al.; Justus Liebigs Annalen der Chemie; vol. 694; (1966); p. 78,85 View in Reaxys Seyferth; Shih; Journal of the American Chemical Society; vol. 95; (1973); p. 8464 View in Reaxys Dubchenko; Kovalenko; J. Appl. Chem. USSR (Engl. Transl.); vol. 41; (1968); p. 2568,2422 View in Reaxys Gross; Gloede; Chemische Berichte; vol. 96; (1963); p. 1387,1391 View in Reaxys Eilingsfeld et al.; Angewandte Chemie; vol. 72; (1960); p. 836,837 View in Reaxys

103/118

2016-07-02 05:35:12

Zwanenburg et al.; Tetrahedron Letters; (1970); p. 4683,4685 View in Reaxys Hope; Wiles; Journal of the Chemical Society; (1964); p. 5837 View in Reaxys Dubchenko; Kovalenko; J. Appl. Chem. USSR (Engl. Transl.); vol. 41; (1968); p. 2048,1925 View in Reaxys Schmidt; Pichl; Chemische Berichte; vol. 98; (1965); p. 1003 View in Reaxys Lee; Journal of the American Chemical Society; vol. 88; (1966); p. 3440 View in Reaxys Inone et al.; Chemistry Letters; (1972); p. 207 View in Reaxys Dubchenko; J. Appl. Chem. USSR (Engl. Transl.); vol. 46; (1973); p. 1822,1933,1936 View in Reaxys Patent; Bayer A.-G.; GB942621; (1960); ; vol. 60; nb. 10607b; (1964) View in Reaxys Braden; Hollstein; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 12; (1976); p. 507,512 View in Reaxys Takata et al.; Kogyo Kagaku Zasshi; vol. 72; (1969); p. 2502; ; vol. 72; nb. 78614; (1970) View in Reaxys Patent; E.I. du Pont de Nemours and Co.; US3681453; (1969); ; vol. 77; nb. 114074 View in Reaxys Patent; Hoechst AG; DE1954793; (1971); ; vol. 75; nb. 19988 View in Reaxys Patent; Argus Chemical Corp.; US3691217; (1970); ; vol. 77; nb. 151700 View in Reaxys Patent; Union Carbide Corp.; DE1931074; (1970); ; vol. 72; nb. 78472 View in Reaxys Nakano et al.; Journal of the Chemical Society, Chemical Communications; (1977); p. 808 View in Reaxys Brook et al.; Canadian Journal of Chemistry; vol. 49; (1971); p. 133 View in Reaxys Patent; Kirch; US3686301; (1969); ; vol. 77; nb. 126250 View in Reaxys Matsuda et al.; Hokkaido Daigaku Kogakubu Kenkyu Hokoku; vol. 87; (1978); p. 151,152; ; vol. 90; nb. 6055b View in Reaxys Matsuda et al.; Hokkaido Daigaku Kogakubu Kenkyu Hokoku; vol. 95; (1979); p. 87,88; ; vol. 92; nb. 76059 View in Reaxys Dubchenko et al.; J. Appl. Chem. USSR (Engl. Transl.); vol. 45; (1972); p. 1162,1207 View in Reaxys Arai; Nippon Kagaku Zasshi; vol. 81; (1960); p. 1450; ; vol. 56; nb. 2370; (1962) View in Reaxys Patent; Nat.Distillers Chem.; NL6614185; (1967); ; vol. 67; nb. 64066 View in Reaxys Hope; Wiles; Journal of the Chemical Society; (1965); p. 5386,5390 View in Reaxys Schmall; Schunack; Scientia Pharmaceutica; vol. 42; nb. 4; (1974); p. 248 - 255 View in Reaxys Dubchenko; Kovalenko; J. Appl. Chem. USSR (Engl. Transl.); vol. 43; (1970); p. 2049,2066 View in Reaxys Nakano et al.; Organic Preparations and Procedures International; vol. 10; (1978); p. 291 View in Reaxys Patent; du Pont; US3318950; (1967); ; vol. 67; nb. 43437; (1967) View in Reaxys Matsuda et al.; Nippon Kagaku Kaishi; (1974); p. 198 View in Reaxys Patent; Union Carbide; NL6604995; (1966); ; vol. 66; nb. 37663 View in Reaxys Filimonov et al.; J. Gen. Chem. USSR (Engl. Transl.); vol. 49; (1979); p. 1098,955,956,959 View in Reaxys Patent; Besnalyj et al.; SU399501; (1974); Ref. Zh., Khim.; vol. 22; nb. N177P; (1974)

