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以六氢苯酐为原料,采用顺反异构化反应合成反式-1,2-环己烷二甲酸;然后,选用较为廉价的R-(+)-α-甲基苄胺(R-PEA)作为拆分剂,通过手性拆分、酸化合成(1R,2R)-反式环己烷二甲酸。探讨了催化剂种类、反应温度和反应时间对产品顺反式比例的影响;同时考察了溶剂种类和用量对手性拆分效果的影响。反式-1,2-环己烷二甲酸的最优合成工艺条件为:硫酸为催化剂,反应温度120℃以上,反应时间12 h左右,在该反应条件下产品收率为80%;采用1HNMR测定了产物中反式质量分数为99.3%;最佳手性拆分条件为:甲醇作溶剂,n(反式-1,2-环己烷二甲酸)∶n(R-PEA)=1∶1,每10 g反式-1,2-环己烷二甲酸加入30 mL甲醇,在该反应条件下(1R,2R)-反式环己烷二甲酸·(R)-PEA盐的收率可达38%;经过酸化后得到(1R,2R)-反式环己烷二甲酸,酸化收率为85%;采用手性柱HPLC测定了目标产物的光学纯度(ee值)为98.48%。
Trans-1,2-cyclohexanedicarboxylic acid was synthesized by cis-trans isomerization using hexahydrophthalic anhydride as the starting material. Then, the more inexpensive R - (+) - α-methylbenzylamine ) As a resolving agent, (1R, 2R) -transcyclohexanedicarboxylic acid was synthesized by chiral resolution and acidification. The effects of catalyst type, reaction temperature and reaction time on the cis-trans ratio of the product were discussed. The effects of solvent type and amount on the chiral resolution were also investigated. The optimal synthesis conditions of trans-1,2-cyclohexanedicarboxylic acid were as follows: sulfuric acid as catalyst, reaction temperature above 120 ℃, reaction time about 12 h, the yield of product under the reaction conditions was 80%; 1HNMR The trans-1, 2-cyclohexanedicarboxylic acid: n (R-PEA) = 1: 1, the yield of (1R, 2R) -transcyclohexane dicarboxylate · (R) -PEA salt was added to 10 mL of trans-1,2-cyclohexanedicarboxylic acid per 10 g of methanol (1R, 2R) -transcyclohexane dicarboxylic acid was obtained after acidification, the yield of acidification was 85%. The optical purity (ee value) of the target product was determined to be 98.48% by chiral column HPLC.