摘要
为了解决(S)-N,N-二甲基-3-羟基(2-噻吩基)丙胺合成工艺中操作较复杂,产率低的问题,以2-乙酰噻吩、二甲胺盐酸盐、多聚甲醛为起始原料,经曼尼希反应、硼氢化钠还原和S-(+)-扁桃酸拆分合成(S)-N,N-二甲基-3-羟基(2-噻吩基)丙胺.采用单因素分析方法考察了浓盐酸的用量、投料比、反应时间对产物收率的影响,得到各步反应的最佳工艺条件:曼尼希反应的最佳投料比为n(2-乙酰噻吩)∶n(浓盐酸的用量)=15∶1,产物收率可达90.6%;还原反应在25℃下,投料比为n(3-二甲胺基-1-(2-噻吩基)-1-丙酮盐酸盐)∶n(硼氢化钠)=1∶0.55,反应6h时效果最佳;拆分反应的最佳条件是反应温度85℃,反应45min.优化后反应的总收率可达60.3%,目标产物经核磁共振氢谱、质谱确认.该合成工艺原料便宜易得,反应条件温和,工艺操作简便适合工业化生产.
To solve the problems of complicated production process conditions,low production rate of （S）-N,N-Dimethyl-3-（2-thienyl）-3-hydroxypropanamine,2-acetyl thiophene,dimethylamine hydrochloride and paraformaldehyde were applied as raw materials to prepare （S）-N,N-Dimethyl-3-（2-thienyl）-3-hydroxypropanamine through Mannich,reduction and resolution reaction.The influence of concentrated hydrochloric acid dosage,feed ratio,reaction time on the product yield was studied by single factor analysis method.The yield is 90.6％ when the molar ratio of （2-acetyl thiophene） ∶（concentrated hydrochloric） is 15 ∶ 1 in the Mannich reaction.The optimum conditions of the reduction reaction are demonstrated at 25 ℃ for 6h with molar ratio of （3-Dimethylamino-1-（2-thienyl）-1-propanone hydrochloride） ∶ （Sodium borohydride）=1 ∶ 0.55.The best condition of resolution reaction is at 85 ℃ for 45 min.The total yield is 60.3％ after optimum reaction and the target compound was elucidated by nuclear magnetic resonance spectrum spectroscopy and mass spectrum.This method is feasible for industry with low cost,mild condition,easy operation.
出处
《武汉工程大学学报》
CAS
2013年第12期22-26,共5页
Journal of Wuhan Institute of Technology