104/118

2016-07-02 05:35:12

View in Reaxys Rondestvedt; Journal of Organic Chemistry; vol. 41; (1976); p. 3574,3575, 3576 View in Reaxys Patent; Yazlovitzkii et al.; SU438641; (1975); Ref. Zh., Khim.; vol. 24; nb. N147P; (1975) View in Reaxys Ol'dekop; Kalinina; J. Gen. Chem. USSR (Engl. Transl.); vol. 34; (1964); p. 3473,3515 View in Reaxys Patent; Imperial Chem.Ind.; GB987516; (1963); ; vol. 63; nb. 1743ab; (1965) View in Reaxys Ol'dekop et al.; Doklady Chemistry; vol. 139; (1961); p. 862; Doklady Akademii Nauk SSSR; vol. 139; (1961); p. 1383 View in Reaxys Henry; Tetrahedron Letters; (1968); p. 2285 View in Reaxys Mukai et al.; Tetrahedron Letters; (1968); p. 1695 View in Reaxys Schoenberg; Frese; Chemische Berichte; vol. 101; (1968); p. 694,700 View in Reaxys Sosnovsky; Rawlinson; Journal of Organic Chemistry; vol. 33; (1968); p. 2325,2328 View in Reaxys L : N-[2-[N'-(benzamido)quinoxalinyl]-]benzamide Example L N-[2-[N'-(benzamido)quinoxalinyl]-]benzamide Preparation: 1.98 mmol of benzoyl chloride (freshly distilled) are added to a solution of 1.00 mmol of diaminoquinoxaline (160 mg) in 15.0 ml of a polar aprotic solvent (preferably THF or dioxane/dried), and the mixture is refluxed for 48-72 hours. After cooling, the solvent is removed, and the residue is purified by column chromatography on silica gel using a solvent/eluent mixture of cyclohexane/ethyl acetate-->ethyl acetate/ethanol. Patent; Pluecker, Frank; Driller, Hansj?uuml;rgen; Kirschbaum, Michael; Scholz, Volker; Neunhoeffer, Hans; US2003/207886; (2003); (A1) English View in Reaxys 8 : Synthesis of N-tert-butyl Benzamide Using N-(1-chloro-2-methylprop-1-enyl)-N-methyl Aminomethylpolystyrene EXAMPLE 8 Synthesis of N-tert-butyl Benzamide Using N-(1-chloro-2-methylprop-1-enyl)-N-methyl Aminomethylpolystyrene A mixture of benzoic acid (1.00 g, 8.2 mmol) and N-(1-chloro-2-methylprop-1-enyl)-N-methyl aminomethylpolystyrene (1.55 mequiv/g, 8.00 g, 12.4 mequiv) in anhydrous acetonitrile (25 mL) was stirred at ambient temperature with no significant exotherm. Benzoyl chloride was cleanly formed over 10 minutes. 1H NMR (CD3CN): δ 8.17-8.12 (m, 2H), 7.83-7.76 (m, 1H), 7.64-7.57 (m, 2H). GC-MS m/z 140 (M+). Patent; Pharmacia Corporation; US2003/80320; (2003); (A1) English View in Reaxys and 24, characterized in that the acylating agent is chosen from: acetic anhydride, ... isobutanoyl chloride, pivaloyl chloride, stearoyl chloride, crotonyl chloride, benzoyl chloride, p-nitrobenzoyl chloride, Patent; Spagnol, Michel; Gilbert, Laurent; Le Govic, Anne-Marie; US2002/120169; (2002); (A1) English View in Reaxys 8.I : Preparation of 6-Hydroxy-3-[3-methyl-4-[(1-pyrrolidinyl)-methyl]benzyl]-2-[4-(2-oxooxazolidin-4-ylmethoxy)phenyl]-benzo[b]thiophene Oxalate

105/118

2016-07-02 05:35:12

To the crude benzoyl chloride obtained and suspended in anhydrous chlorobenzene (10 mL) was added 2-dimethylamino-6-benzyloxybenzo[b]thiophene (4.92 mmol) The resultant mixture was heated in an oil bath at 110° C. for 2 h. Patent; Eli Lilly and Company; US6391901; (2002); (B1) English View in Reaxys Particular illustrative examples of acylation agents with formula (II) that can be cited are: acetic anhydride; ... isobutanoyl chloride; pivaloyl chloride; stearoyl chloride; crotonyl chloride; benzoyl chloride; p-nitrobenzoyl chloride; methoxybenzoyl chloride; naphthoyl chloride; Patent; Chimie, Rhodia; US6608232; (2003); (B1) English View in Reaxys A process according to claim 26, wherein the acylation agent is selected from the group consisting in: acetic anhydride; ... isobutanoyl chloride; pivaloyl chloride; stearoyl chloride; crotonyl chloride; benzoyl chloride; p-nitrobenzoyl chloride; methoxybenzoyl chloride; naphthoyl chloride; Patent; Chimie, Rhodia; US6608232; (2003); (B1) English View in Reaxys 1 : Preparation of 6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone EXAMPLE 1 Preparation of 6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone 1A 2-Methoxy-6-methylbenzoic acid A mixture of ethyl 2-methoxy-6-methylbenzoate (5.0 g, 25 mmol), water (10 ml), methanol (40 ml) and sodium hydroxide (2.1 g, 50 mmol) is heated under reflux with stirring. The reaction mixture is diluted with water (150 ml) and acidified with concentrated hydrochloric acid. The solid material is collected by filtration, washed with water and dried yielding dark yellow crystals, 2.1 g, mp 136° C. 1 B 2-Methoxy-6-methylbenzoyl chloride A mixture of 1A (1.7 g, 10.2 mmol) and thionyl chloride (2 ml) is heated under reflux for 1 hour. The mixture is concentrated and the resulting benzoylchloride is used without further purification. 1C 6,6'-dimethyl-2,2',3',4'-tetramethoxy-benzophenone Patent; American Cyanamid Company; US5922905; (1999); (A1) English View in Reaxys 25.A : A. A. 3,4-Diethylbenzophenone To a stirred ice bath cooled solution of diethylbenzene (1.7 mL, 10 mmol) in methylene chloride (30 mL) under nitrogen was added aluminum chloride (2.93 g, 22 mmol). A slight exotherm resulted. To the resulting reaction mixture was added benzoyl chloride (1.2 mL, 10 mmol). The reaction mixture was allowed to warm to room temperature and was then stirred at room temperature for 1.5 hours. The reaction mixture was poured into 60 mL of iced water and stirred for 20 minutes. The resulting mixture was extracted with methylene chloride (2*40 mL).

