N-亚硝基新烟碱类化合物的合成

以3-氨甲基吡啶和二苯甲酮为主要原料,对甲苯磺酸作催化剂,甲苯作溶剂,合成N-二苯亚甲基-3-氨甲基吡啶(1),以化合物(1)为原料合成新烟碱。以新烟碱为先导化合物,设计合成了假木贼碱和N-亚硝基新烟碱,再以假木贼碱合成N-亚硝基假木贼碱。考察了催化剂、反应时间和原料比例对化合物(1)产率的影响;二异丙基氨基锂(LDA)用量对新烟碱产率的影响;反应温度和时间对亚硝基新烟碱产率的影响。采用1 H NMR和MS等对所合成的化合物结构进行了证实。实验结果表明:当n(3-氨甲基吡啶)∶n(二苯甲酮)=1∶1.25,选用对甲苯磺酸作催化剂,回流反应3h时,化合物(1)收率高达86.4%;n(3-氨甲基吡啶和二苯甲酮)∶n(LDA)=1∶1.1时,新烟碱的收率为85.5%;当反应温度为0℃,反应时间为6.0h时,N-亚硝基新烟碱的收率为81.0%。

SYNTHESIS OF N-NITROSOANATABINE COMPOUNDS

N-(diphenylmethylene)(pyridin-3-yl) methanamine(compound 1) was synthesized first with 3-aminomethyl pyridine and benzophenone as main raw materials,toluene as addition agent,p-toluenesulfonic acid as catalyst,and then compound(1) was used as material to synthesize Anatabine.Finally,Anabasine and N-Nitrosoanatabine were synthesized from Anatabine,and N-Nitrosoanabasine was synthesized from Anabasine.The effects of catalyst,reaction time and raw material ratio on the yield of the compound(1),LDA dosage on Anatabine yield,the reaction temperature and time on N-Nitrosoanatabine were researched.Structures of the new compounds have been characterized by 1H NMR and MS.The optimum conditions were found as follows: yield of compound(1) could be up to 86.4% when n(3-aminomethylpyridine)∶n(benzophenone) =1∶1.25,p-toluenesulfonic acid was used as catalyst and reflux reaction was 3 h,yield of Anatabine could be 85.5% when n(N-(diphenylmethylene)(pyridin-3-yl) methanamine)∶n(LDA)=1∶1.1,yield of N-Nitrosoanatabine could be 81.0% when the reaction temperature was 0 ℃ and reaction time was 6 h.