5-(Bromomethyl)-1,3-benzodioxole [C8H7BrO2]

Query Query Br

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Date

12 reactions in Reaxys

2018-02-09 04h:57m:05s (EST)

O

1. Query O

Search as: As drawn

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HO

O

Br

O

O O

Rx-ID: 129624 View in Reaxys 1/12 Yield 100 %

Conditions & References Step-II (Preparation of benzyl bromides) General procedure: benzyl alcohols (1 mmol) in dry benzene (15 mL) and phosphorus tribromides (0.5 mL) and stirred at room temperature to get respective benzyl bromides in quantitative yields, usual work-up. With phosphorus tribromide in benzene, T= 20 °C Parihar, Swati; Kumar, Amit; Chaturvedi, Amit K.; Sachan, Naresh Kumar; Luqman, Suaib; Changkija, Bendangla; Manohar, Murli; Prakash, Om; Chanda; Khan, Feroz; Chanotiya; Shanker, Karuna; Dwivedi, Anila; Konwar, Rituraj; Negi, Arvind S.; Journal of Steroid Biochemistry and Molecular Biology; vol. 137; (2013); p. 332 344 View in Reaxys

97 %

8 :Carbon tetrabromide (3.8 g; 11.5 mmol) is added to 5-(methanol)-1,3-benzodioxole (1.5 g; 10 mmol) dissolved in dicholoromethane (30 ml); the mixture is cooled down to 0° C. Triphenylphosphine (3.0 g; 11.5 mmol) is added in portions, the solution is stirred for two hours at ambient temperature. The solvent is evaporated off and the solid obtained is purified by chromatography on a silica column (eluent: heptane/ethyl acetate: 3/1). The fractions are evaporated and the solid obtained is dried under vacuum (2.1 g; yield=97percent). NMR 1H (DMSO-d6, 400 MHz) δ: 7.02-6.98 (m, 1H, arom.); 6.96-6.93 (m, 1H, arom); 6.88-6.86 (m, 1H, arom); 6.02 (s, 2H, CH2); 4.66 (s, 2H, CH2). With carbon tetrabromide, triphenylphosphine in dichloromethane, Time= 2h, T= 0 - 20 °C Patent; Glacera Contour, Marie-Odile; Sidhu, Alban; Roubert, Pierre; Thurieau, Christophe; US2005/154039; (2005); (A1) English View in Reaxys

96 %

With phosphorus tribromide in diethyl ether, Time= 0.75h, T= 0 °C , Inert atmosphere Drew, Samuel L.; Lawrence, Andrew L.; Sherburn, Michael S.; Angewandte Chemie - International Edition; vol. 52; nb. 15; (2013); p. 4221 - 4224; Angew. Chem.; vol. 125; nb. 15; (2013); p. 4315 - 4318,4 View in Reaxys

95 %

With phosphorus tribromide in dichloromethane, Time= 3h, T= 0 - 20 °C Hu, Weimin; Qin, Hua; Cui, Yuxin; Jia, Yanxing; Chemistry - A European Journal; vol. 19; nb. 9; (2013); p. 3139 3147 View in Reaxys

93 %

With phosphorus tribromide Lienard, Philippe; Royer, Jacques; Quirion, Jean-Charles; Husson, Henri-Philippe; Tetrahedron Letters; vol. 32; nb. 22; (1991); p. 2489 - 2492 View in Reaxys

93 %

With sodium bromide, Time= 0.15h, Irradiation, microwave Kad, Goverdhan L.; Singh, Vasundhara; Kaur, Kanwal Preet; Singh, Jaswinder; Tetrahedron Letters; vol. 38; nb. 6; (1997); p. 1079 - 1080 View in Reaxys

91%

Synthesis of Compound 171 Synthesis of Compound 171 Preparation of piperonyl bromide: To a solution of piperonyl alcohol (5.0 g, 32.86 mmol) in anhydrous diethyl ether (80 mL) was added PBr3 (1.56 mL, 16.43 mmol) in one portion, and the resulting mixture was stirred at room temperature for 3 hours. The mixture was diluted with diethyl ether (100 mL) and washed with H2O (2*50 mL), saturated NaHCO3 (2*50 mL), and brine (2*50 mL). The ether layer was dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford piperonyl bromide (6.43 g, 91percent) as a yellow-grey solid.