106/118

2016-07-02 05:35:12

The combined extracts were dried over magnesium sulfate and concentrated in vacuo to afford the crude product as an orange oil. Patent; Celgene Corporation; US5929117; (1999); (A1) English View in Reaxys 17 : Fluorination of benzoyl chloride EXAMPLE 17 Fluorination of benzoyl chloride A solution of benzoyl chloride (141 mg, 1 mmol) in CH2 Cl2 (5.0 mL) was added to bis(methoxyethyl)aminosulfur trifluoride (567 mg, 3.0 mmol) under N2 and stirred for 16 h at room temperature. After work-up as above benzoyl fluoride (124 mg, quantitative yield) was obtained. The product was identified by g.c.m.s. M+ =24 Patent; Air Products and Chemicals, Inc.; US6080886; (2000); (A1) English View in Reaxys 43.f : Example 43 (f) Acylation of a 2:1 or 1:2 mixture of tert-butyl (3RS,4RS)-cis- and -trans-3-naphthalen-2-ylmethoxy-4-(4-hydroxymethyl-cyclohexyl)-piperidine-1-carboxylate with benzoyl chloride yielded a 2:1 or 1:2 mixture of tert-butyl (3RS,4RS)-cisand -trans-4-(4-benzoyloxymethyl-cyclohexyl)-3-naphthalen-2-ylmethoxy-piperidine-1-carboxylate as a colourless oil; MS: 558 (M+H)+. Patent; Hoffmann-La Roche Inc.; US6051712; (2000); (A1) English View in Reaxys 100.105 : Examples 100-105 Examples 100-105 Following the procedure of Example 92, replacing the 5-bromo-6-chloro-3-(1-methyl-2-(S)-pyridinylmethoxy)pyridine starting material thereof with the starting materials shown in Table xxxxx below, and replacing the benzoyl chloride of step 92c with the acylating reagent shown in Table 3, the desired compounds 100-105 R2 and R6 as described in Table 3 are prepared. Patent; Abbott Laboratories; US6127386; (2000); (A1) English View in Reaxys 100.105 : Examples 100-105 Examples 100-105 Following the procedure of Example 92, replacing the 5-bromo-6-chloro-3-(1-methyl-2-(S)-pyridinylmethoxy)pyridine starting material thereof with the starting materials shown in Table xxxxx below, and replacing the benzoyl chloride of step 92c with the acylating reagent shown in Table 3, the desired compounds 100-105 having R2 and R6 as described in Table 3 are prepared. Patent; Abbott Laboratories; US6437138; (2002); (B1) English View in Reaxys Patent; Abbott Laboratories; US5629325; (1997); (A1) English View in Reaxys 1.8 : (8) (8) Preparation of (R)-(+)-3-fluoro-4-(1-trifluoromethyl-6-ethoxyhexyloxycarbonyl)phenyl-4-(4'-n-octyloxyphenylcarboxyloxy)benzoate 0.8 Gram of the crude benzoic acid chloride obtained in (7) and 0.7 g of the phenol derivative obtained in (4) were dissolved in 25 ml of toluene, 3 ml of pyridine was added, and the mixture was stirred at room temperature for 1 day. The reaction mixture was diluted with 150 ml of dichloromethane, consecutively washed with a 1N hydrochloric acid aqueous solution, with a 1N sodium hydroxide aqueous solution and with water and dried over anhydrous sodium sulfate, and the solvent was distilled off. Patent; Mitsubishi Gas Chemical Company, Inc.; US5723069; (1998); (A1) English View in Reaxys 18.2 : 2 2

