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13 reactions in Reaxys
2016-08-08 00h:27m:45s (EST)
N
1. Query O
Search as: As drawn, No mixtures, No charges, No radicals
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N O
O
N
O
Rx-ID: 577949 View in Reaxys 1/13 Yield 87 %
Conditions & References 67.1 :Step 1. 3-Oxo-2-phenylbutanenitrile To a solution of 2-phenylacetonitrile (20.4 g, 174.14 mmol) in ethyl acetate (400 mL) was added sodium (5.6 g, 243.59 mmol). After stirring 14 hours at 80° C., the solids were collected by filtration and dissolved in water (150 mL), the pH was adjusted to 5 with HCl (3N), extracted with ethyl acetate (2*200 mL), and the organic layers were dried over anhydrous magnesium sulfate and concentrated in vacuo to afford 3-oxo-2-phenylbutanenitrile as a light yellow solid (24.2 g, 87percent). 1H-NMR (300 MHz, CDCl ) δ 7.40-7.50 (m, 5H), 4.70 (s, 1H), 2.29 (s, 3H) 3 With sodium, Time= 14h, T= 80 °C , Product distribution / selectivity Patent; BIOENERGENIX; US2012/277224; (2012); (A1) English View in Reaxys
31 %
Stage 1: With lithium hexamethyldisilazane in tetrahydrofuran, diethyl ether, Time= 0.166667h, T= -78 °C Stage 2: in tetrahydrofuran, diethyl ether, Time= 72h, T= 20 °C , Further stages. El-Hamamsy, Mervat H.R.I.; Smith, Anthony W.; Thompson, Andrew S.; Threadgill, Michael D.; Bioorganic and Medicinal Chemistry; vol. 15; nb. 13; (2007); p. 4552 - 4576 View in Reaxys
9%
161 :A 25 g (0.213 mol) portion of phenylacetonitrile and 33 ml of ethyl acetate were added to an ethanol solution of sodium ethoxide prepared from ethanol (150 ml) and 6.38 g (0.277 mol) of metallic sodium and then heated under reflux for 3 hours. After cooling, this was concentrated under a reduced pressure, and the thus obtained residue was mixed with water and dichloromethane to separate the organic layer. This was washed with 1 N hydrochloric acid and brine and dried over magnesium sulfate, and then the solvent was evaporated. The thus obtained residue was applied to a silica gel column chromatography to obtain 3.15 g (9percent) of the title compound as a colorless oily substance from a n-hexane-ethyl acetate (5:1-->3:1 v/v) eluate. MS (FAB)m/z: 160 (M+1)+. 1H-NMR (CDCl3)δ: 2.27 (3H, s), 4.68 (1H, s), 7.36-7.52 (5H, m). Stage 1: With ethanol, sodium Stage 2: in ethanol, Time= 3h, Heating / reflux Patent; DAIICHI PHARMACEUTICAL CO., LTD.; EP1717238; (2006); (A1) English View in Reaxys With sodium ethanolate Beckh; Chemische Berichte; vol. 31; (1898); p. 3163 View in Reaxys Walther; Schickler; Journal fuer Praktische Chemie (Leipzig); vol. <2> 55; (1897); p. 323 View in Reaxys Julian et al.; Organic Syntheses; vol. 18; (1938); p. 66; Organic Syntheses; vol. Coll. Vol. II; (1943); p. 487 View in Reaxys With sodium ethanolate in ethanol, Heating Furukawa,M. et al.; Chemical and Pharmaceutical Bulletin; vol. 9; (1961); p. 914 - 921 View in Reaxys With sodium hydride in ethylene glycol dimethyl ether Aspart-Pascot,L.; Lematre,J.; Bulletin de la Societe Chimique de France; (1971); p. 483 - 490 View in Reaxys Stage 1: With sodium hydride in tetrahydrofuran Stage 2: in tetrahydrofuran
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Chen, Chen; Wilcoxen, Keith M.; Huang, Charles Q.; McCarthy, James R.; Chen, Takung; Grigoriadis, Dimitri E.; Bioorganic and Medicinal Chemistry Letters; vol. 14; nb. 14; (2004); p. 3669 - 3673 View in Reaxys With sodium ethanolate Pavlik, James W.; St. Martin, Heather; Lambert, Karen A.; Lowell, Jennifer A.; Tsefrikas, Vikki M.; Eddins, Cheryl K.; Kebede, Naod; Journal of Heterocyclic Chemistry; vol. 42; nb. 2; (2005); p. 273 - 281 View in Reaxys With sodium hydride in tetrahydrofuran, T= 0 - 60 °C Du, Yunfei; Liu, Renhe; Linn, Gregory; Zhao, Kang; Organic Letters; vol. 8; nb. 26; (2006); p. 5919 - 5922 View in Reaxys With sodium hydride in tetrahydrofuran Qi, Jinlong; Zhang, Fan; Mi, Yi; Fu, Yan; Xu, Wen; Zhang, Diqun; Wu, Yibing; Du, Xiaona; Jia, Qingzhong; Wang, Kewei; Zhang, Hailin; European Journal of Medicinal Chemistry; vol. 46; nb. 3; (2011); p. 934 - 943 View in Reaxys N O
