Kinetics and mechanism of regioselective monoacetylation of 3-aryloxy-1,2-propandiols using immobilized Candida antarctica lipase

• Lipase catalyzed regioselective monoacetylation of 3-aryloxy-1,2-propanediol was studied in non-aqueous media.
• Immobilized Candida antarctica lipase B was found to be the best catalyst.
• The effect of different reaction parameters affecting reaction rate and conversion were discussed.
• The ternary complex mechanism with alcohol inhibition supports the reaction mechanism.

Optically pure 3-aryloxy-1,2-propanediols are important intermediates in the synthesis of various pharmaceutical compounds. This study reports the kinetics and mechanism of lipase catalyzed regioselective monoacetylation of 3-aryloxy-1,2-propandiols. Regioselective monoacetylation of 3-(2-methylphenoxy) propane-1,2-diol was chosen as a model reaction and various commercially available lipases were screened as catalysts. Candida antarctica lipase B (Novozyme 435) was found to be the best catalyst among all considering the yield and excess of monoacetylated product. Important reaction parameters were optimized systematically to improve the rate of reaction and conversion, viz., speed of agitation, reaction solvent, catalyst loading, reaction temperature and mole ratio. The study of initial rate and progress curve demonstrated that the reaction obeys the ternary complex mechanism and 3-(2-methylphenoxy) propane-1,2-diol inhibits the reaction at higher concentrations. Theoretical predictions and experimental rates match very well based on non-linear regression analysis. Under optimized reaction conditions the study was further extended to regioselective monoacetylation of a variety of 3-(aryloxy)-1,2-propanediols.

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