诺卜醇的催化转移氢化反应

化学试剂,2007,29(10),640

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诺卜醇的催化转移氢化反应

张磊,薛忠辉,陈国良*

(沈阳药科大学制药工程学院,辽宁沈阳 110016)

中图分类号:O624 文献标识码:B 文章编号:0258-3283(2007)10-0640-01

匹维溴铵(pinaverium bromide)是一种选择性胃肠道钙离子拮抗剂,用于治疗肠易激综合症,效果良好,不良反应轻微。匹维溴铵是以诺卜醇为起始原料,经催化氢化等多步反应制得,其中将诺卜醇催化氢化为二氢诺卜醇(1)的反应,是以雷尼镍为催化剂,乙醇为溶剂,在高温高压下进行。我们通过实验找到一种操作简单、安全、试剂易得的氢化方法,即以Pd -C 为催化剂,环己烯为氢供体,甲苯为溶剂,回流反应48h,可以高收率(86%)得

到二氢诺卜醇。其成路线如下。

二氢诺卜醇的制备

向250mL 茄形瓶中加入1710mL(011mol)诺卜醇,10m L(011mol)环己烯,40m L 甲苯,011g 5%Pd -C,升温至回流反应48h,冷至室温,过滤,滤液减压蒸除溶剂,硅胶层析柱分离(V (石油醚)B V (二氯甲烷)=3B 1为洗脱剂),蒸去洗脱剂

得浅黄色油状物1415g,收率86%。1HNMR (CDCl 3),D :3164(m,2H );2132(m,1H );1191~0182(m,10H);1117(s,3H );1101(s,3H)。ESI -MS,m /z :16711[M -H ]-。

Catalytic transfer hydrogenation of nopol Z HANG Lei,X U E Zhon g -hui,C HEN Guo -lian g *(School of Pharmaceutical Eng-i neer i ng,Shenyang Pharmaceutical University ,Shenyang 110016,China),Huaxue Shiji,2007,29(10),640

(接上页)

物质的量比为1B 113时产率达到最大值;继续增加物质的量比,产率便迅速下降,可能是过量的甲胺会跟邻苯二甲酸酐生成N ,N c -二甲基邻苯二甲酰胺。参考文献:

[1]郑凯,姚成.N -甲基-邻苯二甲酰亚胺(NMP)的合成新工艺研究[C].第七届全国精细化学品化学学术会议论文集,2004:137-140.

[2]匡永清,孙晓莉,何炜,等.6-[N -(4-氨基丁基)-N -乙基]氨基-2,3-二氢-1,4-酞嗪二酮的合成[J].第四军医大学学报,2002,23(11):1037-1039.

[3]郑凯,姚成.4-硝基-N -甲基-邻苯二甲酰亚胺合成新工艺[J].石油化工,2004,32(2):145-148.

[4]郑凯,姚成.4-硝基-N -甲基-邻苯二甲酰亚胺的合成新工艺研究[J].江苏化工,2003,31(6):39-41.

[5]诸亚明,瞿渊义.N -甲基邻苯二甲酰亚胺的制备工艺:

中国,1733726[P].2006-02-15.

[6]樊兴君,尤进茂,谭干祖,等.微波促进有机化学反应研究进展[J].化学进展,1998,10(3):285-295.

Synthesis of N -methylphthalim ide under m icrowave irradia -tion BIAN Yong -j un,Z H OU Zhong -qiang *(College of Chemis try and Materials Science,South -Central University for Nationali ties,Wuhan 430074,China),Huaxue Shiji,2007,29(10),639;640Abstract:N -Methylphthali mide was directly synthesized from ph -thalic anhydride and aqueous methylamine under microwave irra -diation.The effects of microwave irradiation power,microwave ir -radiation time,and reactan ts ratio on the yield of N -methylph tha-l imide were studied.The resul ts showed that the most suitable conditions for the reaction were as follows:the microwave irradia -tion power was 119W,the radiation time was 4min,the mass ra -tio between phthalic anhydride and ethanolamine was 1B 13,and the product yield could reach up to 8710%.

Key words:microwave irradiation;synthesis;N -methylphtha-l i mide

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化 学 试 剂2007年10月