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8 reactions in Reaxys
2016-05-20 11h:36m:12s (EST)
Cl N
1. Query
NH
Search as: As drawn
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Cl
H N
Cl
Cl
N
N H
N H
Rx-ID: 9177100 View in Reaxys 1/8 Yield
Conditions & References
74 %
5.1.3. General procedure for the synthesis of various substituted benzylpiperazines (3a-s) General procedure: Anhydrous piperazine (6.89 g, 80 mmol) was dissolved in 40 mL of freshly distilled THF. Once the piperazine was fully dissolved, 2.303 mL (20 mmol) of benzyl chloride was added dropwise. The reaction mixture was then refluxed for about 4 h until benzyl chloride disappeared, as assessed by TLC. The stirring mixture was allowed to cool, and then filtered. The filtrate was concentrated in a rotary evaporator and then diluted with EtOAc (100 mL) and water (50 mL), which was then made basic (pH>12) with a saturated 1 N NaOH aqueous solution and separated. The organic phase was washed with water (4 .x. 100 mL), brine (2 .x. 100 mL), dried over Na2SO4 and concentrated to yield an oil. Column chromatography (PE/EtOAc = 1:1 to EtOAc/MeOH = 5:1) afforded a pale yellow liquid. in tetrahydrofuran, Time= 4h, Reflux Zhang, Cunlong; Tan, Chunyan; Zu, Xuyu; Zhai, Xin; Liu, Feng; Chu, Bizhu; Ma, Xiaohua; Chen, Yuzong; Gong, Ping; Jiang, Yuyang; European Journal of Medicinal Chemistry; vol. 46; nb. 4; (2011); p. 1404 - 1414 View in Reaxys
73 %
in toluene, Time= 2h, T= 85 °C Capuano, Ben; Crosby, Ian T.; Lloyd, Edward J.; Taylor, David A.; Australian Journal of Chemistry; vol. 55; nb. 9; (2002); p. 565 - 576 View in Reaxys With triethylamine in ethanol, Time= 12h, T= 55 °C Cai, Mingyi; Li, Zhong; Fan, Feng; Huang, Qingchun; Shao, Xusheng; Song, Gonghua; Journal of Agricultural and Food Chemistry; vol. 58; nb. 5; (2010); p. 2624 - 2629 View in Reaxys in acetonitrile, T= 20 °C Ren, Yu; Zhang, Hui Zhen; Zhang, Shao Lin; Luo, Yun Lei; Zhang, Ling; Zhou, Cheng He; Geng, Rong Xia; Journal of Chemical Sciences; vol. 127; nb. 12; (2015); p. 2251 - 2260 View in Reaxys
O
Cl
O N
N
N
N H Cl
Rx-ID: 5025237 View in Reaxys 2/8 Yield
Conditions & References With trifluoroacetic acid in dichloromethane, Ambient temperature Bourrain, Sylvie; Collins, Ian; Neduvelil, Joseph G.; Rowley, Michael; Leeson, Paul D.; Patel, Smita; Patel, Shil; Emms, Frances; Marwood, Rosemarie; Chapman, Kerry L.; Fletcher, Alan E.; Showell, Graham A.; Bioorganic and Medicinal Chemistry; vol. 6; nb. 10; (1998); p. 1731 - 1743 View in Reaxys 4.1.2 General procedure for the synthesis of 1-(3-substituted benzyl)piperazines 4a–g
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General procedure: These compounds were prepared by means of the previously reported methods [44]. To a solution of tert-butyl piperazine-1-carboxylate (0.559g, 3.0mmol) and triethylamine (0.63mL, 3.3mmol) in CH2Cl2 (15mL) appropriate substituted benzyl chlorides or benzyl bromides 2a–g (3.6mmol) were added. After stirring the mixture at room temperature overnight, it was then diluted with H2O and the organics extracted with CH2Cl2 (2×20mL), dried over MgSO4, and concentrated under reduced pressure. Purification of the crude material by flash column chromatography (SiO2, PE/AcOEt, 60/40) gave the corresponding intermediates. These intermediates (2.49mmol) were then treated with TFA (5.75mL, 76.8mmol) in toluene (15mL) and stirred for 80min at room temperature. After the removal of the solvent under reduced pressure, the residue was diluted with aqueous NaOH (1N) and the organics extracted with CH2Cl2 (2×20mL), dried over MgSO4, and concentrated under reduced pressure to give the desired compounds 4a–g (72–89percent). With trifluoroacetic acid in toluene, Time= 1.33333h, T= 20 °C Sadeghzadeh, Masoud; Sheibani, Shahab; Ghandi, Mehdi; Daha, Fariba Johari; Amanlou, Massoud; Arjmand, Mohammad; Hasani Bozcheloie, Abolfazl; European Journal of Medicinal Chemistry; vol. 64; (2013); p. 488 - 497 View in Reaxys Cl
Cl
Br
N
N H
Rx-ID: 24650669 View in Reaxys 3/8 Yield
