Study On The Synthesis And Production Process Of P-Hydroxyphenylethyl Alcohol

p-Hydroxyphenylethyl alcohol is an important medicine intermediate widely used in the preparation of some useful drugs and perfumes. At present, the synthetic methods of p-hydroxyphenylethyl alcohol are not suitable for large-scaled industrial application due to the long synthetic route , low overall yield, rigorous reaction conditions and high cost. The product used at home mainly depends on import. Through the research herein, a novel method with high yield and low cost, which was easy to control was achieved, and it had great significance on developing the low-cost process of p-hydroxyphenylethyl alcohol.In this paper, p-hydroxyphenylacetic acid was used as raw material and two synthetic methods of p-hydroxyphenylethyl alcohol were discussed. One was directly reducing p-hydroxyphenylacetic acid to p-hydroxyphenylethyl alcohol, and the other was reducing p-hydroxyphenylacetate methyl to p-hydroxyphenylethyl alcohol after esterifying of p-hydroxyphenylacetic acid. Varieties of modified sodium borohydride and potassium borohydride systems were applied in the reduction for the first time and the reduction activity of them was systematically studied. The optimum conditions of reduction systems with better activity were studied by single factor analysis and process of the system with excellent activity was optimized by orthogonal experiments.NaBH4-I2,NaBH4-BF3·Et2O and NaBH4-diglyme reduction systems were studied in details when reducing p-hydroxyphenylacetic acid. The one with excellent activity was NaBH4-I2, the optimum synthesis conditions of which were as follows: n(NaBH4):n(p-hydroxyphenylacetic acid)=2:1, n(I2): n(p-hydroxyphenylacetic acid)= 0.75, the reaction temperature 30℃,the reaction time 6h. The yield was 76.1% and the purity was 98.4% under the optimum conditions.SOCl2 was chosen to react with p-hydroxyphenylacetic acid and methanol to synthesize p-hydroxyphenylacetate methyl. The optimum synthesis conditions of esterification were that: n(SOCl2):n(p-hydroxyphenylacetic acid)=1.2, n(p-hydroxyphenylacetic acid):n(methanol)=1:15, reaction temperature 35℃, reaction time 3h.Under these conditions, the yield was 86.3%and the purity was 98.7%. KBH4-H2O-CH3OH,KBH4-ZnCl2 reduction systems were studied in details in the reduction of p-hydroxyphenylacetate methyl. KBH4-ZnCl2 displayed high reduction activity and the optimum conditions were determined: n(KBH4):n(p-hydroxyphenylacetate methyl)=1.5:1, n(ZnCl2):n(KBH4)=1:1.5,reaction temperature 66℃(reflux), reaction time 6h. The yield was 82.7% and the purity was 98.4% under the optimum conditions.The reaction conditions of KBH4-ZnCl2 were mild and the process was simple. With less required reductant, low price of KBH4 and ZnCl2 and high yield, KBH4-ZnCl2 was an excellent reduction system in the preparation of p-hydroxyphenylethyl alcohol. Reducing p-hydroxyphenylacetate methyl to prepare p-hydroxyphenylethyl alcohol using KBH4-ZnCl2 represented good prospect in pilot experiment and industrial application.