(1R,2R)-1,2-环己烷二甲醇二甲磺酸酯的合成

Synthesis of(1R,2R)-1,2-dimethyl Cyclohexane Dimethanol Sulfonate

目的:合成(1R,2R)-1,2-环己烷二甲醇二甲磺酸酯(化合物1)。方法:以(±)-反式-4-环己烯-1,2-二甲酸(化合物2)为原料,经钯碳还原、(R)-1-苯乙胺拆分、在甲醇中与氯化亚砜反应、硼氢化钠-无水氯化锂还原、甲基磺酰氯反应得到目标化合物,并进行核磁共振(1H-NMR)或质谱(MS)表征。以(1R,2R)-1,2-环己烷二甲酸(化合物4)/氯化亚砜的投料比、反应温度和时间对酰化反应进行优化,以化合物4/硼氢化钠/无水氯化锂的投料比、反应温度和时间、溶剂对酯还原反应进行优化,筛选(1R,2R)-1,2-环己烷二甲醇(化合物5)的合成条件。结果:表征确证目标化合物为化合物1,总收率为27.9%,纯度>99%。化合物5的合成中,酰化反应条件为化合物4/氯化亚砜投料比为1.0:2.2,反应温度为65℃,反应时间为2h;酯还原反应条件为化合物4/硼氢化钾/无水氯化锂投料比为1.0:3.0:3.0,反应温度为20～30℃,反应时间为24h,溶剂为四氢呋喃。结论:所建立的反应条件温和、操作简便易行,各步原料价格低廉。

OBJECTIVE：To synthetize（1R,2R）-1,2-dimethyl cyclohexane dimethanol sulfonate（compound 1）.METHODS：The target compound was synthesized from trans-4-cyclohexene-1,2-dicarboxylic acid（compound 2）,through reduced by Pd/C,separated by（R）-1-phenethylamine,reacted with thionyl chloride in methanol,reduced by sodium borohydride-anhydrous lithium chloride and then reacted with methylsufonyl chloride.The target compound was characterized by MS or 1 H-NMR.The acylation reaction was optimized by ratio of thionyl chloride to（1R,2R）-1,2-cyclohexane dicarboxylic acid（compound 4）,reaction temperature and reaction time.The ester reduction reaction was optimized by ratio of compound 4 to sodium borohydride to anhydrous lithium chloride,reaction temperature and time,solvent.The synthesis condition was screened for（1R,2R）-1,2-cyclohexane dimethanol（compound 5）.RESULTS：The target compound was confirmed as compound 1,with total yield of 27.9% and purity of 99%.The synthesis condition of compound 5 was as follows：acylation with ratio of compound 4 to thionyl chloride as 1.0：2.2,reaction temperature of 65 ℃,reaction time of 2 h;ester reduction with ratio of compound 4 to potassium borohydride to anhydrous lithium chloride as 1.0：3.0：3.0,reaction temperature of 20-30 ℃,reaction time of 24 h,solvent of diethylene oxide.CONCLUSIONS：The synthesis process is mild in reaction conditions and simple in operation.Raw materials of each step cost less.