Lipase-catalyzed enantioselective resolution of (R,S)-N-2-methylalkanoyl-3- (2-pyridyl)pyrazoles in organic solvents

Yi Sheng Lin, Pei Yun Wang, An Chi Wu, Shau Wei Tsai*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

15 Scopus citations

Abstract

The lipase-catalyzed resolution of (R,S)-pyrazolides containing a 2-aryl substituent to the α-chiral center has been successfully extended to (R,S)-N-2-methylalkanoyl-3-(2-pyridyl)pyrazoles (1-4) containing different alkanoyl-chain lengths. The best reaction condition for CALB-catalyzed hydrolysis of (R,S)-N-2-methylheptanoyl-3-(2-pyridyl)pyrazole (1) in water-saturated MTBE at 35 °C is selected, leading to an excellent enantioselectivity (VR/VS > 100) with improved initial specific activities in comparison with that of (R,S)-N-2-phenylpropionyl-3-(2- pyridyl)pyrazole. The thermodynamic analysis for the hydrolysis of 1 demonstrates great influences of water content and solvent hydrophobicity on varying the ehthalpic and entropic contributions in water-saturated and anhydrous MTBE and IPE, and leads to an excellent enthalpy-entropy compensation relationship ΔΔS = 3.113ΔΔH + 33.86 (r2 = 0.999). Moreover, a thorough kinetic analysis for all substrates indicates that a critical valeroyl-chain length for obtaining the enantiomer discrimination and improved lipase activity for the fast-reacting (R)-pyrazolide is needed.

Original languageEnglish
Pages (from-to)245-249
Number of pages5
JournalJournal of Molecular Catalysis B: Enzymatic
Volume68
Issue number3-4
DOIs
StatePublished - 03 2011

Keywords

  • (R,S)-N-2-methylalkanoyl-3-(2-pyridyl)pyrazoles
  • Alcoholysis
  • Hydrolysis
  • Kinetic and thermodynamic analysis
  • Lipases

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