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With phosphorus tribromide in diethyl ether Patent; Inflazyme Pharmaceuticals Ltd.; US2003/186943; (2003); (A1) English View in Reaxys Patent; Inflazyme Pharmaceuticals Ltd.; US6458829; (2002); (B1) English View in Reaxys 91%

Synthesis of Compound 171 Synthesis of Compound 171 Preparation of piperonyl bromide: To a solution of piperonyl alcohol (5.0 g, 32.86 mmol) in anhydrous diethyl ether (80 mL) was added PBr3 (1.56 mL, 16.43 mmol) in one portion, and the resulting mixture was stirred at room temperature for 3 hours. The mixture was diluted with diethyl ether (100 mL) and washed with H2O (2*50 mL), saturated NaHCO3 (2*50 mL), and brine (2*50 mL). The ether layer was dried over anhydrous MgSO4, and the solvent was removed under reduced pressure to afford piperonyl bromide (6.43 g, 91percent) as a yellow-grey solid. With phosphorus tribromide in diethyl ether Patent; Inflazyme Pharmaceuticals Ltd.; US6770658; (2004); (B2) English View in Reaxys

91 %

With phosphorus tribromide in dichloromethane, T= 0 - 20 °C Angle, Steven R.; Choi, Inchang; Tham, Fook S.; Journal of Organic Chemistry; vol. 73; nb. 16; (2008); p. 6268 6278 View in Reaxys

91 %

With functionalised triphenylphosphine monolith in dichloromethane, Time= 1h, Inert atmosphere Roper, Kimberley A.; Lange, Heiko; Polyzos, Anastasios; Berry, Malcolm B.; Baxendale, Ian R.; Ley, Steven V.; Beilstein Journal of Organic Chemistry; vol. 7; (2011); p. 1648 - 1655 View in Reaxys

90 %

Stage 1: With 1,2,3-Benzotriazole, thionyl chloride in dichloromethane Stage 2: With potassium bromide in dichloromethane, N,N-dimethyl-formamide, Time= 0.216667h Bandgar, Babasaheb P.; Bettigeri, Sampada V.; Monatshefte fur Chemie; vol. 135; nb. 10; (2004); p. 1251 - 1255 View in Reaxys

89 %

With carbon tetrabromide, triphenylphosphine Schaefer, Mark; Hanik, Nils; Kilbinger, Andreas F. M.; Macromolecules; vol. 45; nb. 17; (2012); p. 6807 - 6818 View in Reaxys

87 %

With phosphorus tribromide in dichloromethane, Time= 4h, T= 20 °C Wu, Deyan; Zhang, Tianhua; Chen, Yiping; Huang, Yadan; Geng, Haiju; Yu, Yanfa; Zhang, Chen; Lai, Zengwei; Wu, Yinuo; Guo, Xiaolei; Chen, Jianwen; Luo, Hai-Bin; Journal of Medicinal Chemistry; vol. 60; nb. 15; (2017); p. 6622 - 6637 View in Reaxys

86 %

With hydrogen bromide, T= 20 °C Harrowven, David C.; Nunn, Michael I.T.; Blumire, Nigel J.; Fenwick, David R.; Tetrahedron; vol. 57; nb. 20; (2001); p. 4447 - 4454 View in Reaxys

85 %

With hydrogen bromide, Time= 2h, Ambient temperature Beard, Andrew R.; Hazell, Sarah J.; Mann, John; Palmer, Christopher; Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999); nb. 11; (1993); p. 1235 - 1238 View in Reaxys

84 %

With phosphorus tribromide in tetrahydrofuran, T= 0 °C , Inert atmosphere

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Yu, Wing-Yiu; Tsoi, Yuk-Tai; Zhou, Zhongyuan; Chan, Albert S. C.; Organic Letters; vol. 11; nb. 2; (2009); p. 469 - 472 View in Reaxys 83 %

With phosphorus tribromide Hirano; Osawa; Yamaoka; Yokoi; Biological and Pharmaceutical Bulletin; vol. 24; nb. 11; (2001); p. 1277 - 1281 View in Reaxys

82 %

With carbon tetrabromide, triphenylphosphine in benzene, Time= 3h, T= 0 - 20 °C , Inert atmosphere Pelletier, Guillaume; Lie, Sharon; Mousseau, James J.; Charette, Andre B.; Organic Letters; vol. 14; nb. 21; (2012); p. 5464 - 5467,4 View in Reaxys Pelletier, Guillaume; Lie, Sharon; Mousseau, James J.; Charette, Andre B.; Organic Letters; vol. 14; nb. 21; (2012); p. 5464 - 5467 View in Reaxys

