5-（N,N-二苄基氨基乙酰）水杨酰胺的合成工艺改进

摘要

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, and salicylamide was prepared via ammonolysis in methanol. 5-acetyl salicylamide was obtained by Friedel-Crafts acylation in a nontoxic molten salt system NaCl-AlCl3 at 140℃ for 0.5 h. The NaCl-AlCl3 molten salt system was used as a catalyst and also played a role as a solvent. 5-bromoacetyl salicylamide was obtained after bromination in an oxidizing bromide system Br2/H2O2, and 5-(N,N-dibenzylglycyl)salicylamide was prepared from nucleophilic substitution reaction of 5-bromoacetyl salicylamide with dibenzylamine. The synthesis route has four steps including ammonolysis, acylation, α-bromination and nucleophilic substitution reactions with a total yield of 43.6%, which shows reduced costs and environmental impacts.%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NaCl-AlCl3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Br2/H2O2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%。