Issue Date: June 19, 2017
Modeling reduces nickel needed in catalytic reactions
Nickel catalysts are much less expensive than precious metal catalysts, but the large amounts of nickel catalyst used in many catalytic cross-coupling reactions still discourage industrial adoption. Over roughly the past two years, the vast majority of newly reported nickel-catalyzed cross-coupling reactions required 5 to 20 mole % of nickel catalyst. Neil K. Garg of the University of California, Los Angeles, grad student Nicholas A. Weires, and colleague Daniel D. Caspi of AbbVie have now collaborated to develop a technique that reduces loading (mole percent of catalyst required) in nickel-catalyzed amide esterifications (ACS Catal. 2017, DOI: 10.1021/acscatal.7b01444). They used a kinetic-modeling program, DynoChem, to assess the effect of several variables—ligand-to-metal ratio, reactant stoichiometry, product and by-product generation rate, catalyst temperature-equilibration time, catalyst loading, and reaction concentration—on the rate of benzamide-menthol esterification. They then used the data to develop a kinetic model for the reaction. Use of the model to optimize conditions reduced the 10 mole % nickel catalyst typically required in amide esterifications down to 2 mole %. And using it to tweak a specific benzamide-menthol esterification reduced the reaction’s nickel loading to as little as 0.4 mole %. The researchers hope the approach will help expand industrial use of nickel-catalyzed reactions and the use of kinetic modeling for reaction optimization.
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