Research On The Synthesis Process Of2-(4-hydroxyphenyl)Ethanol

In recent years, metoprolol is the first medicine in treating cardiovascular diseases, and more attention has been paid to the synthesis process of2-(4-hydroxy-phenyl) ethanol, which is the key intermediate of metoprolol.In this dissertation, the synthesis process of2-(4-hydroxyphenyl) ethanol was improved and optimized based on the classical Six-step method as follows:1. In the synthetic process of phenethyl acetate, used high efficient catalyst, acetic anhydride as esterifying agent, and instead of aromatics, dichloroethane was first choosen as solvent of esterification of phenethyl alcohol, the molar yield was94.3%.2. Dichloroethane solvent method was first used for the nitration of phenethyl acetate, improved the ratio of p/o nitro compounds and reduced the dosages of fuming nitric acid and concentrated sulfuric acid greatly. Holding reaction temperature-5℃for1hour, n (fuming nitric acid):n (phenethyl acetate)=1.15:1, the molar yield of2-(4-nitrophenyl) ethanol reached80.1%.3. Using the same solvent system for hydrolysis and deoxidation, realized hydrolysis deoxidation One-pot method for the systhesis of2-(4-aminophenyl) ethanol, simplified the process greatly, and improved the total yield. Choosing the low-cost FeCl3as catalyst for hydrazine hydrate deoxidating2-(4-nitrophenyl) ethanol, the molar yield reached91.2%.4. Hexone was first choosen as solvent, copper sulfate as catalyst, realized the diazotization hydrolysis One-pot method for the systhesis of2-(4-hydroxyphenyl) ethanol, reduced the dosages of concentrated sulfuric acid and catalyst copper sulfate greatly. Using organic solvent extraction system-applying, the molar yield increased to90.6%. The product structure was identified with melting point and GC-MS, the HPLC purity of product was99.70%.5. Through the esterification, nitrification, hydrolysis, deoxidation, diazotization and hydrolysis six-step reactions, the total mole yield of2-(4-hydroxyphenyl) ethanol reached60.2%, much higher than the literature value24.0%.Then, the systhesis process of2-(4-hydroxyphenyl) ethanol through esterification of4-hydroxyphenylacetic acid, deoxidation in KBH4-ZnCl2system was improved and optimized, the molar yield of esterification was89.5%, the molar yield of deoxidation was75.3%, the HPLC purity of product was only96.11%. Compared the advantages and disadvantages of two synthesis process of2-(4-hydroxyphenyl) ethanol, the synthesis process of phenethyl alcohol has great industrialized application value.Finally, the kinetics of nitration of phenethyl acetate by mixed acid in the dichloroethane was studied. Established the first order kinetic model of nitration, obtained the equation of concentration change of phenethyl acetate and nitro phenethyl acetate, and deduced the apparent reaction rate constant k at different temperature. The apparent activation energy of nitration was115.43kJ.mol-1, and the apparent pre-exponential factor1nA was45.4547s-1.