78 %

With phosphorus tribromide, triethylamine in tetrachloromethane Mitra, Jayati; Mitra, Alok Kumar; Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry; vol. 33; nb. 10; (1994); p. 953 - 956 View in Reaxys

70 %

With phosphorus tribromide in diethyl ether, Time= 0.166667h, T= 0 °C Imperio, Daniela; Pirali, Tracey; Galli, Ubaldina; Pagliai, Francesca; Cafici, Laura; Canonico, Pier Luigi; Sorba, Giovanni; Genazzani, Armando A.; Tron, Gian Cesare; Bioorganic and Medicinal Chemistry; vol. 15; nb. 21; (2007); p. 6748 - 6757 View in Reaxys

67 %

With phosphorus tribromide in toluene, T= 0 - 20 °C Aslam, Shazia N.; Stevenson, Philip C.; Phythian, Sara J.; Veitch, Nigel C.; Hall, David R.; Tetrahedron; vol. 62; nb. 17; (2006); p. 4214 - 4226 View in Reaxys With hydrogen bromide, T= 0 °C Robinsin,G. M.; Robinson,R.; Journal of the Chemical Society; vol. 105; (1914); p. 1463 View in Reaxys With hydrogen bromide Karrer et al.; Helvetica Chimica Acta; vol. 6; (1923); p. 914 View in Reaxys Burrows; Turner; Journal of the Chemical Society; vol. 119; (1921); p. 434 View in Reaxys With hydrogen bromide in benzene, Time= 0.166667h Boger, Dale L.; Brotherton, Christine E.; Kelley, Marshall D.; Tetrahedron; vol. 37; nb. 23; (1981); p. 3977 - 3980 View in Reaxys

4.0 g

With hydrogen bromide in benzene, Time= 2h, Ambient temperature Asakawa, Yoshinori; Takikawa, Keiko; Tori, Motoo; Phytochemistry (Elsevier); vol. 26; nb. 4; (1987); p. 1023 1026 View in Reaxys

3.77 g

With hydrogen bromide in benzene, Time= 2h, Ambient temperature Asakawa, Yoshinori; Matsuda, Reiko; Cheminat, Annie; Phytochemistry (Elsevier); vol. 26; nb. 4; (1987); p. 1117 - 1122 View in Reaxys With phosphorus tribromide in diethyl ether, Time= 3h, Ambient temperature, Yield given

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Van Oeveren; Jansen; Feringa; Journal of Organic Chemistry; vol. 59; nb. 20; (1994); p. 5999 - 6007 View in Reaxys With carbon tetrabromide, triphenylphosphine in dichloromethane, Time= 2h, reflux, Substitution Nishiwaki, Hisashi; Nakagawa, Yoshiaki; Takeda, David Y.; Okazawa, Atsushi; Akamatsu, Miki; Miyagawa, Hisashi; Ueno, Tamio; Nishimura, Keiichiro; Pest Management Science; vol. 56; nb. 10; (2000); p. 875 - 881 View in Reaxys With carbon tetrabromide, triphenylphosphine in dichloromethane Vanotti, Ermes; Bargiotti, Alberto; Biancardi, Roberto; Pinciroli, Vittorio; Ermoli, Antonella; Menichincheri, Maria; Tibolla, Marcello; Tetrahedron; vol. 58; nb. 17; (2002); p. 3361 - 3370 View in Reaxys 3.C :(2S,3R)-3-(2-(benzo[d] [l,3]dioxol-5-yl)ethyl)-4-oxo-l- (phenylcarbamoyl)azetidine-2-carboxylic acid (35): Compound 35 was synthesized by general method A (step 1) using 5-(2-bromoethyl)benzo[d][l,3] dioxole as the electrophile instead of 4-bromomethyl-2-bis-Boc-aminopyridine. The starting 5- (bromomethyl)benzo[<f][l,3]dioxole was made by standard treatment of benzo[cT][l,3]dioxol- 5-ylmethanol with carbon tetrabromide and triphenylphosphine in toluene. The synthesis was then completed by following general method C. With carbon tetrabromide, triphenylphosphine in toluene Patent; DAIAMED, INC.; WO2006/108039; (2006); (A2) English View in Reaxys With hydrogen bromide in toluene, Time= 0.5h, T= 20 °C Ceccarelli, Roberto; Insogna, Susanna; Bella, Marco; Organic and Biomolecular Chemistry; vol. 4; nb. 23; (2006); p. 4281 - 4284 View in Reaxys With phosphorus tribromide in dichloromethane, T= 0 - 20 °C Qin, Hua; Xu, Zhengren; Cui, Yuxin; Jia, Yanxing; Angewandte Chemie - International Edition; vol. 50; nb. 19; (2011); p. 4447 - 4449 View in Reaxys With phosphorus tribromide in dichloromethane, Time= 1.33333h, T= -5 - 20 °C Taylor, Laura L.; Goldberg, Frederick W.; Hii, King Kuok Mimi; Organic and Biomolecular Chemistry; vol. 10; nb. 22; (2012); p. 4424 - 4432 View in Reaxys General procedure for the preparation of 4-aminomethyl-3-(substituted benzyloxyimino)pyrrolidine dimesylates (8a-w) General procedure: To a solution of phenylmethanols 5a-w (5 mmol) dissolved in methylene chloride (50 mL) in an ice-water bath was added phosphorus tribromide (5.5 mmol), and the mixture was stirred at the same temperature for 30 min. The mixture was washed with cool water, dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield (bromomethyl)benzenes 6aew as offwhite solids or light yellow oils With phosphorus tribromide in dichloromethane, Time= 0.5h, T= 0 °C Feng, Lianshun; Lv, Kai; Liu, Mingliang; Wang, Shuo; Zhao, Jing; You, Xuefu; Li, Sujie; Cao, Jue; Guo, Huiyuan; European Journal of Medicinal Chemistry; vol. 55; (2012); p. 125 - 136 View in Reaxys General procedure: crude product 2a which was then dissolved in anhydrous methylene chloride (50 mL) and cooled to 0–5 ºC by ice bath. To this solution was added dropwise phosphorus tribromide (0.5 mL, 5 mmol) over a period of 15 min and stirred for 0.5 h at the same temperature, and then washed with saturated brine (3 Χ 15 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude compound 3a. With phosphorus tribromide in dichloromethane, Time= 0.75h, T= 0 - 5 °C

