头孢他定中间体α-溴代异丁酸叔丁酯的合成

The synthetic study of a ceftazidine intermediate, tert-butyl α-bromoisobutyrate

目的 探讨合成α-溴代异丁酸叔丁酯的最佳工艺条件。方法 以异丁酸、氯化亚砜、叔丁醇和单质溴为原料,通过酰化、酯化、溴代三步反应合成α- 溴代异丁酸叔丁酯。结果 酰化,异丁酸与氯化亚砜的摩尔比1∶1 . 3,不加溶剂,反应时间1 . 5h ,收率86 . 8%;酯化,碳酸钾为催化剂,异丁酰氯与叔丁醇的摩尔比1∶1. 3,异丁酰氯与溶剂苯的摩尔比1∶2 5 0 ,反应时间3h ,收率6 3 . 2 %;溴代,溴与异丁酸叔丁酯的摩尔比1∶1 2 ,反应时间2 . 5h ,收率81 . 2 %。结论 本法简便、稳定、污染小、产品纯度和收率高,对工业化放大应作进一步探讨。

Objective: To study the optimum synthetic method of tert-butylα-bromoisobutyrate. Methods: Tert-butyl α-bromoisobutyrate was prepared from iso-butanoic acid, thionyl chloride, tert-butanol and bromine through acylation, esterification and bromization. Results: The optimum conditions of acylation as follows: the ratio of iso-butanoic acid to thionyl chloride was 1∶1.3 (mol∶mol), time was 1.5 h without solvention. Under this conditions, the yield of iso-butanoyl chloride is 86.8%. The optimum conditions of esterification as follows: the ratio of iso-butanoyl chloride to tert-buta-nol was 1∶1.3 (mol∶mol), the ratio of iso-butanoyl chloride to benzene was 1∶250 (mol∶mol), time was 3 h with potassium carbonate as the catalyst. Under this conditions, the yield of tert-butyl isobutyrate is 63.2%. The optimum conditions of bromization as follows: the ratio of bromine to iso-butyrate was 1∶1.2, time was 2.5 h. Under this conditions, the yield of tert-butyl α-bromoisobutyrate is 81.2%. Conclusion: The method is simple and reliable, and has little pollution, high purity and yield. The wide industrial application needs to be further probed into.