107/118

2016-07-02 05:35:12

Diethyl 3-methyl-6-nitrobenzylmalonate A mixture of 3-methyl-2-nitrobenzylalcohol (30.0 g, 0.18 mol) and thionyl chloride (30 mL, 0.42 mol) in diethyl ether (200 mL) was refluxed for 4 h and concentrated. The residual reagent and hydrogen chloride was removed by azeotropic evaporation with toluene to give 37.0 g of the crude benzylic chloride. Patent; Sumitomo Pharmaceuticals Co., Ltd.; US5719152; (1998); (A1) English View in Reaxys 3 : Synthesis of benzoyl chloride Example 3 Synthesis of benzoyl chloride To 9.72 g (0.0575 mole) of 2-chloro-1,3-dimethylimidazolinium chloride, 90 ml of 1,2-dichloroethane and 6.11 g (0.05 mole) of benzoic acid were added. To the mixture obtained, 5.06 g (0.05 mole) of triethylamine was dropwise added over 30 minutes while maintaining the temperature of the mixture at 15°-20° C., and successively reacted at room temperature for 4 hours. The reaction mixture was analyzed by gas chromatography. The yield of benzoyl chloride was 93percent. Patent; Mitsui Toatsu Chemicals, Inc.; US5750779; (1998); (A1) English View in Reaxys 4 : Synthesis of benzoyl chloride Example 4 Synthesis of benzoyl chloride To a four necked flask equipped with a stirrer, gas inlet tube, thermometer and Dimroth condenser, 3.42 g (0.03 mole) of 1,3-dimethylimidazolidine-2-one as a catalyst, 36.64 (0.3 mole) of benzoic acid, and 146.56 g of toluene were charged. Phosgene was blown into the mixture with stirring at a rate of 4.2 g/hour, and the reaction was carried out at 110° C. for 7 hours. The reaction mass was analyzed by gas chromatography. The yield of benzoyl chloride was 95percent. Patent; Mitsui Toatsu Chemicals, Inc.; US5750779; (1998); (A1) English View in Reaxys According to the first process of the invention, the bis-(indolyl)ethylenes, (I) for example, are prepared by condensing the indoles (J1) through (J4) with acid anhydride [(ZCH2 CO)20 ] in the presence of compounds belonging to: Carboxylic Acids (e.g. Acetic Acid); or Benzoyl Chloride); or Zinc Chloride, Boron Trifluoride) Patent; Appleton Papers Inc.; US4996328; (1991); (A1) English View in Reaxys 10 : (Conversion of Substituted Benzoic Acids to Substituted Benzoyl Chlorides) PREPARATION 10 (Conversion of Substituted Benzoic Acids to Substituted Benzoyl Chlorides) To a solution or suspension of the appropriately substituted benzoic acid in ethyl acetate is added 1.5 equivalents of oxalyl chloride and a trace of dimethyl formamide. The reaction mixture is stirred at room temperature for several hours until gas evolution is complete and a homogenous solution is obtained. Concentration of the solution under reduced pressure affords the corresponding benzoyl chloride. Patent; Syntex (U.S.A.) Inc.; US5034410; (1991); (A1) English View in Reaxys ...hylenes, are prepared by condensing an indole, which can be substituted with any of one or more of R5, R6, A or B, with acid anhydride [(ZCH2 CO)2 O] in the presence of an electron acceptor or acidic type compounds belonging to: Carboxylic Acids (e.g. Acetic Acid); or Benzoyl Chloride); or Zinc Chloride, Boron Trifluoride)

108/118

2016-07-02 05:35:12

Patent; Appleton Papers Inc.; US5086171; (1992); (A1) English View in Reaxys The following compounds of the formula IV may be mentioned individually: benzoyl chloride, 4-chlorobenzoyl chloride, 4-trifluoromethoxybenzoyl chloride, 4-trifluoromethylbenzoyl chloride, 2,6-dichlorobenzoyl chloride, 3-chloro-4-trifluoromethylbenzoyl chloride, 2,4,6-trimethylbenzoyl chloride, dimethylcarbamoyl chloride, N-methyl-N-phenylcarbamoyl chloride, ... Patent; Bayer Aktiengesellschaft; US4804655; (1989); (A1) English View in Reaxys 1 : EXAMPLE 1 EXAMPLE 1 30 g of 2-fluoro-4-decyloxyl benzoic acid (prepared from 2-fluoro-4-hydroxybenzoic acid with decyl bromide in DMF/ potassium carbonate) are refluxed with 15 g of thionyl chloride in 120 ml of toluene until the evolution of hydrogen chloride is complete, and then converted into the corresponding benzoyl chloride, and a mixture of 28.4 g of 4-(5octylpyrimidin-2-yl)-phenyl and 10 ml of triethylamine is added. Patent; Merck Patent Gesellschaft Mit Beschrankter Haftung; US4820839; (1989); (A1) English View in Reaxys 39 : EXAMPLE 39 The product obtained in Paragraph (1-a) or (1-b) and benzoyl chloride (0.85 g) are treated in the same manner as described in Example 1-(2), whereby the following compounds are obtained. Patent; Tanabe Seiyaku Co., Ltd.; US4857543; (1989); (A1) English View in Reaxys The process of claim 1 wherein the activating agent of step (3) is selected from the group consisting of: thionyl chloride, phosphorus trihalides; Ph3 P--Br2 complex; ... Ph3 P--CCl4; paratoluene sulfonyl chloride; methanesulfonyl chloride trifluoromethane sulfonyl chloride; trifluoromethane sulfonic anhydride; methyl iodide; acetyl chloride; benzoyl chloride; Patent; Eastman Kodak Company; US4879416; (1989); (A1) English View in Reaxys 4 : EXAMPLE 4 EXAMPLE 4 Using Method 1, Chemical A, 1,2-bis[4-(alphaaminobenzyl)phenoxy]ethane, is prepared by the procedure of Example 1, starting with 1,2-diphenoxyethane and benzoyl chloride; mp 116°-120°. Calculated for C28 H28 N2 O2: C, 79.21percent; H, 6.65percent; N, 6.60percent. Found: C, 79.29percent; H, 6.52percent; N, 6.39percent. Patent; Uniroyal, Inc.; Uniroyal Ltd.; US3954868; (1976); (A1) English View in Reaxys By following the above procedure, and substituting for the stearoyl chloride an equivalent amount of: a. oxalyl dichloride b. benzoyl chloride c. phthaloyl chloride d. isophthaloyl chloride

