5-(N,N-二苄基氨基乙酰)水杨酰胺的合成工艺改进  

Process Improvement of 5-(N,N-Dibenzylglycyl)Salicylamide Synthesis

作　　者：刘涛[1] 王亚纳[2] 葛新 LIU Tao WANG Ya-na GE Xin(School of Chemistry and Chemical Engineering, Anqing Normal University, Anqing 246011, China School of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China School of Chemical and Material Engineering, Jiangnan University, Wuxi 214122, China)

机构地区：[1]安庆师范学院化学化工学院,安徽安庆246011 [2]浙江大学化学工程与生物工程学院,浙江杭州310027 [3]江南大学化学与材料工程学院,江苏无锡214122

出　　处：《高校化学工程学报》2016年第5期1153-1157,共5页Journal of Chemical Engineering of Chinese Universities

基　　金：安徽省高校自然科学研究项目(KJ2015A243)

摘　　要：改进了拉贝洛尔的重要中间体5-(N,N-二苄基氨基乙酰)水杨酰胺的合成工艺。首先以廉价易得的水杨酸甲酯为原料,在甲醇中氨解得到水杨酰胺。随后在催化和溶解双重功能的Na Cl-AlCl_3熔盐体系中,140℃下利用乙酰氯酰基化0.5h,得到5-乙酰水杨酰胺。再在Br_2/H_2O_2氧化溴化体系中溴化得到5-溴乙酰水杨酰胺;最后与二苄基氨进行亲核取代反应,制得拉贝洛尔的重要中间体。利用氨解、酰基化、溴化和亲核取代等四步反应,优化工艺参数,降低原料成本和环境污染,总收率达到43.6%。An improved process was developed for the synthesis of 5-（N,N-dibenzylglycyl）salicylamide,which is a key intermediate for labetalol preparation. Methyl salicylate was used as a raw material, andsalicylamide was prepared via ammonolysis in methanol. 5-acetyl salicylamide was obtained by Friedel-Craftsacylation in a nontoxic molten salt system NaC1-AIC13 at 140℃ for 0.5 h. The NaC1-A1C13 molten salt systemwas used as a catalyst and also played a role as a solvent. 5-bromoacetyl salicylamide was obtained afterbromination in an oxidizing bromide system Br2/H202, and 5-（N,N-dibenzylglycyl）salicylamide was preparedfrom nucleophilic substitution reaction of 5-bromoacetyl salicylamide with dibenzylamine. The synthesis routehas four steps including ammonolysis, acylation, a-bromination and nucleophilic substitution reactions with atotal yield of 43.6%, which shows reduced costs and environmental impacts.

关 键 词：拉洛贝尔 溴化 NaCl-AlCl3熔盐体系 5-(N N-二苄基氨基乙酰)水杨酰胺 

分 类 号：TQ236[化学工程—有机化工]