氨基吡唑衍生物的合成

Synthesis of amino pyrazole derivatives

目的 优化氨基吡唑类衍生物的合成工艺.方法 以丙二氰为起始原料,首先在碱性条件下聚合为二聚物,然后与85％的水合肼关环得3-氨基-4-氰基-5-氰甲基-2-吡唑,最终在不同的酸碱条件下水解,得到不同的氨基吡唑甲酸类衍生物.结果 考察了3步反应工艺对产品收率的影响,结果表明,较佳的反应条件为：聚合反应中,室温条件下,以氢氧化钠为碱试剂、乙醇为溶剂,二聚物的收率为86.1％;关吡唑环反应中,n（二聚物）：n（肼）=1∶3.5,产物收率为86.2％;碱性条件下水解反应,95 ～ 100℃条件下,10 mol/L氢氧化钠溶液中反应10 h,5-氨基-1-吡唑-3-乙酸收率为79.8％;酸性条件下水解反应,85℃条件下,浓硫酸∶乙酸（体积比）=1∶1,反应24 h,3-氨基-4-氰基吡唑-5-甲酸收率为69.7％.结论 本工艺路线环境友好,原料易得,便于操作.同时,所得产物经1HNMR及MS确证.

Objective To optimize the synthetic process of amino pyrazole derivatives. Methods Malononitrile was first adopted as raw material to polymerize into a dimer under alkaline conditions, which then reacted with 85% hydrazine hydrate, producing 3 - amino - 4 - cyano - 5 - cyanomethyl - 2 - pyrazole. The resultant product was hydrolyzed using different pH reagents to give 2 - （ 3 - amino - 1H - pyrazol - 5 - yl） acetic acid and 2 - （ 3 - amino - 4 - cyano - 1 H- pyrazol- 5 -yl） acetic acid respectively. Results We investigated the effects of the three -step reaction process on product yield. The results indicate the following preferable reaction conditions： sodium hydroxide and ethanol serve as alkaline reagent and solvent respectively for polymerization at room temperature, with a yield of 86.1% ; the molar ratio of dimers and hydrazine is 1：3.5 during pyrazole ring closure, with a yield of 86.2% ; alkaline hydrolysis requires reaction in 10 mol/L of sodium hydroxide solution at 95 - 100 ℃ for 10 hours, giving a yield of 79.8% ; acidic hydrolysis requires concentrated sulfuric acid and acetic acid in 1 ： 1 （V/V） ratio at 85 ℃ for 24 hours, giving a yield of 69.7%. Conclusion The process route has easy access to raw material. It is easy to run and environment -friendly. In addition, the compounds were identified by 1HNMR and MS.