3,5-二甲基苯酚合成工艺改进

Improved synthesis of 3,5-dimethylphenol

以乙酰乙酸乙酯和乙醛为起始原料、无水碳酸钠为碱,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%。对无水碳酸钠体系催化的 Robinson 环合反应进行了应用拓展,在该体系催化下,脂肪醛和芳香醛底物均可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;HNMR 和;CNMR 对产物及中间体结构进行了表征。在本文建立的工艺条件下,3,5-二甲基苯酚的总收率为 66%。该工艺适用于 3-甲基-5-丙基苯酚的合成,具有一定的普适性。

4-Ethoxycarbonyl-3,5-dimethyl-2-cyclohexen-1-one was obtained in 95% yield via Robinson annulation of ethyl acetoacetate with acetaldehyde over anhydrous sodium carbonate. The Robinson annulation catalyzed by anhydrous sodium carbonate system was extended to diverse substrates. Under the catalysis of this system, both aliphatic aldehydes and aromatic aldehydes could be converted into corresponding disubstituted cyclohexenones. The cyclization product, 4-ethoxycarbonyl-3,5-dimethyl-2-cyclohexen-1-one could be almost quantitatively converted into key intermediate 3,5-dimethyl-2-cyclohexenone with 99% yield through saponification and decarboxylation. The targeting compound3,5-dimethylphenol was obtained by direct dehydrogenation aromatization of 3,5-dimethyl-2-cyclohexenone.The structures of product and intermediates were characterized by ~1HNMR and;CNMR. The total yield of3,5-dimethylphenol was 66% under the synthesis route established in this paper. This process was suitable for the synthesis of 3-methyl-5-propylphenol and had certain universality.