Conditions & References 14.A : Step A Step A 1-(3-Chlorobenzyl)-piperazine The title compound was obtained following the procedure described in Steps 4a-b using 3-chlorobenzyl bromide instead of 4-chlorobenzyl chloride in Step 4a. 1 H NMR (360 MHz, CDCl3) δ 2.60-2.72 (4H, m), 3.03-3.14 (4H, m), 3.65 (2H, s), 7.16-7.44 (4H, m). Patent; Merck, Sharp and Dohme, Ltd.; US5684006; (1997); (A1) English View in Reaxys
O
Cl
O
2 HCl
N
N
Cl
H
N
N H Cl
Rx-ID: 8596970 View in Reaxys 4/8 Yield 67 %
Conditions & References With hydrogenchloride, Time= 18h, Heating, Decarboxylation, hydrolysis Radl, Stanislav; Hezky, Petr; Proska, Jan; Hejnova, Lucie; Krejci, Ivan; Archiv der Pharmazie; vol. 333; nb. 5; (2000); p. 107 - 112 View in Reaxys
Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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Cl
Cl
Cl
N
N H
Rx-ID: 16713987 View in Reaxys 5/8 Yield
Conditions & References Reaction Steps: 2 1: K2CO3 / ethanol / Heating 2: TFA / CH2Cl2 / Ambient temperature With potassium carbonate, trifluoroacetic acid in ethanol, dichloromethane Bourrain, Sylvie; Collins, Ian; Neduvelil, Joseph G.; Rowley, Michael; Leeson, Paul D.; Patel, Smita; Patel, Shil; Emms, Frances; Marwood, Rosemarie; Chapman, Kerry L.; Fletcher, Alan E.; Showell, Graham A.; Bioorganic and Medicinal Chemistry; vol. 6; nb. 10; (1998); p. 1731 - 1743 View in Reaxys
Cl
Cl
HCl N
N
N H
N H
Rx-ID: 35483119 View in Reaxys 6/8 Yield
Conditions & References With sodium hydroxide in water Zeng, Xiaoyun; Zheng, Jinhong; Fu, Chenglai; Su, Hang; Sun, Xiaoli; Zhang, Xuesi; Hou, Yingjian; Zhu, Yi; Molecular Pharmacology; vol. 83; nb. 5; (2013); p. 1099 - 1108 View in Reaxys Cl
H N
Br
Cl N
N H
N H
Rx-ID: 31795370 View in Reaxys 7/8 Yield
Conditions & References Chai, Yunfeng; Jiang, Kezhi; Sun, Cuirong; Pan, Yuanjiang; Chemistry - A European Journal; vol. 17; nb. 39; (2011); p. 10820 - 10824 View in Reaxys Cl
N
N H
Rx-ID: 5935834 View in Reaxys 8/8 Yield 65 %
Conditions & References 2 : General Procedure A: Synthesis of 1-benzylpiperazines. General procedure: General Procedure A: Synthesis of 1-benzylpiperazines.[0088]Anhydrous piperazine (6.0 equiv.) was suspended in THF (0.45 M benzyl halide). The mixture was heated to reflux until piperazine fully dissolved. Upon dissolution, the substituted benzyl halide (1.0 equiv.) was added to the reaction mixture. A white solid immedi-
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ately formed. The reaction mixture was stirred at reflux for 2.5 hours. The mixture was cooled to room temperature. The solid was filtered and washed with THF and EtOAc. The combined filtrates were concentrated to 10percent of the original volume. The concentrate was poured into a separatory funnel with 5percent brine/H2O made basic (pH>12) with KOH. The aqueous layer was extracted with DCM and EtOAc. The organic layers were combined, dried over Na2SO4, and concentrated. The crude product was purified by silica gel column chromatography to yield pure 1-benzylpiperazine in tetrahydrofuran, Time= 2.5h, Reflux Patent; The Board of Trustees of the University lllinois; HERGENROTHER, Paul J.; US2013/96133; (2013); (A1) English View in Reaxys Protiva; Rajsner; Trcka; et al.; Collection of Czechoslovak Chemical Communications; vol. 40; nb. 12; (1975); p. 3904 - 3923 View in Reaxys Ikeda; Yakugaku Zasshi; vol. 89; (1969); p. 677,685; ; vol. 71; nb. 61339; (1969) View in Reaxys Oakwood Products, Inc., 1741 Old Dunbar Road, West Columbia, S.C. 29172, USA. TCI America, 9211 N. Harborgate Street, Portland, Oreg. 97203, USA ... 1-(4-bromobenzyl)piperazine; 1-(4-bromo-2-fluorobenzyl)piperazine; 1-(4-tert-butylbenzyl)piperazine; 1-(2-chlorobenzyl)piperazine; 1-(3-chlorobenzyl)piperazine; 1-(4-chlorobenzyl)piperazine; 1-(2-chloro-benzyl)-piperazine hydrochloride; 1-(4-chloro-benzyl)-piperazine hydrochloride; ... Patent; Gillespie, Paul; Goodnow, JR., Robert Alan; Erickson, Shawn David; Jones, Richard; US2009/149466; (2009); (A1) English View in Reaxys
Copyright © 2016 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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