Synthesis of 4-Amino-5-biphenyloxy-3-halo-2(5H)-furanones

Abstract

Two novel 5-biphenyloxy-3,4-dihalo-2(5H)-furanones are synthesized via the direct dehydrative etherification reactions of biphenyl-4-ol with mucochloric acid and mucobromic acid, respectively, using sulfuric acid as a catalyst in toluene at reflux temperature. Taking them as intermediates, the tandem Michael addition-elimination reaction with different representative aliphatic amines is carried out in the presence of KF as a base and catalyst at room temperature. Sixteen 4-amino-5-biphenyloxy-3-halo-2(5H)-furanones are obtained, and the isolated yields are 43%～79% (mostly over 55%). The structures of all newly synthesized compounds were systematically characterized by FTIR, UV, 1 H NMR, 13 C NMR, MS and elemental analysis. This investigation affords an important novel strategy for the synthesis of different 2(5H)-furanone derivatives having potential bioactivity, especially for the synthesis of 2(5H)-furanones simultaneously with biphenyl and amino structure. Keywords 2(5H)-furanone; biphenyl structure; synthesis; aliphatic amine; tandem Michael addition-elimination reaction 2(5H)-呋喃酮结构单元广泛存在于天然产物 [1] 与药 物分子 [2～4] 中, 使 2(5H)-呋喃酮化合物的合成在药物开 发中近来受到广泛关注 [5～8] . 许多联苯类化合物(图 1)具 有抗菌、抗癌等生物活性 [2,9] , 使联苯结构单元在药物分 子的设计与合成中最近也越来越受到重视 [10,11] . 但是, 目前仅有极少的文献报道将 2(5H)-呋喃酮结构与联苯 结构同时构建于潜在生物活性分子中的研究 [2,11] .因此, 在前期 2(5H)-呋喃酮化学研究的基础上 [6,12] ,