“一锅法”合成(2R,3R)-环氧丁酸的工艺研究

Study on the One-pot Synthesis of(2R,3R)-Epoxybutyric Acid

探索了以L-苏氨酸为原料,"一锅法"合成(2R,3R)-环氧丁酸的工艺。应用Plackett-Burman实验设计筛选影响反应收率的重要因素。考察了浓盐酸、亚硝酸钠、氢氧化钠用量,反应温度,滴加时间以及反应时间对产物产率的影响。研究表明:滴加时间与反应时间对反应的收率影响较大。进一步采用响应面分析法对反应条件进行了优化,得到"一锅法"合成(2R,3R)-环氧丁酸的最佳工艺条件。研究结果表明:最适宜的工艺条件为L-苏氨酸:盐酸:亚硝酸钠:氢氧化钠的摩尔比为1∶1.5∶2∶3,-10℃条件下反应,第一阶段最佳滴加时间为8.3h,第二阶段滴加时间为8.3h,反应时间为3.5h,(2R,3R)-环氧丁酸的收率为93.5%。

（2R,3R）-epoxybutyric acid were prepared by ＂one-pot＂ process by using L-threonine as starting materials.Firstly,the Plackett-Burman design was used to evaluate the effects of eight variables including amount of hydrochloric acid,sodium nitrite,sodium hydroxide,reaction temperature,dropwise adding time and reaction time.By analyzing the statistical regression,dropwise adding time and reaction time were found to be the most important factors.Secondly,the experimental design of steepest ascent was used to approach the best reaction condition.On this basis,Box-Benhnken Design was used to optimize the reaction condition.Then the optimal conditions was obtained as followed： the molar ratio of L-threonine：hydrochloric acid：sodium nitrite：sodium hydroxide was 1： 1.5： 2：3,the reaction was carried out under-10℃,dropwise added in 8.3 hours at first step,8.3 hours at second step and the reaction time was 3.5 hours with the yield of 93.5%.