Study On Synthesis Of 6-hydroxy-8-chlorooctanoic Acid Ethyl Ester

Ethyl 6-hydroxy-8-chlorooctanoate is an important organic intermediate and is currently mainly used for the synthesis of certain drugs and intermediates of drugs,in particular the synthesis of alpha-lipoic acid drug intermediates.In recent years,due to the medically important value of alpha-lipoic acid,scientists are increasingly interested in the synthesis of its intermediate 6-hydroxy-8-chlorooctanoic acid,but there are few literatures on the synthesis of 6-hydroxy-8-chlorooctanoic acid at home and abroad.Under the entrustment of Sanmenxia Aoke Chemical Co.,Ltd.,we conducted a study on the preparation of ethyl 6-hydroxy-8-chlorooctanoate.The main contents of this paper's research are as follows:?1?Synthesis of ethyl 6-oxo-6-chlorohexanoate using ethyl adipate as raw material.The effects of molar ratio,reaction temperature,reaction time and other factors on the preparation of 6-oxo-6-chlorohexanoic acid ethyl ester as the first step target product were investigated through single-factor experiments.The superior technological conditions were obtained:n?thionyl chloride?:n?ethyl adipate?=1.6:1,the reaction temperature is 60?,the reaction time is 2 h,and the content of ethyl6-oxo-6-chlorohexanoate reaches the maximum;Further optimization of the process conditions was carried out by orthogonal experiments.The best combination of levels was n?thinyl chloride?:n?ethyl adipate?=1.6:1,and the reaction temperature was65?.The time was 1.5 h,and the experiment was repeated 3 times under the optimized conditions.The average content was 95.24%.The target product was determined by nuclear magnetic resonance spectroscopy.The content of each component in the reaction solution was analyzed by gas chromatographic area normalization.?2?Synthesisofethyl6-oxo-8-chlorooctanoatefromsynthesized6-oxo-6-chlorohexanoic acid ethyl ester.The effect of the amount of catalyst,reaction temperature,reaction time and other factors on the preparation of the6-oxo-8-chlorooctanoic acid ethyl ester of the second step product was investigated by single factor experiments,and the optimum process condition was obtained n?AlCl₃?:n?ethyl 6-oxo-6-chlorohexanoate?=2.1:1,the reaction temperature was10?,the aeration time was 2.5 h,and the content of ethyl 6-oxo-8-chlorooctanoate reached the maximum.The target product was determined by nuclear magnetic resonance spectroscopy.The content of each component in the reaction solution was analyzed by gas chromatographic area normalization.?3?Preparation of ethyl 6-hydroxy-8-chlorooctanoate from synthesized6-oxo-8-chlorooctanoic acid ethyl ester.The single factor experiment was used to examine the effect of reaction temperature on the experimental results.The optimum process conditions were obtained,namely the reaction temperature was 10?,and the content of ethyl 6-hydroxy-8-chlorooctanoate reached the highest.The target product was determined by infrared spectroscopy,nuclear magnetic resonance spectroscopy and carbon spectroscopy.The content of each component in the reaction solution was analyzed by gas chromatographic area normalization.?4?The amount of water used for the post-treatment of the reaction liquids of6-oxo-8-chlorooctanoic acid ethyl ester and ethyl 6-hydroxy-8-chlorooctanoate was optimized,and the optimal water consumption was obtained,which was respectively0.8 L,0.85 L.