以6,8-二氯辛酸为原料,S-（-）-α-苯乙胺为拆分剂进行拆分反应得到R-（＋）-6,8-二氯辛酸;经酯化制得R-（＋）-6,8-二氯辛酸乙酯;后经硫化水解一步合成R-（＋）-α-硫辛酸。考察了投料比、溶剂、催化剂、温度等条件对产物收率、比旋光度的影响。结果表明：拆分反应较佳条件为n[S-（-）-α-苯乙胺]∶n（6,8-二氯辛酸）=0.45∶1,溶剂为乙酸乙酯;酯化反应较佳条件为催化剂为对甲苯磺酸,反应时间7 h;硫化反应较佳条件为温度为65℃;相转移催化剂用量0.4 g,总收率为44.3%。通过红外光谱、比旋光度、核磁共振等对产物和中间产物进行了表征。%R-（＋）-6,8-dichlorooctanic acid was obtained in chiral resolution of 6,8-dichlorooctanic acid by using chiral split agent S-（-）-α-phenylethylamine.R-（＋）-α-lipoic acid was synthesized by sulfuration and hydrolysis from R-（＋）-6,8-dichlorooctanic acid ethyl ester that was prepared through esterfication reaction.The conditions were investigated and the results showed that the yield and specific rotation were influenced by feed ratio,solvent,catalyst and reaction temperature.Proper experimental condition for chiral reaction was found as：n[S-（-）-α-phenylethylamine]∶n（6,8-dichlorooctanic acid）=0.45∶1, solvent was ethyl acetate.The optimal esterfication reaction conditions was found as：the catalyst was p-toluene sulfonic acid,reaction time 7 h.The optimum conditions of sulfuration reaction were found as：reaction temperature was 65 ℃,the amount of phase transfer catalyst was 0.4 g;The overall yield was 48.4%.The product and intermediate were characterized by IR,specific rotation and 1H NMR.
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