Lipophilic (Hydroxy)phenylacetates by Solvent-Free Lipase-Catalyzed Esterification and Transesterification in Vacuo

Abstract

Various long-chain alkyl (hydroxy)phenylacetates were prepared in high yield by lipase-catalyzed transesterification of the corresponding short-chain alkyl hydroxyphenylacetates and fatty alcohols in equimolar ratios. The reactions were performed in vacuo at moderate temperatures in the absence of solvents and drying agents in direct contact with the reaction mixture. Immobilized lipase B from Candida antarctica (Novozym 435) was the most effective biocatalyst for the various transesterification reactions. Generally, Novozym 435-catalyzed transesterifications of short-chain alkyl (hydroxy)phenylacetates with long-chain alcohols led to higher conversions and enzyme activities than the corresponding esterifications. For example, the transesterification activity was up to 4-fold higher than the esterification activity for the formation of oleyl 4-hydroxy-3-methoxyphenylacetate using Novozym 435 as a biocatalyst. The relative transesterification activities were as follows: phenylacetate > 3-methoxyphenylacetate approximately 4-methoxyphenylacetate > 4-hydroxy-3-methoxyphenylacetate > 3-hydroxyphenylacetate approximately 4-hydroxyphenylacetate >> 2-methoxyphenylacetate >> 3,4-dihydroxyphenylacetate. With respect to the position of methoxy and hydroxy substituents, the transesterification activity of Novozym 435 decreased in the order meta approximately para >> ortho. Compounds with inverse chemical structures, for example, tyrosyl oleate, were obtained by Novozym 435-catalyzed esterification and transesterification of fatty acids and their methyl esters, respectively, with 2-phenylethan-1-ols. In contrast to the transesterifications of short-chain alkyl (hydroxy)phenylacetates with fatty alcohols, higher conversions and enzyme activities were observed for the Novozym 435-catalyzed esterifications of (hydroxy)phenylethanols with long-chain fatty acids than the corresponding transesterifications with fatty acid methyl esters.