2-氯-3-氰甲基吡啶的合成及表征

对2-氯-3-氰甲基吡啶(Ⅳ)的合成进行了研究。首先,起始原料2-氯烟酸和SOCl2在甲苯中回流酰化,再加入甲醇酯化,得到2-氯烟酸甲酯(Ⅰ),产率94%。Ⅰ在NaBH4-MeOH/THF还原体系中,于70℃反应生成2-氯-3-羟甲基吡啶(Ⅱ),产率93%。Ⅱ和SOCl2在二氯甲烷中,0℃反应生成2-氯-3-氯甲基吡啶(Ⅲ),产率92%。最后,Ⅲ和NaCN在DMSO和水体系中,100℃时发生氰基取代,生成2-氯-3-氰甲基吡啶(Ⅳ),产率86%。该合成路线的总收率达70%。中间产物和目标化合物经元素分析,FTIR和1HNMR进行了表征。

Synthesis and Characterization of 2-Chloro-3-cyanomethylpyridine

A synthetic route of 2-chloro-3-cynaomethylpyridine(Ⅳ) was investigated.First of all,2-chloro nicotinic acid as the initial reactant was chlorinated via SOCl2 in toluene under reflux and then esterified by using methanol to give methyl 2-chloro nicotinate(Ⅰ) in 94% yield.Methyl 2-chloro nicotinate(Ⅰ) was reduced by NaBH4-MeOH in THF at 70 ℃ to produce 2-chloro-3-hydroxylmethyl pyridine(Ⅱ) in 93% yield.2-Chloro-3-hydroxylmethyl pyridine(Ⅱ) then reacted with SOCl2 in dichloromethane at 0 ℃ to give 2-chloro-3-chloromethylpyridine(Ⅲ) in 92% yield.Finally,2-chloro-3-chloromethylpyridine(Ⅲ) was nitrile substituted by using NaCN in DMSO/water system at 100 ℃ to obtain the final product,2-chloro-3-cynaomethylpyridine(Ⅳ),in 86% yield.The overall yield is up to 70%.The intermediates and the target compound were characterized by elementary analysis,FTIR and 1HNMR,respectively.