4-氯-1,7-二羟基二氢化茚的合成及意外醚化反应的研究

Study on the Synthesis and Unexpected Etherification of 4-Chloro-indan-1,7-diol

以对氯苯酚 ( 8)为原料、三乙胺作缚酸剂 ,与丙烯酰氯反应生成对氯苯酚丙烯酸酯 ( 7) ,7与AlCl3 共热 15 5℃ ,首先发生Fries重排 ,然后关环得到 4 氯 7 羟基二氢化茚 1 酮 ( 6) ,再用NaBH4/CH3 OH或LiAlH4/THF还原 6的羰基得到 4 氯 1,7 二羟基二氢化茚 ( 5 ) .条件控制不当易产生两个意外的醚化产物 4 氯 1 甲氧基 7 羟基二氢化茚 ( 9)和自身醚化产物 10 ,9的结构经X射线单晶衍射分析确证 ,并提出生成 10的可能机理为 5的醇羟基极易通过分子内催化形成碳正离子、进而与另一分子 5形成自身醚化产物 10 .因此 ,还原反应完成后的后处理应避免长时间放置和加热 ,以减少醚化产物的生成 .化合物 5 ,9。

4-Chlorophenol (8) reacted with acryloyl chloride in. the presence of Et3N as acid scavenger to give acrylic acid 4-chlorophenyl ester (7). Compound 7 was heated at 155 degreesC with AlCl3 to undergo Fries rearrangement and ring closure affording 4-chloro-7-hydroxy-indan-1-one (6). Reduction of the carbonyl group of 6 with NaBH4/CH3OH or LAlH4/THF gave 4-chloro-indan-1,7-diol (5). Two unexpected ethers (methyl etherified product 9 and dimerized ether 10) were formed in this reduction if the workup procedure is not controlled carefully. The structure of 9 was determined by X-ray diffraction analysis and the mechanism of etherification was proposed. 1-Hydroxy group of 5 is easy to form its ether derivative 10 through an intramolecular catalysis of carbon cation formation, followed by the reaction with compound 5 itself. Therefore, the workup of the reaction mixture and separation of product 5 should be done as soon as possible after the reduction was completed in order to prevent the formation of ether byproducts. New compounds 5, 9 and 10 were characterized by H-1 NMR, C-13 NMR, MS and elemental analysis or HRMS.