4-(氨甲基)-N-甲氧基苯脒合成研究  

Synthesis of 4-(aminomethyl)-N-methoxybenzene-l-carboximidamide

作　　者：仝红娟 徐小娜 王艳娇[1] 唐文强 刘斌[1] TONG Hong-juan;XU Xiao-na;WANG Yan-jiao;TANG Wen-qiang;LIU Bin(Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis,School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,China;School of pharmaceutical&Chemical Engineering,Xianyang Vocational Technical College,Xianyang 712000,China)

机构地区：[1]咸阳市分子影像与药物合成重点实验室,陕西国际商贸学院医药学院,陕西西安712046 [2]咸阳职业技术学院医药化工学院,陕西咸阳712046

出　　处：《化学研究与应用》2024年第8期1950-1955,共6页Chemical Research and Application

基　　金：陕西省自然科学基金项目(面上)(2024JC-YBMS-733)资助;咸阳市分子影像与药物合成重点实验室项目(2021QXNL-PT-0008)资助;2023年咸阳市科技局重点研发计划项目(L2023-ZDYF-SF-030)资助。

摘　　要：本研究报道一种结构新颖的苯脒化合物(1)的合成。以1,4-二溴苯(2)为原料,首先经历氰基取代反应得到4-溴苯腈(3),然后,中间体(3)与甲基硼酸(4)发生Suzuki偶联反应得到4-甲基苯腈(5),中间体(5)再发生NBS溴代反应得到4-(溴甲基)苯腈(6),随后,中间体(6)与双(叔丁氧羰基)胺发生亲核取代反应得到N,N-二(叔丁氧羰基)-4-氰基苯甲胺(7),中间体(7)再与甲氧基胺盐酸盐(8)发生亲核加成反应,得到N,N-二(叔丁氧羰基)-4-(N'-甲氧基脒基)苯甲胺(9),最后,中间体(9)在酸性条件下脱除Boc保护基,得到产物4-(氨甲基)-N-甲氧基苯脒盐酸盐(1)。中间体及产物结构通过~1H NMR和ESI-MS进行表征,其中产物结构进一步通过^(13)C NMR表征。The synthesis of novel benzamidine compound(1) was reported.Firstly,4-bromobenzonitrile(3) was obtained from 1,4-dibromobenzene(2) via cyano-substitution reaction.Then,the intermediate(3) underwent Suzuki coupling reaction with methylboric acid(4) to obtain 4-methylbenzonitrile(5).The intermediate(5) underwent NBS bromination reaction to obtain 4-(Bromomethyl)benzonitrile(6).Intermediates(6) underwent nucleophilic substitution reactions with bis(tert-butyloxy-carbonyl) amines to obtain tert-butyl N-((tert-butoxy) carbonyl)-N-((4-cyanophenyl) methyl) carbamate(7),intermediates(7) underwent nucleophilic addition reactions with methoxyamine hydrochloride(8) to obtain tert-butyl N-((tert-butoxy) carbonyl)-N-((4-((E)-N'-methoxycarbamimidoyl) phenyl) methyl) carbamate(9).Finally,the intermediate(9) removed the Boc protective group under acidic conditions to give the product 4-(aminomethyl)-N-methoxybenzene-l-carboximidamide hydrochloride(1).The intermediate and product structures were characterized by ~1H NMR and ESI-MS,and the product structures were further characterized by ^(13)C NMR.

关 键 词：脒类化合物 氰化反应 SUZUKI偶联反应 溴代反应 亲核取代反应 

分 类 号：O625.6[理学—有机化学]