5-羟基苯并呋喃-6-甲酸的合成研究

Synthesis of 5-Hydroxybenzofuran-6-carboxylic Acid

以2,5-二羟基苯甲酸为原料,经酯化、取代、多聚磷酸催化傅克烷基化、酯水解4步反应制备目标化合物,4步反应总收率52. 5%。其结构及中间体经1HNMR、13CNMR和ESI-MS确证。并分别对每一步影响产物收率的因素进行了研究。确定酯化条件:无水乙醇为溶剂,n(SOCl2)∶n(2,5-二羟基苯甲酸)=1. 5∶1,回流条件下反应3 h,收率为93%。取代反应条件:K2CO3为碱,n(2-溴-1,1-二甲氧基乙烷)∶n(2,5-二羟基苯甲酸乙酯)=1. 3∶1,反应在丙酮溶剂中回流12 h,5-(2,2-二甲氧基乙氧基)-2-羟基苯甲酸乙酯最高收率为78%。傅克烷基化反应条件:甲苯为溶剂,n(PPA)∶n(5-(2,2-二甲氧基乙氧基)-2-羟基苯甲酸乙酯)=0. 5∶1,反应在80℃下进行2 h,收率为77%。水解条件:甲醇/水混合溶剂,n(Na OH)∶n(5-羟基苯丙呋喃-6-甲酸乙酯)=3∶1,50℃时反应4 h,收率为94%。

The target compound was synthesized from 2,5-dihydroxybenzoic acid via four steps in a total yield of 52. 5% by esterification reaction,substitution reaction,Friedel-Crafts alkylation in the presence of polyphosphoric acid and hydrolysis of ester.The structures of intermediates and the product were confirmed by1 HNMR,13 CNMR and ESI-MS.The effect of the reaction conditions on the yields of each step was investigated respectively.The optimal esterification reaction conditions were absolute ethanol as solvent,n( SOCl2) ∶n( 2,5-dihydroxybenzoic acid) = 1. 5 ∶1,reflux for 3 h,the yield was 93%.The optimal substitution reaction were K2 CO3 as base,n( 2-bromo-1,1-two methoxy ethane) ∶ n( ethyl 2,5-dihydroxybenzoate) = 1. 3 ∶ 1,5-( 2,2-dimethoxyethoxy)-2-hydroxybenzoate was obtained in 78% yield with the reaction reflux for 12 h in acetone.The optimal Friedel-Crafts alkylation reaction conditions were toluene as solvent,n( PPA) ∶n( 5-( 2,2-dimethoxyethoxy)-2-hydroxybenzoate) = 0. 5 ∶1,at 80 ℃ for 2 h,the yield was 77%.The optimal hydrolysis of ester reaction conditions were methanol/water as solvent,n( Na OH) ∶n( 5-hydroxyphenylfurfuryl-6-ethyl formate) = 3 ∶1,at 50 ℃ for 4 h,the yield was 94%.