109/118

2016-07-02 05:35:12

e. terephthaloyl chloride Patent; Ciba-Geigy Corporation; US4007156; (1977); (A1) English View in Reaxys amidoxime thioformate benzoyl chloride thioformate Patent; E. R. Squibb and Sons, Inc.; US3976657; (1976); (A1) English View in Reaxys Examples of an acid halide of the Formula III or IV are as follows: ... Propionyl chloride Butyryl chloride Isobutyryl chloride Cyclohexane carbonyl chloride Benzoyl chloride Benzoyl bromide p-Anisoyl chloride p-Chlorobenzoyl chloride ... Patent; Sumitomo Chemical Company, Limited; US4055565; (1977); (A1) English View in Reaxys 1 : EXAMPLE 1 EXAMPLE 1 There were mixed in a reaction vessel provided with a reflux condenser 140.5 grams (1.0 mole) of benzoyl chloride, 54 grams (1.1 mole) of sodium cyanide, 9 grams (0.1 mole) of copper (I) cyanide, 25 ml of xylene and 7.5 ml (0.14 mole) of acetonitrile. The mixture was heated to 130° C. with stirring. The mixture was held for 3 hours at this temperature and then cooled to 15° C. The salts separated thereby, chiefly sodium chloride, were filtered off and washed with 25 ml of xylene. The filtrate was fractionally distilled under reduced pressure. There were recovered 119.5 grams of pure benzoyl cyanide, corresponding to a yield of 91percent based on the benzoyl chloride employed. The benzoyl cyanide had a boiling point of 113° to 117° C. at 43 mbar. Patent; Deutsche Gold- und Silber-Scheideanstalt Vormals Roessler; US4113773; (1978); (A1) English View in Reaxys The process in claim 20 in which said mixing is with an electrophile from the group consisting of acrylonitrile; methyl benzoate; phenyl isocyanate; isopropyl bromide; benzoyl chloride; methyl acrylate. Patent; Reilly Tar and Chemical Corporation; US4158093; (1979); (A1) English View in Reaxys 44.E : Step E Step E Using the method of Example 1, Step A, 4-(2-nitro-3-benzofuranyl)benzoic acid is reacted with thionyl chloride to provide the corresponding benzoyl chloride, which is further reacted with sodium azide to provide the azide intermediate. Patent; Riker Laboratories, Inc.; US4212865; (1980); (A1) English View in Reaxys 33 : Example 33

110/118

2016-07-02 05:35:12

The product obtained in Paragraph (1-a) or (1-b) and benzoyl chloride (0.85 g) are treated in the same manner as described in Example 1-(2), whereby the following compounds are obtained. Patent; TANABE SEIYAKU CO., LTD.; EP297782; (1991); (B1) English View in Reaxys Illustrative examples of acylation agents with formula (VIII) which can in particular be cited are: ... isobutanoyl chloride; pivaloyl chloride; stearoyl chloride; crotonyl chloride; benzoyl chloride; p-nitrobenzoyl chloride; o-nitrobenzoyl chloride;; benzoic anhydride. Patent; Mioskowski, Charles; Wagner, Alain; Bensel, Nicolas; Pevere, Virginie; Desmurs, Jean-Roger; US2003/92946; (2003); (A1) English View in Reaxys Using a procedure analogous to Example 2, the following compounds may be reacted with 2-amino-N-[1-[2-(1H-indol-3-yl)ethyl]-4-piperidinyl]-acetamide (a) benzoyl chloride (b) 4-chlorobenzoyl chloride (c) 4-methoxybenzoyl chloride (d) 2-thenoyl chloride (e) 3-methylbenzoyl chloride Patent; John Wyeth and Brother Limited; US4443461; (1984); (A1) English View in Reaxys To give an idea of the acylation agents that match formula (II) we can the following in particular: ... isobutanoyl chloride, pivaloyl chloride, stearoyl chloride, crotonyl chloride, benzoyl chloride, chlorobenzoyl chloride, p-nitrobenzoyl chloride, methoxybenzoyl chloride, Patent; Rhodia Chimie; US6184418; (2001); (B2) English View in Reaxys 17 : Fluorination of Benzoyl Chloride EXAMPLE 17 Fluorination of Benzoyl Chloride A solution of benzoyl chloride (141 mg, 1 mmol) in CH2Cl2 (5.0 mL) was added to bis(methoxyethyl)aminosulfur trifluoride (567 mg, 3.0 mmol) under N2 and stirred for 16 h at room temperature. After work-up as above benzoyl fluoride (124 mg, quantitative yield) was obtained. The product was identified by g.c.m.s. M+=124 Patent; Air Products and Chemicals, Inc.; US6222064; (2001); (B1) English View in Reaxys Particular illustrative examples of acylation agents with formula (II) are: acetic anhydride; ... isobutanoyl chloride; pivaloyl chloride; stearoyl chloride;; crotonyl chloride;

