A thermodynamic study of ketoreductase-catalyzed reactions 4. Reduction of 2-substituted cyclohexanones in n-hexane

Abstract

The equilibrium constants K for the ketoreductase-catalyzed reduction reactions (2-substituted cyclohexanone + 2-propanol = cis- and trans-2-substituted cyclohexanol + acetone) have been measured in n-hexane as solvent. The 2-substituted cyclohexanones included in this study are: 2-methylcyclohexanone, 2-phenylcyclohexanone, and 2-benzylcyclohexanone. The equilibrium constants K for the reactions with 2-methylcyclohexanone were measured over the range T = 288.15 to 308.05 K. The thermodynamic quantities at T = 298.15 K are: K = (2.13 ± 0.06); Δ r G m ∘ = - ( 1.87 ± 0.06 ) kJ · mol - 1 ; Δ r H m ∘ = - ( 6.56 ± 2.68 ) kJ · mol - 1 ; and Δ r S m ∘ = - ( 15.7 ± 9.2 ) J · K - 1 · mol - 1 for the reaction involving cis-2-methylcyclohexanol, and K = (10.7 ± 0.2); Δ r G m ∘ = - ( 5.87 ± 0.04 ) kJ · mol - 1 ; Δ r H m ∘ = - ( 2.54 ± 1.8 ) kJ · mol - 1 ; and Δ r S m ∘ = ( 11.2 ± 6.4 ) J · K - 1 · mol - 1 for the reaction involving trans-2-methylcyclohexanol. The standard molar Gibbs free energy changes Δ r G m ∘ for the reactions ( trans-2-substituted cyclohexanol = cis-2-substituted cyclohexanol) in n-hexane have also been calculated and compared with the literature data that pertain to reactions in the gas phase and at higher temperatures. Experiments carried out with a chiral column demonstrated that the enzymatic reduction of 2-phenylcyclohexanone catalyzed by the ketoreductase used in this study is not stereoselective.