N-(2-甲基丙基)-N-([2-(4-甲硫基-苯氧甲基)-噻唑-4-基]-甲基)-2-呋喃甲酰胺的合成及抗菌活性初筛

Synthesis of N-isobutyl-N-({2-\[(4-methylthio-phenoxy)methyl\]thiazol-4-yl}methyl)furan-2-carboxamide and Evaluation of Their Antibacterial Activity in Vitro

以对甲硫基苯酚和氯乙腈为原料,碳酸钠催化下经烷基化得2-(4-甲硫基苯氧基)-乙腈(3);再与五氧化二磷反应制备得2-(4-甲硫基苯氧基)-硫代乙酰胺(4);经与1,3-二氯丙酮缩合得到噻唑(5);然后与异丁胺反应得2-甲基-N-[(2-(4-甲硫基-苯氧甲基)-4-噻唑)-甲基]-丙胺(6);最后与呋喃甲酰氯反应制备得到目标化合物N-(2-甲基丙基)-N-([2-(4-甲硫基-苯氧甲基)-4-噻唑]-甲基)-2-呋喃甲酰胺(1),经上述5步反应,总收率为19.3%.对目标化合物(1)做抗菌活性初筛,发现其对细菌F.moniliform和G.gramini表现出较高的抑制活性.

2-(4-methylthio-phenoxy)acetonitrile(3)was synthesized with 4-methylthio-phenol and 2-chloroacetonitrile catalyzed by Na_(2)CO_(3),which was reacted with P_(2)O_(5) to afford 2-(4-methylthio-phenoxy)ethanethioamide(4).Then,4-(chloromethyl)-2-\[(4-methylthio-phenoxy)methyl\]thiazole(5)was prepared via a condensation with compound(4)and 1,3-dichloropropan-2-one.2-Methyl-N-({2-\[(4-methylthio-phenoxy)methyl\]thiazol-4-yl}methyl)propan-1-amine(6)was synthesized with compound(5)and 2-methylpropan-1-amine.The title compound N-isobutyl-N-({2-\[(4-methylthio-phenoxy)methyl\]thiazol-4-yl}methyl)furan-2-carboxamide(1)was obtained via Friedel-Crafts acylation between compound(5)and furan-2-carbonyl chloride.The overall yield is 19.3%after the above five-step reaction.The compound(1)shows the antibacterial activity against F.moniliform and G.gramini.The results provide some reference for the research of antibacterial activity of these compounds.