5-氨基-1-苄基-4-氰基吡唑的合成及晶体结构研究

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

摘要:

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、产率影响，在以DMSO、DMF和CH3CN作为溶剂时，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，可采用简单的95%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%合格的产品，重结晶收率后收率达到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 = 1.4333(3) nm, b = 0.6187(14) nm，c = 2.2389 (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 = 0.71073 nm，μ (Mo Kα) = 0.085 mm-1，F(000) = 832。

Abstract:

Due to the low region-selectivity, the alkylation of 5-amino-4-cyano-pyrazole always bring forth the mixture of two substitution products. Based on the alkylation method, We start from the raw material of 3-amino-1H-pyrazole-4-carbonitrile, and compare the effect of solvents and deacid reagents on the region-selectivity and yield. Although the overall conversion yield doesn’t change so much among DMSO, DMF and CH3CN, the solvent of DMSO can distinctly improve the region-selectivity. 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 CsCO3 as reaction solvent and deacid reagent, respectively. Its chemical structure is characterized with 1H NMR and single crystal X Ray diffraction, which belongs to monoclinic space group P2(1)c with a = 1.4333 (3) nm, b = 0.6187(14) nm, c = 2.2389 (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 = 0.71073 nm, μ (Mo Kα) = 0.085 mm-1, F (000) = 832.