N,N-二甲基-10H-2-吩噻嗪磺酰胺合成工艺的研究

Research on synthesis of N,N-dimethyl-10H-phenothiazine-2-sulfonamide

摘要:

N,N-二甲基-10H-2-吩噻嗪磺酰胺是治疗精神分裂药物哌泊噻嗪的一个关键中间体。本文以邻溴苯胺为起始原料，经缩合、水解、N,N-二甲基-3-硝基-4-氯苯磺酰胺缩合、锌粉还原、铜催化Ullmann反应，得到目标化合物。并考察了缩合反应不同溶剂、碱、反应温度，还原反应还原剂的用量，Ullmann反应催化剂的用量、反应时间、反应温度对反应收率的影响。优化后5步反应总收率可达45.5%，且反应条件温和，后处理简便，产品经ESI-MS和1HNMR确证结构。

Abstract:

N,N-dimethyl-10H-phenothiazine-2-sulfonamide is the very important intermediate of Pipothiazine which is the representative drug of anti-psychotic disorders.In this study, o-bromoaniline was condensed and hydrolysesed , then condensed by N,N-dimethyl-4-chloro-3-nitrobenzenesulfonamide,and reduced by zinc dust,after via Ullmann reaction to give the final target compounds. The effects of different solvent/base、temperature on the yield of condensation,reducing agent proportion on the yield of the reduction,and catalyst agent proportion、reaction temperature and reaction time on the yield of the Ullmann reaction were studied.After 5 steps,the total yield could reach up to 45.5%, the reaction condition was mild,and easily to be treated,the structure of the targer compound was confirmed by means of ESI-MS and 1HNMR.