111/118

2016-07-02 05:35:12

benzoyl chloride; p-nitrobenzoyl chloride; Patent; Rhodia Chimie; US6194616; (2001); (B1) English View in Reaxys 31 : (5-Chloro-2-{2-[4-(4-Fluoro-Benzyl)-(2R,5S)-2,5-Dimethyl-Piperazin-1-Yl]-2-Oxo-Ethoxy}-Benzylfulfnayl)Acetic Acid Methyl Ester (5-Chloro-2-{2-[4-(4-Fluoro-Benzyl)-(2R,5S)-2,5-Dimethyl-Piperazin-1-Yl]-2-Oxo-Ethoxy}-Benzylfulfnayl)-Acetic Acid Methyl Ester To 2-(4-chloro-2-hydroxymethyl-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.50 g, 1.19 mmol) was added thionyl chloride (3 ml). The reaction was heated to reflux for 3 hours. After concentration the benzylic chloride was isolated by chromatography on silica gel (0.27 g). Patent; Pfizer Inc; US2004/92529; (2004); (A1) English View in Reaxys 1.H : Step H Thionyl chloride (0.42 g, 3.5 mmol) was added to a solution of the benzoic acid from Step G (0.50 g, 2.4 mmol) in 10 mL of toluene at room temperature. The reaction was refluxed for three hours then cooled to room temperature. The solvent was evaporated under reduced pressure and excess thionyl chloride was removed by azeotroping with toluene. The benzoyl chloride obtained was used directly in Step I. Patent; Annis, Gary David; Myers, Brian James; Selby, Thomas Paul; Stevenson, Thomas Martin; Zimmerman, William Thomas; US2004/110777; (2004); (A1) English View in Reaxys 13.B : PREPARATION OF 9-BROMO-3-(4-FLUOROBENZOYL)-1,2,3,6-TETRAHYDROAZEPINO[4,5-B]INDOLE-5-CARBOXYLIC ACID ETHYL ESTER B. In a similar manner, but replacing 4-fluorobenzoyl chloride with the appropriate benzoyl chloride, the following compounds were prepared: 9-bromo-3-(3-fluorobenzoyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester; MS (ESI): 457, 459 (MH+); 9-bromo-3-(2-fluorobenzoyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester; MS (ESI): 457, 459 (MH+); 3-benzoyl-9-bromo-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester; MS (ESI): 439, 441 (MH+); 9-bromo-3-(4-chlorobenzoyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester; MS (ESI): 473, 475 (MH+); and 9-bromo-3-(3-chlorobenzoyl)-1,2,3,6-tetrahydroazepino[4,5-b]indole-5-carboxylic acid ethyl ester;MS (ESI): 473, 475 (MH+). Patent; Busch, Brett; Flatt, Brenton T.; Gu, Xiao-Hui; Martin, Richard; Mohan, Raju; Wang, Tie-Lin; Wu, Jason H.; US2005/54634; (2005); (A1) English View in Reaxys

H N

N H

O N

N H

Rx-ID: 5989447 View in Reaxys 276/294

112/118

2016-07-02 05:35:12

Yield

Conditions & References Stolz; Journal fuer Praktische Chemie (Leipzig); vol. <2> 55; (1897); p. 154 View in Reaxys

N O O

Rx-ID: 24075473 View in Reaxys 277/294 Yield 59%

Conditions & References 3.D : Preparation of (S)-3-[4-[2-(1-Pyrrolidinyl)ethoxy]benzyl]-2-[4-(5-oxopyrrolidin-2-ylmethoxy)phenyl]benzo[b]thiophene Oxalate Part D. 2-(4-Methoxyphenyl)benzo[b] thiophen-3-yl 4-[2-(1-Pyrrolidinyl)ethoxy]phenyl Ketone. By essentially following the procedure detailed in Example 1, Part D, but using thionyl chloride in refluxing dichloromethane to form the benzoyl chloride, the title compound was prepared from 2-(4-methoxyphenyl)-benzo[b]thiophene and 4-[2-(1-pyrrolidinyl)ethoxy]benzoic acid hydrochloride in 59percent yield as an oil following radial chromatography (SiO2; gradient of 2-5percent MeOH in CH2Cl2). Patent; Eli Lilly and Company; US6391901; (2002); (B1) English View in Reaxys

O O

Rx-ID: 41685634 View in Reaxys 278/294 Yield

Conditions & References 2 : Preparation of (2R,3R,4S,5R,6R)-2-chloro-6-(benzoyloxymethyl)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate Example 2 Preparation of (2R,3R,4S,5R,6R)-2-chloro-6-(benzoyloxymethyl)tetrahydro-2H-pyran-3,4,5-triyl tribenzoate Zinc chloride (164.7 mg, 1.21 mmol) was added to a mixture comprising benzoyl chloride (7.84 g, 55.77 mmol), Dglucose (1.00 g, 5.55 mmol) and dichloromethane (10 mL), and the resulting mixture was stirred under ice-cooling for 18 hours. After raising the temperature of the mixture to room temperature, the mixture was stirred for further 26 hours. After raising the temperature of the mixture to 40° C. and stirring for 2 hours, the reaction mixture was washed with water under ice-cooling. The obtained organic layer was washed twice with a 10percent aqueous sodium hydrogencarbonate solution, and dried over magnesium sulfate. After the organic layer was further washed with water, a 10percent aqueous sodium hydrogencarbonate solution was added to the same and the resulting mixture was stirred at 40° C. for 13.5 hours. The separated organic layer was dried over magnesium sulfate, filtered and then concentrated. The concentrated residue was purified by column chromatography (SH silica gel, hexane/ethyl acetate) to obtain the title compound (2.93 g, Yield: 86percent). With Zinc chloride

113/118

2016-07-02 05:35:12

Patent; MITSUBISHI TANABE PHARMA CORPORATION; UEDA, Keita; HATSUDA, Masanori; HYODO, Isao; TANIMOTO, Kouichi; (13 pag.); US2016/2276; (2016); (A1) English View in Reaxys [1(R)]-α-[3-amino-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-2-oxo-1-pyrrolidinyl]-N-hydroxy-1-(phenylcarbonyl)-4-piperidineacetamide bis(trifluoroacetate)

