Lipase‐Catalyzed Synthesis of Substituted Phenylacetamides: Hammett Analysis and Computational Study of the Enzymatic Aminolysis. Issue 29 (4th September 2014)

• Record Type: Journal Article
• Authors: García Liñares, Guadalupe; Arroyo Mañez, Pau; Baldessari, Alicia
• Is Part Of: European journal of organic chemistry. Issue 29(2014)
• Page Start: 6439
• Page End: 6450
• Publication Date: 2014-09-04
• Subjects: Enzyme catalysis -- Molecular modeling -- Reaction mechanisms -- ­Amides -- Esters; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201402749
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: A series of hydroxy‐, methoxy‐, and nitrophenylacetamides was synthesized by enzyme catalysis. The 28 new products were obtained through a lipase‐catalyzed two‐step reaction in very good to excellent yield. In the case of nitro derivatives, a one‐pot, two‐step methodology allowed the desired products to be obtained in high yields. The influence of various reaction parameters in the lipase‐catalyzed reactions, such as enzyme source, nucleophile (alcohol or amine)/substrate ratio, enzyme/substrate ratio, solvent and temperature were studied. It was observed that nitro‐substituted phenylacetates were more reactive in the aminolysis reaction than phenylacetates substituted with a hydroxyl group. To study this substituent effect, a Hammett analysis and the determination of the ρ parameter were carried out. Moreover, a computational study was applied to the most representative systems, performing an exploration of the potential energy surface for the catalyzed and noncatalyzed aminolysis reaction for nitro‐ and hydroxyphenylacetates. Both analysis showed that the presence of a strongly electron‐attracting group favors the activity of the enzyme, in complete agreement with the experimental results of the enzymatic catalysis. Abstract : Substituted phenylacetamides were obtained from phenylacetic acid through lipase‐catalyzed esterification and aminolysis. The lipase activity in the aminolysis of phenylacetic esters depends on the substitution in the ring. 4‐Nitrophenylacetic acid afforded the corresponding amides in the highest yield in a one‐pot, two‐step procedure. Hammett analysis and a computational study were carried out.