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Tynebor, Robert M.; Chen, Meng-Hsin; Natarajan, Swaminathan R.; O'Neill, Edward A.; Thompson, James E.; Fitzgerald, Catherine E.; O'Keefe, Stephen J.; Doherty, James B.; Bioorganic and Medicinal Chemistry Letters; vol. 22; nb. 18; (2012); p. 5971 - 5975 View in Reaxys General procedure for preparation of benzyl bromides from benzaldehydes: General procedure: General procedure for preparation of benzyl bromides from benzaldehydes: To a stirring solution of aldehyde (1.0 equiv) in methanol (0.2 M) was added sodium borohydride (2.0 equiv.). The resulting solution was stirred at RT for 30-60 mins, until no precipitate was evident in solution and flask was cool to the touch. Solvent was removed in vacuo and dichloromethane introduced. Organic layer was washed using water, dried over sodium sulfate, filtered and solvent removed in vacuo to yield crudebenzyl alcohol, which was used without further purification. To a stirring solution of benzyl alcohol (1.0 equiv.) in dry dichloromethane (0.1 M) at 0 °C was added phosphorus tribromide (1.1 equiv.). The reaction solution was stirred at 0 00 for 30 mins, quenched with water, transferred to a separating funnel and the organic layer washed with water. Combined organic layers were dried over sodium sulfate, filteredand solvent removed in vacuo to yield crude benzyl bromide, which was used without purification in catalytic Wittig reactions. o Br 5-(Bromomethyl)-1,3-benzodioxole was prepared inaccordance with the general procedure. 1,3-Benzodioxol-5-o - ylmethanol was prepared in 88percent yield (2.68 g, 17.6 mmol) fromthe reaction of piperonal (3.00 g, 20 mmol, 1 .0 equiv.) and sodium borohydride (1 .51 g,40 mmol, 2.0 equiv.). Upon reaction with phosphorus tribromide (1.82 mL, 19.4 mmol,1.1 equiv.), 5-(bromometh/l)-1,3-benzodioxole was obtained as a white solid in 85percentyield (3.54 g, 16.5 mmol). H NMR (400 MHz, CDCI3) 6: 3.84 (s, 3H), 3.87 (s, 6H), 4.47(s, 2H), 6.62 (s, 2H). With phosphorus tribromide in dichloromethane, Time= 0.5h, T= 0 °C , Schlenk technique, Inert atmosphere Patent; DUBLIN CITY UNIVERSITY; O'BRIEN, Christopher; WO2014/140353; (2014); (A1) English View in Reaxys With phosphorus tribromide Sathish Kumar; Kumar, Amit; Singh, Jyotsna; Hasanain, Mohammad; Singh, Arjun; Fatima, Kaneez; Yadav, Dharmendra K.; Shukla, Vinay; Luqman, Suaib; Khan, Feroz; Chanda, Debabrata; Sarkar, Jayanta; Konwar, Rituraj; Dwivedi, Anila; Negi, Arvind S.; European Journal of Medicinal Chemistry; vol. 86; (2014); p. 740 - 751 View in Reaxys With phosphorus tribromide in dichloromethane, Time= 0.5h, T= 0 °C , Inert atmosphere, Schlenk technique Coyle, Emma E.; Doonan, Bryan J.; Holohan, Andrew J.; Walsh, Killian A.; Lavigne, Florie; Krenske, Elizabeth H.; O'Brien, Christopher J.; Angewandte Chemie - International Edition; vol. 53; nb. 47; (2014); p. 12907 12911; Angew. Chem.; vol. 126; nb. 47; (2014); p. 13121 - 13125,5 View in Reaxys Benzo[1,3]dioxol-5-ylmethyl-triphenyl-phosphonium bromide (10). To a solution of the piperonyl alcohol (8) (2.0 g, 13.15 mmol) in anhydrous CH2Cl2 (30 mL), cooled to 0 °C and stirred, under an argon atmosphere, freshly distilled PBr3 (3.7 mL, 39.45 mmol), was added dropwise. The resulting solution was kept under stirring at 0 °C for a further 20 minutes. After, the ice bath was removed, maintaining the stirring for a further 2 h. The system was cooled again to 0 °C and a saturated solution of NaHCO3 (75 mL) was slowly added. Extraction was carried out with ethyl ether (3x 70 mL). The combined organic phases were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure to afford crude bromide (9). This bromide (used immediately after its preparation) was solubilized with anhydrous acetonitrile (30 mL), treated with triphenylphosphine (3.45 g, 13.15 mmol) and stirred overnight, under reflux. Acetonitrile was removed under reduced pressure and the residue was recrystallized from ethanol to provide (5.21 g) Wittig salt (10) in 83percent overall yield. Rf 0.53 (CH2Cl2/MeOH 9:1). mp: 237.2-238.5 °C. IR (neat) νmax/cm-1: 3018, 1492, 1438, 1246, 1109, 750, 687. 1H

