1-(3-甲基-1-苯基-1H-吡唑-5-基)哌嗪合成方法改进  

Improved Synthesis of 1-(3-methyl-1-phenyl-1H-pyrazole-5-yl)Piperazine

作　　者：顾娜 杨永建 魏佳佳 穆丽娜 周安琪 宋航 柯浩 李树安 张珍明 GU Na;YANG Yongjian;WEI Jiajia;MU Lina;ZHOU Anqi;SONG Hang;KE Hao;LI Shu’an;ZHANG Zhenming(School of Environmental and Chemical Engineering,Jiangsu Ocean University,Lianyungang 222005,China;School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China)

机构地区：[1]江苏海洋大学环境与化学工程学院,江苏连云港222005 [2]江苏海洋大学药学院,江苏连云港222005

出　　处：《江苏海洋大学学报（自然科学版）》2021年第4期60-66,共7页Journal of Jiangsu Ocean University:Natural Science Edition

基　　金：国家自然科学基金资助项目(21606095);江苏省优势学科建设工程资助项目(5511201901X);连云港市“花果山英才计划”科技副总项目(2019012);江苏海洋大学博士启动基金资助项目(KQ16001);江苏省研究生科研与实践创新计划项目(KYCX19_2269,KYCX19_2270,KYCX19_2292);江苏省苏北科技专项(SZ-LYG202017);江苏省大学生创新创业训练计划项目(SD201911641104003)。

摘　　要：以1-Boc-哌嗪(a)和乙酰乙酸乙酯(b)为起始原料,仅用甲苯作溶剂,按n(a)∶n(b)=1.0∶1.0投料,加热至110℃反应9 h生成N-Boc乙酰乙酰基哌嗪(c),中间体c的甲苯溶液无需经过复杂处理与劳森试剂(LR)在50~55℃条件下反应4 h,碱性条件下再与苯肼在65~70℃反应6 h制得5-(4-叔丁氧羰基哌嗪-1-基)-3-甲基-1-苯基吡唑(d),最后,经盐酸脱保护制得1-(3-甲基-1-苯基-1H-吡唑-5-基)哌嗪,总收率为40.4%,质量分数为97.8%。采用FTIR,LC-MS及^(1)H NMR对产物进行了表征。N-Boc-acetoacetylpiperazine(c)was synthesized by using 1-Boc-piperazine(a)and ethyl acetoacetate(b)as raw materials,with only toluene as solvent under the conditions of n(a):n(b)=1.0∶1.0,reaction time of 9 h and temperature of 110℃.The 5-(4-tert-butoxycarbonylpiperazin-1-yl)-3-methyl-1-phenylpyrazole(d)was synthesized by the reaction of toluene solution of intermediate c with Lawson reagent(LR)at 50—55℃for 4 h without complicated treatment,and then with phenylhydrazine at 65—70℃for 6 h under alkaline conditions.Finally,1-(3-methyl-1-phenyl-1H-pyrazole-5-yl)piperazine was synthesized by de-protection with hydrochloric acid.The overall yield and purity of the product were 40.4%and 97.8%.The structure of the product was characterized by FTIR,LC-MS and ^(1)H NMR.

关 键 词：1-Boc-哌嗪 乙酰乙酸乙酯 N-Boc乙酰乙酰基哌嗪 碱性条件 

分 类 号：TQ530[化学工程—煤化学工程]