O
O
N
O
O
O
Rx-ID: 36721729 View in Reaxys 2/13 Yield
Conditions & References
26 %, 21 %
4.5 Typical procedure for reaction of esters with cyanides to β-ketonitriles 9 under the optimized conditions General procedure: Ethyl ester 1 (6.65 mmol, 1 equiv) was dissolved in THF (30 mL, technical grade involving 0.2percent water) with stirring (about 230rpm) at ambient temperature for 5min. Potassium tert-butoxide (1.57 g, 14.0 mmol, 95percent, 2 equiv) was added immediately to the above THF solution. After stirring enough the flask, the corresponding cyanide 8 (6.65mmol, 1equiv) was then added. The resulting mixture was stirred at ambient temperature. The reaction mixture was quenched by addition of water (50mL) and then stirred for 5min. After adding ethyl acetate (40 mL) and then HCl solution (1 mL, 12 M), the organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was applied to the top of an open-bed silica gel column (for 9a–e, 9g–j: 3×15cm, n-hexane/ethyl acetate (3:1, v/v); for 9f: 3.5×8 cm, CH2Cl2). Fractions containing the product were combined and evaporated under reduced pressure to give the corresponding β-ketonitriles. Stage 1: With potassium tert-butylate in tetrahydrofuran, water Stage 2: in tetrahydrofuran, water, Time= 0.5h, T= 20 °C Kim, Bo Ram; Lee, Hyung-Geun; Kang, Seung-Beom; Jung, Kwang-Ju; Sung, Gi Hyeon; Kim, Jeum-Jong; Lee, Sang-Gyeong; Yoon, Yong-Jin; Tetrahedron; vol. 69; nb. 48; (2013); p. 10331 - 10336 View in Reaxys N
O
O–
F
Cl N
S
F F
O
O
I+
Si
O
Rx-ID: 10428708 View in Reaxys 3/13 Yield 78 %
Conditions & References Stage 1: With n-butyllithium in tetrahydrofuran, Time= 0.25h, T= -78 °C Stage 2: With tetrabutyl ammonium fluoride in tetrahydrofuran, Time= 0.916667h, T= 0 - 20 °C Stage 3: in tetrahydrofuran, Time= 0.5h, T= 0 °C Kamila, Sukanta; Koh, Benjamin; Biehl, Edward R.; Synthetic Communications; vol. 36; nb. 23; (2006); p. 3493 3507 View in Reaxys
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N
O
Cl
N
O
Rx-ID: 3973789 View in Reaxys 4/13 Yield
Conditions & References With lithium diisopropyl amide, 1.) THF, -50 deg C, 3 h, 2.) THF, -78 deg C to 0 deg C, Yield given. Multistep reaction Itoh; Fukuda; Fujisawa; Bulletin of the Chemical Society of Japan; vol. 62; nb. 12; (1989); p. 3851 - 3855 View in Reaxys Stage 1: With lithium diisopropyl amide in tetrahydrofuran, Time= 0.166667h, T= -78 °C Stage 2: in tetrahydrofuran, T= -78 °C , Further stages. Tarnchompoo, Bongkoch; Sirichaiwat, Chawanee; Phupong, Worrapong; Intaraudom, Chakapong; Sirawaraporn, Worachart; Kamchonwongpaisan, Sumalee; Vanichtanankul, Jarunee; Thebtaranonth, Yodhathai; Yuthavong, Yongyuth; Journal of Medicinal Chemistry; vol. 45; nb. 6; (2002); p. 1244 - 1252 View in Reaxys
N N N
O O
O
Rx-ID: 9937977 View in Reaxys 5/13 Yield 80 %, 18 %
Conditions & References in methanol, Time= 0.166667h, Irradiation Pavlik, James W.; St. Martin, Heather; Lambert, Karen A.; Lowell, Jennifer A.; Tsefrikas, Vikki M.; Eddins, Cheryl K.; Kebede, Naod; Journal of Heterocyclic Chemistry; vol. 42; nb. 2; (2005); p. 273 - 281 View in Reaxys N
N
O
Rx-ID: 578234 View in Reaxys 6/13 Yield
Conditions & References With diethyl ether, triphenylmethyl-sodium, anschliessend Behandeln mit Acetylchlorid Mueller; Gawlick; Kreutzmann; Justus Liebigs Annalen der Chemie; vol. 515; (1935); p. 100,109 View in Reaxys N
O O
O
Rx-ID: 22248181 View in Reaxys 7/13 Yield
