2-(3′-苯甲酰基苯基)丙酸的合成研究

Synthesis of 2-(3′-Benzoylphenyl) propoinic Acid

以苯甲酸为原料 ,铁粉做催化剂 ,在 1 4 0～ 1 50℃下滴加Br2 ,然后在 1 50℃下回流反应 1h ,再在 1 60℃回流反应 6h ,反应混合物用碳酸钠的水溶液碱化后 ,再用c(HCl) =2mol/L的盐酸酸化 ,得苯甲酸溴代的产物 ,将溴代物在常压下升华 1 6h ,除去 2 溴苯甲酸 ,收集不升华的 3 溴苯甲酸 (Ⅰ )。将Ⅰ与氯化亚砜在 50～ 60℃反应 ,然后减压蒸馏 ,收集 1 32℃ / 2 4kPa的馏分 ,为 3 溴苯甲酰氯 ,它被滴加到苯与升华过的无水三氯化铝组成的混合液中 ,在 55～ 56℃下回流 ,经Friedel Crafts反应制成苯基 3 溴苯基甲酮 (Ⅱ )。将Ⅱ在对 甲苯磺酸存在下 ,与乙二醇在 78～ 80℃下反应 2 4h ,进行羰基保护 ,制得 2 苯基 2 (3′ 溴苯基 ) 1 ,3 二氧杂环戊烷 (Ⅲ ) ,然后将Ⅲ制成格氏试剂 ,与α 溴化丙酸乙脂在 50～ 60℃下反应 1 5h ,并进一步用盐酸和醋酸混合物与酯类产物一起加热回流 8h ,使酯类水解 ,得产物 2 (3′ 苯甲酰基 苯基 )

Bromobenzoic acid(Ⅰ) was prepared by dropping bromine into benzoic acid at 140-150 ℃ with iron powder as catalyst,and refluxing at 150 ℃ for 1h and then at 160 ℃ for 6 h.The reaction mixture was basified with sodium carbonate and then acidulated with c (HCl)=2 mol/L hydrochloric acid,getting solid product,bromobenzoic acid,which was sublimated under atmospheric pressure for 16 h.The by product 2 bromobenzoic acid was separated and 3 bromobenzoic acid(Ⅰ) was collected.3 Bromobenzoyl chloride was prepared by reaction of Ⅰ with SOCl 2 at 50-60 ℃.Then phenyl 3 bromobenzoyl methanone(Ⅱ) was prepared by Friedel Crafts reaction of benzene and 3 bromobenzoyl chloride.The carbonyl group of Ⅱ was protected by reacting with ethylene glycol at 78-80 ℃ for 24 h,getting 2 phenyl 2 (3′ bromophenyl) 1,3 dioxacyclopentane(Ⅲ) .The title product,2 (3′ benzoylphenyl)propionic acid,was synthesized by coupling reaction of ethyl 2 bromopropionate with Grignard reagent of Ⅲ followed by hydrolytic reaction with a mixture of hydrochloric acid and acetic acid.