The effect of microsolvation on the mechanism, kinetics and energetics of a reductive amination reaction
File(s)
Author(s)
Diamanti, Aikaterini
Galindo, Amparo
Adjiman, Claire S
Type
Journal Article
Abstract
The reductive amination of carbonyl compounds is widely employed to synthesize functionalized amines in solution. The presence of water is known to impact the reaction rate but the underlying phenomena are poorly understood. Here, we combine nuclear magnetic resonance spectroscopy and quantum mechanical (QM) calculations to elucidate the effect of microsolvation on the mechanism, kinetics and energetics of the reaction between benzaldehyde and 4-(trifluoromethyl)-aniline in tetrahydrofuran. Kinetic data with varying water content indicate an autocatalytic effect. We explain this process by including two water molecules in QM calculations, demonstrating the transition-state stabilization that results from hydrogen bond formation. Through an extensive investigation of different QM methods, we find a “high-low” computational scheme with the G2MP2 method and SMD solvation model yields good quantitative agreement with experimental evidence, providing a theoretical approach to accelerate the development of other reductive amination reactions.
Date Issued
2025-05-21
Date Acceptance
2025-03-31
Citation
Industrial & Engineering Chemistry Research, 2025, 64 (20), pp.9867-9880
ISSN
0888-5885
Publisher
American Chemical Society
Start Page
9867
End Page
9880
Journal / Book Title
Industrial & Engineering Chemistry Research
Volume
64
Issue
20
Copyright Statement
© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY 4.0 .
License URL
Subjects
1-DODECENE
ACID
Engineering
Engineering, Chemical
GAUSSIAN-2 THEORY
HYDROFORMYLATION
HYDROGEN
MODELS
ROUTE
Science & