Study On A High-selective Synthesis Of Para-methoxyphenylacetic Acid

Para-methoxyphenylacetic acid used for important pharmaceutical and organic intermediates was effectively synthesized of an excellent regioselectivity instead of the traditional synthetic method of poor atom efficiency and environmental pollution. For the processes para-methoxyacetophenone as an intermediate based on the Friedel-Crafts reaction for anisole with acetic anhydride or acetyl chloride further react with sulfur and morpholine by a Willgerodt-Kindler rearrangement in the presence of various catalysts towards final product.The novel process was carefully discussed for industrial application. Friedel-Crafts para-acylation involved para-methoxyacetophenone intermediate preparation was highly controllable. Acylating agents, acetic anhydride and, appear good behavior on various catalysts. A 94.4% of high para-selection was achieved over 99% of anisole complete substrate conversion using acetyl chloride over zinc oxide under mild conditions, and 91% of para-isomer for acetic anhydride over zinc chloride in substrate conversion of 93.1% at warmer reaction temperature.Willgerodt-Kindler rearrangement was discussed used for the reaction of para-methoxyacetophenone with sulfur and morpholine towards para-methoxyphenylacetic acid via a precursor compound. A yield of 53.1% para-methoxyphenylacetic acid was obtained by using tetrabutyl ammonium bromide as a phase-transfer catalyst under water medium, keep the consistence of sodium hydroxide at 30%, reflux for 6 hours.