Kinetic and thermodynamic analysis for lipase-catalyzed hydrolytic resolution of (R,S)-alcohols though their azolyl carbamates

A new approach to the lipase-catalyzed hydrolytic resolution of (R,S)-azolyl carbamates for obtaining chiral azolyl carbamates and alcohol is described. With (R,S)-1-phenylethyl azolyl carbamates as the model substrates, the best reaction condition of using (R,S)- 1-phenylethyl 4-bromopyrazole carbamate (1) as the substrate in water-saturated diisopropyl ether at 45 °C is selected. The kinetic constants, and hence enantiomeric ratio of 124, are then estimated from the kinetic analysis by considering the alcohol inhibition effect, with which theoretical time-course conversions for both enantiomers are numerically solved and agree with the experimental data. The thermodynamic parameters -δδH and -δδS satisfying a linear enthalpy-entropy compensation relationship of -δδS = -38.84 + 3.29(-δδH) are further estimated. An extension of the resolution platform to (R,S)-4-bromopyrazole carbamates derived from other (R,S)-alcohols (4, 5, 7) is also addressed.