O Cl

Rx-ID: 24294660 View in Reaxys 279/294 Yield

Conditions & References [1(R)]-α-[3-amino-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-2-oxo-1-pyrrolidinyl]-N-hydroxy-1-(phenylcarbonyl)-4-piperidineacetamide bis(trifluoroacetate) [1(R)]-α-[3-amino-3-[4-[(2,6-dimethyl-4-pyridinyl)methoxy]phenyl]-2-oxo-1-pyrrolidinyl]-N-hydroxy-1-(phenylcarbonyl)-4-piperidineacetamide bis(trifluoroacetate) Beginning with the piperidine from (505a) and benzoyl chloride, example 526 was prepared in an analogous series of reactions to (49a) and (92d). MS found: (M+H)+ =572. Patent; E. I. du Pont de Nemours and Company; US6057336; (2000); (A1) English View in Reaxys O

Rx-ID: 25283178 View in Reaxys 280/294 Yield

Conditions & References 6 : EXAMPLE 6 EXAMPLE 6 Benzotrichloride (195.5 g), acetic anhydride (98 g) and sulfuric acid were charged to the reactor. Acetyl chloride began to distill when the reaction mixture reached 118° C. The yield of acetyl chloride was 130 g (86.3percent) and the yield of benzoyl chloride was 130.9 g (93.1percent), b.p. 191°-193° C. Patent; Diaz Chemical Corporation; US4163753; (1979); (A1) English View in Reaxys 9 : EXAMPLE 9 EXAMPLE 9 In this run, the addition procedure was reversed with the benzotrichloride being added to the acetic anhydride and sulfuric acid over a 3 hour period. The yield of acetyl chloride was 145.59 (92.8percent) and the yield of benzoyl chloride was 102 gms (72.6percent). Patent; Diaz Chemical Corporation; US4163753; (1979); (A1) English View in Reaxys 18O

Rx-ID: 7625348 View in Reaxys 281/294 Yield

Conditions & References Denney et al.; Journal of the American Chemical Society; vol. 83; (1961); p. 1726 View in Reaxys Knorr; Chemische Berichte; vol. 104; (1971); p. 3633,3635,3640 View in Reaxys Shapiro; Tomer; Organic Mass Spectrometry; vol. 3; (1970); p. 333,335 View in Reaxys Pinchas et al.; Journal of the Chemical Society; (1961); p. 2382,2383-2385, 2387 View in Reaxys Neumann; Ruebsamen; Chemische Berichte; vol. 100; (1967); p. 1621 View in Reaxys Gash; Yuen; Journal of Organic Chemistry; vol. 34; (1969); p. 720 View in Reaxys

114/118

2016-07-02 05:35:12

Cl O S NH H N

Rx-ID: 24461550 View in Reaxys 282/294 Yield

Conditions & References 6 : 1-[3-[2-(4-Chlorophenylsulphonylamino)-ethyl]-phenoxy]-2-acetaminoethane Example 6 1-[3-[2-(4-Chlorophenylsulphonylamino)-ethyl]-phenoxy]-2-acetaminoethane One stirs a suspension of 2.0 g (5.1 mmol) 1-[3-[2-(4-chlorophenylsulphonylamino)-ethyl]-phenoxy]-2-aminoethane hydrochloride (see Example 1), 50 ml methylene chloride and 1.56 g (15.3 mmol) abs. triethylamine for 15 min, adds thereto a catalytic amount of 4-dimethylaminopyridine and cools to 0° C. A solution of 0.4 g (5.1mmol) acetyl chloride and 4 ml abs. methylene chloride is now added theretodropwise. After two hours, one extracts twice with dil. HCl and then with water, dries with MgSO4 and evaporates. The oil remaining behind is chromatographed on silica gel with the elution agent methylene chloride. After evaporation, one obtains a colourless oil, yield 1.3 g (64percent of theory). In an analogous manner, one obtains with benzoyl chloride Patent; Boehringer Mannheim GmbH; US5446065; (1995); (A1) English View in Reaxys O

N O

NH 2

Rx-ID: 24664110 View in Reaxys 283/294 Yield

Conditions & References 11.a : (a) (a) N-(4nitrobenzyl)benzamide) This compound was prepared following the method of Example 10, step (a). From 4-nitrobenzyl amine (2.45 g, 0.013 mol) and benzoyl chloride (2.1 g, 0.0149 mol) was isolated 2.56 g (77percent) of the title product, m.p. 150°-3° C. Patent; Astra Aktiebolag; US5807885; (1998); (A1) English View in Reaxys

Rx-ID: 24667261 View in Reaxys 284/294 Yield

Conditions & References 1 : Example 1 Excess oxalylchloride was removed under vacuum and traces of it were removed under high vacuum. The resulting benzoyl chloride (VII) and 4-n-decyloxyphenol (VIII) (10 mmol) were dissolved in dry cold (0° C.) THF. Triethylamine (30 mmol) was added dropwise, followed by a catalytic amount of DMAP. The reaction mixture was stirred with a magnetic stir bar for three hours at room temperature. The solvent was then rotary evaporated and the residue was passed through a thick pad of silica using 20percent (v/v) hexanes in CH2 Cl2. Patent; University Research Corporation; US5167855; (1992); (A1) English View in Reaxys