Conditions & References Reaction Steps: 2 1: ethanol; NH2OH+HCl 2: ethanol With hydrogenchloride, ethanol, hydroxylamine Yasuda; Yakugaku Zasshi; vol. 79; (1959); p. 623,626; ; (1959); p. 21885 View in Reaxys
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N O– Na +
N
O O
Rx-ID: 83167 View in Reaxys 8/13 Yield
Conditions & References With ethanol Yasuda; Yakugaku Zasshi; vol. 79; (1959); p. 623,626; ; (1959); p. 21885 View in Reaxys N
O
O
monosodium-compound of benzyl cyanide O
Rx-ID: 6047783 View in Reaxys 9/13 Yield
Conditions & References Bodroux; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 151; (1910); p. 235; Bulletin de la Societe Chimique de France; vol. <4> 7; (1910); p. 847,850 View in Reaxys
O
O
N
H C–
O
Na +
N
O
Rx-ID: 570291 View in Reaxys 10/13 Yield
Conditions & References Bodroux; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 152; (1911); p. 1594; Bulletin de la Societe Chimique de France; vol. <4> 9; (1911); p. 726 View in Reaxys N O
O– Na +
O
N
O
Rx-ID: 577948 View in Reaxys 11/13 Yield
Conditions & References Beckh; Chemische Berichte; vol. 31; (1898); p. 3163 View in Reaxys Walther; Schickler; Journal fuer Praktische Chemie (Leipzig); vol. <2> 55; (1897); p. 323 View in Reaxys N
H C–
O
Cl
Na +
N
O
Rx-ID: 692672 View in Reaxys 12/13 Yield
Conditions & References Bodroux; Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences; vol. 152; (1911); p. 1594; Bulletin de la Societe Chimique de France; vol. <4> 9; (1911); p. 726 View in Reaxys N
O
Rx-ID: 6047782 View in Reaxys 13/13
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Yield 62 %
Conditions & References 8.1 : Stage 8.1 3-Oxo-2-phenyl-butyronitrile 3-Oxo-2-phenyl-butyronitrile is prepared analogously to the preparation of compound of Stage 1.3: 62percent, white crystals, m.p. >215° C.; ES-ES-MS M-H=157.9, Rf(hexane/AcOEt=1:1)=0.57. 1H-NMR (400 MHz, DMSO-d6): 7.84 (d, 9.0 Hz, 2H), 7.04 (t, 9.0 Hz, 2H), 6.68 (t, 9.0 Hz, 1H), 3.21 (s/broad, 1H, CH), 2.03 (s, 3H, CH3). Patent; Bold, Guido; Floersheimer, Andreas; Furet, Pascal; Imbach, Patricia; Masuya, Keiichi; Schoepfer, Joseph G.; US2005/222171; (2005); (A1) English View in Reaxys
62 %
8.1 Patent; NOVARTIS AG; NOVARTIS PHARMA GMBH; WO2005/70431; (2005); (A1) English View in Reaxys
62 %
8.1 : Stage 8.1 3-Oxo-2-phenyl-butyronitrile Stage 8.1 3-Oxo-2-phenyl-butyronitrile 3-Oxo-2-phenyl-butyronitrile is prepared analogously to the preparation of compound of Stage 1.3: 62percent, white crystals, m.p. >215° C.; ES-ES-MS M-H=157.9, Rf (hexane/AcOEt=1:1)=0.57. 1H-NMR
(400 MHz, DMSO-d6): 7.84 (d, 9.0 Hz, 2H), 7.04 (t, 9.0 Hz, 2H), 6.68 (t, 9.0 Hz, 1H), 3.21 (s/broad, 1H,
CH), 2.03 (s, 3H, CH3). Patent; Sivasankaran, Rajeev; Zimmermann, Kaspar; US2009/69315; (2009); (A1) English View in Reaxys Miyano; Abe; Journal of Organic Chemistry; vol. 36; (1971); p. 2948 View in Reaxys De Jongh et al.; Journal of Organic Chemistry; vol. 36; (1971); p. 3160,3167 View in Reaxys Khromov-Borisov; Tikhodeeva; Pharmaceutical Chemistry Journal; nb. 6; (1970); p. 320; Khimiko-Farmatsevticheskii Zhurnal; nb. 6; (1970); p. 18 View in Reaxys Bellec et al.; Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques; vol. 281; (1975); p. 885 View in Reaxys Bellec et al.; Journal of Heterocyclic Chemistry; vol. 16; (1979); p. 1611,1615 View in Reaxys Normant; Angelo; Bulletin de la Societe Chimique de France; (1960); p. 357 View in Reaxys Biniecki; Herold; Acta poloniae pharmaceutica; vol. 27; nb. 6; (1970); p. 529 - 532 View in Reaxys Patent; Bristol-Banyu Res.Inst.; US3360527; (1966); ; vol. 69; nb. 36117g; (1968) View in Reaxys Somasekhara et al.; Current Science; vol. 37; (1968); p. 669 View in Reaxys Patent; Tecnifax Corp.; US3558318; (1971); ; vol. 74; nb. 88683 View in Reaxys Ogata et al.; Tetrahedron; vol. 24; (1968); p. 1617,1620 View in Reaxys
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