NMR (400 MHz, CDCl3) δ 7.80-7.62 (m, 15H), 6.62-6.59 (m, 1H), 6.53 (d, 2H, J=5.5 Hz), 5.87 (s, 2H), 5.28 (d,

2H, J=13.9 Hz). 13C NMR (100 MHz, CDCl3) δ 147.6, 134.9 (d, J=11.5 Hz), 134.2 (d, J=38.6 Hz), 130.0 (d, J=49.7 Hz), 125.3, 119.9 (d, J=36 Hz), 118.0, 117.2, 111.2 (d, J=18.4 Hz), 108.4 (d, J=13.5 Hz), 101.1, 30.4 (d, J=187.4 Hz). HRMS (ESI+) calcd for C26H22BrO2P [M-HBr]+ 397.1352, found 397.1358. With phosphorus tribromide in dichloromethane, Time= 2.33333h, T= 0 - 20 °C , Inert atmosphere Diaz-Muñoz, Gaspar; Isidorio, Raquel Geralda; Miranda, Izabel Luzia; de Souza Dias, Gabriel Nunes; Diaz, Marisa Alves Nogueira; Tetrahedron Letters; vol. 58; nb. 33; (2017); p. 3311 - 3315 View in Reaxys

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6 :Piperonyl alcohol (compound g) (1 g, 1 eq), dichloromethane (15 ml), and pyridine (1 eq) were introduced into an eggplant-shaped flask and ice-cooled. Phosphorus tribromide (0.5 eq) was slowly added thereto. Five minutes later, the mixture was adjusted to room temperature and stirred for 2 hours. Water was added to terminate the reaction, followed by extraction with dichloromethane. Subsequently, the extract was washed with saturated saline, dehydrated with sodium sulfate, and concentrated. Thus, the compound h was obtained. The obtained compound was directly used for the next reaction. With pyridine, phosphorus tribromide in dichloromethane, Time= 2h, T= 20 °C , Cooling with ice Patent; RIKEN; Nakano, Takeshi; ASAMI, Tadao; OSADA, Hiroyuki; (31 pag.); US2017/305886; (2017); (A1) English View in Reaxys