115/118

2016-07-02 05:35:12

F HO

O O

Rx-ID: 25060044 View in Reaxys 285/294 Yield

Conditions & References 32 : EXAMPLE 32 EXAMPLE 32 In a manner analogous to example 5, when 4-methyl-3,3-difluoro-1,4-pentanediol, is reacted with pyridine and benzoyl chloride, 4-methyl-3,3-difluoro-1,4-pentanediol 1-benzoate can be obtained. Patent; Hoffmann-La Roche Inc.; US4421690; (1983); (A1) English View in Reaxys O 13C

Rx-ID: 7248243 View in Reaxys 286/294 Yield

Conditions & References Grundmann,C. et al.; Justus Liebigs Annalen der Chemie; vol. 761; (1972); p. 162 - 181 View in Reaxys Kepler et al.; Journal of Labelled Compounds; vol. 10; (1974); p. 683,685 View in Reaxys Casanova et al.; Organic Preparations and Procedures International; vol. 1; (1969); p. 81,82 View in Reaxys Casanova Jun. et al.; Journal of the American Chemical Society; vol. 91; (1969); p. 2156 View in Reaxys O 14C

Rx-ID: 7178216 View in Reaxys 287/294 Yield

Conditions & References Benzoesaeure-(carboxyl-14C) nach: Heidelberger, Rieke 'Org. Synth. with Isotopes', Pt.1, A. Murray and D. L. Williams, Eds., Interscience Publishers, Inc., N. Y. C. , 1958, p. 379. Merrill; Vernice; Journal of Labelled Compounds; vol. 7; (1971); p. 89,94 View in Reaxys Benzoesaeure-14C, SOCl2 McEwen et al.; Journal of Organic Chemistry; vol. 32; (1967); p. 1947,1952 View in Reaxys entspr. Saeure, SOCl2 Gamboa et al.; Anales de la Real Sociedad Espanola de Fisica y Quimica, Serie B: Quimica; vol. 57; (1961); p. 607,612 View in Reaxys Phenylmagnesiumbromid, 1.) 14CO2, 2.) SOCl2, 1 h, 65grad Schmidt; Werner; Justus Liebigs Annalen der Chemie; vol. 653; (1962); p. 184,192 View in Reaxys /BRN= 938559/, SOCl2 Fillion et al.; Bulletin de la Societe Chimique de France; (1974); p. 2923 View in Reaxys nach Heidelberger aus Benzoesaeure, (14C)CO Engler et al.; Acta Chimica Academiae Scientiarum Hungaricae; vol. 59; (1969); p. 411

116/118

2016-07-02 05:35:12

View in Reaxys (yield)81.7percent Engler et al.; Acta Chimica Academiae Scientiarum Hungaricae; vol. 59; (1969); p. 411 View in Reaxys 2H

O 2H

Cl 2H

Rx-ID: 7188737 View in Reaxys 288/294 Yield

Conditions & References Deady; Stillmann; Australian Journal of Chemistry; vol. 32; (1979); p. 381,384 View in Reaxys Beak et al.; Journal of the American Chemical Society; vol. 98; (1976); p. 3621,3622, 3625 View in Reaxys Buu-Hoi et al.; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 255; (1962); p. 3490 View in Reaxys O 14C

Rx-ID: 7277515 View in Reaxys 289/294 Yield

Conditions & References Multi-Step-Synthese der Saeure aus Ba14CO3 u. anschl. Ums. mit SOCl2 Kim,S.-G. et al.; Bulletin of the Chemical Society of Japan; vol. 52; (1979); p. 1115 - 1120 View in Reaxys O 2H

Rx-ID: 7387541 View in Reaxys 290/294 Yield

Conditions & References 4-Deuterobenzoesaeure, Thionylchlorid McBride; Gisler; Molecular Crystals and Liquid Crystals (1969-1991); vol. 52; (1979); p. 121,125-127 View in Reaxys Aus der entspr. Saeure m. SOCl2 Grundmann,C. et al.; Justus Liebigs Annalen der Chemie; vol. 761; (1972); p. 162 - 181 View in Reaxys

Rx-ID: 7389188 View in Reaxys 291/294 Yield

Conditions & References Benzoe-2,5-d(2) saeure, SOCl2 Whitesides et al.; Journal of Organometallic Chemistry; vol. 22; (1970); p. 365,367, 372 View in Reaxys

117/118

2016-07-02 05:35:12

O 2H

Cl 2H

Rx-ID: 8050719 View in Reaxys 292/294 Yield

Conditions & References (2.4.6-D3)Benzoesaeure, SOCl2 Bowie et al.; Tetrahedron; vol. 24; (1968); p. 3965 View in Reaxys 2H

O Cl 2H

Rx-ID: 7654856 View in Reaxys 293/294 Yield

Conditions & References Benzoesaeure-2,6-d(2), SOCl2 Renaud et al.; Canadian Journal of Chemistry; vol. 39; (1961); p. 21 View in Reaxys O Cl

2H 2H

Rx-ID: 7654857 View in Reaxys 294/294 Yield

Conditions & References Benzoesaeure-2,3-d(2), SOCl2 Renaud et al.; Canadian Journal of Chemistry; vol. 39; (1961); p. 21 View in Reaxys

118/118

2016-07-02 05:35:12