3,5-二甲基苯酚合成工艺改进

Improved synthesis of 3,5-dimethylphenol

摘要:

以乙酰乙酸乙酯和乙醛为起始原料，以碳酸钠作为碱，经过Robinson环合反应得到4-乙氧羰基-3,5-二甲基-2-环己烯-1-酮，收率为95 %。对碳酸钠体系催化的Robinson环合反应进行应用拓广，在该体系催化下，脂肪醛和芳香醛底物均可顺利转化为相应二取代环己烯酮产物。环合产物4-乙氧羰基-3,5-二甲基-2-环己烯-1-酮经皂化脱羧过程可定量转化为关键中间体3,5-二甲基-2-环己烯酮，收率为99 %。将3,5-二甲基-2-环己烯酮直接脱氢芳构化，得到了目标产物3,5-二甲基苯酚。采用1HNMR和13CNMR对产物及中间体结构进行了表征。本文建立的工艺条件下，3,5-二甲基苯酚的总收率为66 %。该工艺也应用于3-甲基-5-丙基苯酚的合成，具有一定的普适性。

Abstract:

4-Ethoxycarbonyl-3,5-dimethyl-2-cyclohexen-1-one was obtained in 95 % yield via Robinson annulation of ethyl acetoacetate with acetaldehyde over sodium carbonate. The Robinson annulation catalyzed by sodium carbonate system was extended to diverse substrates. Under the catalysis of this system, both aliphatic aldehydes and aromatic aldehydes can be smoothly converted into corresponding disubstituted cyclohexenones. The cyclization product, 4-ethoxycarbonyl-3,5-dimethyl-2-cyclohexen-1-one can be almost quantitatively converted into the key intermediate 3,5-dimethyl-2-cyclohexenone through saponification and decarboxylation, and the yield of 3,5-dimethyl-2-cyclohexenone was 99 %. Direct dehydrogenation aromatization of 3,5-dimethyl-2-cyclohexenone was successfully realized to yield 3,5-dimethylphenol. The structures of the product and intermediates were characterized by 1HNMR and 13CNMR. The total yield of 3, 5-dimethylphenol was 66 % under the strategy established in this paper. Besides, this method was successfully applied to the synthesis of 3-methyl-5-propylphenol, which exhibited universal applicability.