N-二氯乙酰基-5-氯-2,3-二氢苯并噁唑的合成

Synthesis of N-Dichloroacetyl-5-chloro-2,3-dihydro-benzoxazole

探索了以廉价的对2-氨基-4-氯苯酚、二氯甲烷和二氯乙酰氯为原料,经环合及酰基化反应获得N-二氯乙酰基-5-氯-2,3-二氢苯并噁唑的全合成路线。利用正交实验设计分别研究了反应过程中溶剂效应、反应温度、搅拌时间、缚酸剂对中间体5-氯-2,3-二氢苯并噁唑产率的影响及反应溶剂、温度、搅拌时间及原料的摩尔比对终产物产率的影响。确定了环合反应合成中间体5-氯-2,3-二氢苯并噁唑的优化实验条件为:以N,N-二甲基乙酰胺为溶剂,反应温度为90℃,搅拌时间1 h,缚酸剂为氢氧化钠时产率达到72.6%;酰基化反应合成标题化合物的优化实验条件为:N,N-二甲基乙酰胺做溶剂,反应温度为20～25℃,搅拌时间2 h,5-氯-2,3-二氢苯并噁唑与二氯乙酰氯的摩尔比为1:1.2时产率达到91.8%。产物结构经红外光谱、核磁共振和元素分析进行表征。本方法原料廉价易得、路线简单、反应条件温和、操作简便,适于工业化生产。

The total synthetic route of using the ring closure and acylation reactions,to synthesize the N-dichloroacetyl-5-chloro-2,3-dihydro-benzoxazole with 2-amino-4-chlorophenol,dichloromethane and dichloroacetyl chloride as raw materials was investigated.The factors affecting the yields of the intermediate 5-chloro-2,3-dihydro-benzoxazole and the title compound N-dichloroacetyl-5-chloro-2,3-dihydro-benzoxazole,such as the polarity of solvent and the species of attaching acid agent used,reaction temperature,stirring time,and the molar ratio of reactants,were studied by orthogonal experiments,and the results were discussed.The optimum experimental conditions for the preparation of the intermediate 5-chloro-2,3-dihydro-benzoxazole were found as following： N,N-dimethylacetamide is used as solvent,reaction temperature used is 90℃,stirring time is 1 h and NaOH is used as attaching acid agent.Under above conditions,the yield of 5-chloro-2,3-dihydro-benzoxazole is 72.6%.The optimum synthetic conditions found for preparing the title compound are as follows： N,N-dimethylacetamide is used as solvent,reaction temperature used is 20～25℃,stirring time is 2 h and the molar ratio of 5-chloro-2,3-dihydro-benzoxazole and dichloroacetyl chloride is 1：1.2;and the yield of the title compound could be 91.8%.The structures of the obtained compounds were characterized by IR,1H-NMR,13C-NMR and ultimate analysis.The proposed synthetic route is simple,the reaction conditions are mild and the raw materials are cheap and easy to be obtained.