O

Br

O

O O

Rx-ID: 34125316 View in Reaxys 2/12 Yield

Conditions & References Reaction Steps: 2 1: sodium tetrahydroborate / dichloromethane / 0.5 h / 20 °C 2: phosphorus tribromide / dichloromethane / 0.5 h / 0 °C With sodium tetrahydroborate, phosphorus tribromide in dichloromethane Feng, Lianshun; Lv, Kai; Liu, Mingliang; Wang, Shuo; Zhao, Jing; You, Xuefu; Li, Sujie; Cao, Jue; Guo, Huiyuan; European Journal of Medicinal Chemistry; vol. 55; (2012); p. 125 - 136 View in Reaxys Reaction Steps: 2 1: sodium tetrahydroborate / methanol / 1 h / 20 °C 2: phosphorus tribromide / benzene / 20 °C With sodium tetrahydroborate, phosphorus tribromide in methanol, benzene Parihar, Swati; Kumar, Amit; Chaturvedi, Amit K.; Sachan, Naresh Kumar; Luqman, Suaib; Changkija, Bendangla; Manohar, Murli; Prakash, Om; Chanda; Khan, Feroz; Chanotiya; Shanker, Karuna; Dwivedi, Anila; Konwar, Rituraj; Negi, Arvind S.; Journal of Steroid Biochemistry and Molecular Biology; vol. 137; (2013); p. 332 344 View in Reaxys Reaction Steps: 2 1: sodium tetrahydroborate; methanol / 20 °C / Schlenk technique; Inert atmosphere 2: phosphorus tribromide / dichloromethane / 0.5 h / 0 °C / Schlenk technique; Inert atmosphere With methanol, sodium tetrahydroborate, phosphorus tribromide in dichloromethane Patent; DUBLIN CITY UNIVERSITY; O'BRIEN, Christopher; WO2014/140353; (2014); (A1) English View in Reaxys Reaction Steps: 2 1: sodium tetrahydroborate / methanol 2: phosphorus tribromide With sodium tetrahydroborate, phosphorus tribromide in methanol Sathish Kumar; Kumar, Amit; Singh, Jyotsna; Hasanain, Mohammad; Singh, Arjun; Fatima, Kaneez; Yadav, Dharmendra K.; Shukla, Vinay; Luqman, Suaib; Khan, Feroz; Chanda, Debabrata; Sarkar, Jayanta; Konwar, Rituraj; Dwivedi, Anila; Negi, Arvind S.; European Journal of Medicinal Chemistry; vol. 86; (2014); p. 740 - 751 View in Reaxys Reaction Steps: 2 1: sodium tetrahydroborate / methanol / 20 °C / Inert atmosphere; Schlenk technique 2: phosphorus tribromide / dichloromethane / 0.5 h / 0 °C / Inert atmosphere; Schlenk technique With sodium tetrahydroborate, phosphorus tribromide in methanol, dichloromethane

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Coyle, Emma E.; Doonan, Bryan J.; Holohan, Andrew J.; Walsh, Killian A.; Lavigne, Florie; Krenske, Elizabeth H.; O'Brien, Christopher J.; Angewandte Chemie - International Edition; vol. 53; nb. 47; (2014); p. 12907 12911; Angew. Chem.; vol. 126; nb. 47; (2014); p. 13121 - 13125,5 View in Reaxys Stage 1: With sodium tetrahydroborate in methanol, T= 0 °C Stage 2: With phosphorus tribromide in dichloromethane, T= 0 °C Li, Wei; Yang, Chao; Gao, Guo-Lin; Xia, Wujiong; Synlett; vol. 27; nb. 9; (2016); p. 1391 - 1396; Art.No: ST-2015W0902-L View in Reaxys Stage 1: With sodium tetrahydroborate in ethanol, Time= 1h, T= 20 °C Stage 2: With phosphorus tribromide, Time= 1h, T= 20 °C Wu, Xi-Shan; Wang, Rui; Xing, Yan-Li; Xue, Xiao-Qian; Zhang, Yan; Lu, Yong-Zhi; Song, Yu; Luo, Xiao-Yu; Wu, Chun; Zhou, Yu-Lai; Jiang, Jian-Qin; Xu, Yong; Acta Pharmacologica Sinica; vol. 37; nb. 11; (2016); p. 1516 - 1524 View in Reaxys

