5-氨基-1-苄基-4-氰基吡唑的合成及其晶体结构

Synthesis and Crystal Structure of 5-Amino-1-benzyl-4-cyano-pyrazole

由于低的区域选择性,3-氨基-4-氰基吡唑进行烷基化反应均不能产生单一产物。该文采用烷基化合成路线,以3-氨基-4-氰基吡唑为原料,考察了反应溶剂和碱性的缚酸剂对苄基化产物的选择性、收率的影响,在以DMSO、DMF和CH3CN为溶剂时,反应总转化率相差并不明显,但从区域选择性来看,DMSO中反应选择性最好,采用体积分数95%的乙醇重结晶即可得到5-氨基-1-苄基-4-氰基吡唑。通过工艺优化,以DMSO为溶剂,碳酸铯为反应缚酸剂,在100℃下反应,得到了纯度超过98%的产品,重结晶后收率达到62%,产物通过1HNMR和X射线衍射进行了结构表征。单晶X衍射表明,5-氨基-1-苄基-4-氰基吡唑的晶体为单斜晶系,P2(1)c空间群,a=1.433 3(3)nm,b=0.618 7(14)nm,c=2.238 9(5)nm,α=90°,β=93.773(4)°,γ=90°,V=1.981 1(8)nm3,Z=8,Dc=1.329 g·cm-3,λ=0.710 73 nm,μ(Mo Kα)=0.085 mm-1,F(000)=832。

Due to the low regioselectivity,the alkylation of 5-amino-4-cyano-pyrazole always brings forth the mixture of two substitution products. Based on the alkylation method,we start from the raw material of3-amino-1H-pyrazole-4-carbonitrile,and compare the effect of solvents and deacid reagents on the regioselectivity and yield. Although the overall conversion yield does not change so much among DMSO,DMF and CH3 CN,the solvent of DMSO can distinctly improve the regioselectivity. The pure product of 5-amino-1-benzyl-4-cyano-pyrazole can be conveniently recrystallized from 95% ethanol with a separation yield of 62% when using DMSO and Cs CO3 as reaction solvent and deacid reagent,respectively. Its chemical structure is characterized by means of1 H NMR and single crystal X Ray diffraction,which indicates that the product belongs to monoclinic space group P2（ 1） c with a = 1. 433 3（ 3） nm,b =0. 618 7（ 14） nm,c = 2. 238 9（ 5） nm,α = 90°,β = 93. 773（ 4） °,γ = 90°,V = 1. 981 1（ 8） nm^3,Z =8,Dc= 1. 329 g·cm^- 3,λ =0. 710 73 nm,μ（ Mo Kα） =0. 085 mm^- 1,F（ 000） =832.