O

Br

O

Rx-ID: 25118968 View in Reaxys 3/12 Yield 90%

Conditions & References 1 : EXAMPLE 1 Then, 0.6 mol of the thus-obtained compound (VI-1) and 0.006 mol of benzoyl peroxide were dissolved in a 3.5-fold amount by weight, based on (VI-1), of carbon tetrachloride, and 0.66 mol of bromine gas was blown thereinto under reflux condition. The blowing time was 10 hours. After completion of the reaction, the solvent was distilled off to obtain 3,4-methylenedioxybenzyl bromide (VII-1) in 90percent yield. With bromine, dibenzoyl peroxide Patent; Sumitomo Chemical Company, Limited; US4335263; (1982); (A1) English View in Reaxys With N-Bromosuccinimide, 2,2'-azobis(isobutyronitrile) in tetrachloromethane, Time= 12h, Inert atmosphere, Reflux Tuley, Alfred; Wang, Yane-Shih; Fang, Xinqiang; Kurra, Yadagiri; Rezenom, Yohannes H.; Liu, Wenshe R.; Chemical Communications; vol. 50; nb. 20; (2014); p. 2673 - 2675 View in Reaxys

Br

HO HO

O O

Rx-ID: 37293586 View in Reaxys 4/12 Yield

Conditions & References Reaction Steps: 2 1: caesium carbonate / acetonitrile / 4 h / Reflux 2: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 12 h / Inert atmosphere; Reflux With N-Bromosuccinimide, 2,2'-azobis(isobutyronitrile), caesium carbonate in tetrachloromethane, acetonitrile Tuley, Alfred; Wang, Yane-Shih; Fang, Xinqiang; Kurra, Yadagiri; Rezenom, Yohannes H.; Liu, Wenshe R.; Chemical Communications; vol. 50; nb. 20; (2014); p. 2673 - 2675 View in Reaxys

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2H

OH

2H

O

2H

Br

2H

Rx-ID: 34960517 View in Reaxys 5/12 Yield

Conditions & References

95 %

With phosphorus tribromide in dichloromethane, Time= 3h, T= 0 - 20 °C Hu, Weimin; Qin, Hua; Cui, Yuxin; Jia, Yanxing; Chemistry - A European Journal; vol. 19; nb. 9; (2013); p. 3139 3147 View in Reaxys

H

HO

H

14C 2

O

Br

14C 2

O O

O

Rx-ID: 9897451 View in Reaxys 6/12 Yield

Conditions & References With hydrogen bromide in water, Time= 1h, T= 20 °C Ray, Tapan; Ciszewska, Grazyna; Allentoff, Alban J.; Wu, Amy; Jones, Lawrence; Journal of Labelled Compounds and Radiopharmaceuticals; vol. 47; nb. 14; (2004); p. 1029 - 1033 View in Reaxys

Br

O O

Rx-ID: 5435333 View in Reaxys 7/12 Yield

Conditions & References MAMALIS; GREEN; OUTRED; RIX; Journal of the Chemical Society; vol. 65; (1965); p. 1829 - 1843 View in Reaxys Weinstein,B.; Craig,A.R.; Journal of Organic Chemistry; vol. 41; nb. 5; (1976); p. 875 - 878 View in Reaxys 14 : 1-(3,4-Methylenedioxybenzylthio)-4-Phenylphthalazine EXAMPLE 14 1-(3,4-Methylenedioxybenzylthio)-4-Phenylphthalazine When 3,4-methylenedioxy benzylbromide (80 mg; 0.37 mmol) is used in the procedure described in Example 4 instead of 3-chlorobenzyl bromide, 1-(3,4-methylenedioxybenzylthio)-4-phenylphthalazine is obtained as a white solid after stirring the mixture for two days at room temperature (R1=3,4-methylendioxyphenyl, R2=phenyl, A=benzene, Y1=CH2, m=0, n=1, p=0, q=0). Patent; Cell Pathways, Inc.; US6486158; (2002); (B1) English View in Reaxys 4.A : A. A. piperonyl bromide Piperonol, 30.4 g. (0.2 mole) was added in small portions to 200 ml. of 48percent hydrobromic acid at 0°C. When all had been added, the reaction mixture was diluted with 200 ml. of water and stirred for an additional 30 minutes. Then 200 ml. of dichloromethane was added. The layers were separated, the organic layer was washed with water and dried over magnesium sulfate. The solvent was removed by evaporation under reduced pressure to give 38.5 g. of piperonyl bromide. Patent; Chevron Research Company; US3941884; (1976); (A1) English View in Reaxys

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O

HO

O

HBr

O

Br

O

Rx-ID: 5435335 View in Reaxys 8/12 Yield 93 %

Conditions & References in benzene, T= 5 - 20 °C Rotherham, Lloyd W.; Edward Semple; Journal of Organic Chemistry; vol. 63; nb. 19; (1998); p. 6667 - 6672 View in Reaxys

p-nitropiperonal

K18 F

O

Br

O Br O

O

F

Rx-ID: 24433883 View in Reaxys 9/12 Yield

Conditions & References 3 : Synthesis of NCA 6-[18 F]Piperonyl Bromide (5) EXAMPLE 3 Synthesis of NCA 6-[18 F]Piperonyl Bromide (5) The K18 F/kryptofix 222 was prepared as described in Example 1. A solution of p-nitropiperonal 4 (10 mg) in 0.3 mL of dry DMSO was added to the dried K18 F/kryptofix 222. The mixture was stirred at 120° for 5 minutes, cooled in an ice bath, and then 0.2 mL of 1M lithium aluminum hydride in diethyl ether was added. The resulting mixture was stirred at room temperature for 10 minutes, cooled in an ice bath, and then 1 mL of saturated NaCl(aq) was added. After the mixture was extracted with ether (3*1 mL), the combined extracts were dried by passing through K2 CO3 and concentrated to give approximately 1 mL solution. Pyridine (0.04 mL) and thionyl bromide (0.04 mL) were added sequentially. The reaction mixture was stirred at room temperature for 5 minutes, then diluted with 1 mL of ice water and extracted with ether (2*1 mL). The combined ether layers were dried by passing through K2 CO3. The solvent was then evaporated and the residue taken up in 0.3 mL of dry THF. The solution of 6-[18 F]piperonyl bromide 5 was analyzed by thin layer chromatography (silica, 7:3 hexane:ethyl acetate; 6-[18 F]piperonyl alcohol RF =0.24, 6-[18 F]piperonyl bromide RF =0.68). The labeled bromide was used for the alkylation step without further purification. With pyridine, dibromo sulfoxide in tetrahydrofuran, (2S)-N-methyl-1-phenylpropan-2-amine hydrate, diethyl ether, dimethyl sulfoxide Patent; The United States of America as represented by the Department of Energy; US5254726; (1993); (A1) English View in Reaxys

N–

[(+)-2-Hydroxypipanyl-3-idene]glycine ethyl ester

Li+

O Br O

F

Br

O O

Rx-ID: 24437739 View in Reaxys 10/12 Yield

Conditions & References 4 : Alkylation of the Schiff Base (2) with 6-[18 F]Piperonyl Bromide (5) EXAMPLE 4 Alkylation of the Schiff Base (2) with 6-[18 F]Piperonyl Bromide (5) [(+)-2-Hydroxypipanyl-3-idene]glycine ethyl ester 3 (25-50 mg, 9.8-19.7*10-5 mol) and 2,2,6,6-tetramethyl-piperidyllithium (2.4-4.9*10-4 mol) in THF, total volume 0.6-0.8 mL, was cooled to -78° C. with dry ice/acetone. The solution of crude 6-[18 F]piperonyl bromide 5 in THF was then added to the mixture of the Schiff base anion freshly prepared as described in Example 3. The resulting mixture was stirred for 15 minutes at 78° C., and the solution of crude product was analyzed by TLC (silica gel, 6:4 hexane:ethyl acetate). The alkylation product was deprotected without isolation.

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in tetrahydrofuran Patent; The United States of America as represented by the Department of Energy; US5254726; (1993); (A1) English View in Reaxys

O

Br

O

Rx-ID: 2331334 View in Reaxys 11/12 Yield 84 %

Conditions & References With boron trifluoride diethyl etherate, bromocatecholborane in dichloromethane, Time= 0.0333333h, Ambient temperature King, Patrick F.; Stroud, Stephen G.; Tetrahedron Letters; vol. 26; nb. 11; (1985); p. 1415 - 1418 View in Reaxys

HO

O

Br

H

Br

O

O O

Rx-ID: 5435334 View in Reaxys 12/12 Yield

Conditions & References Robinsin,G. M.; Robinson,R.; Journal of the Chemical Society; vol. 105; (1914); p. 1463 View in Reaxys

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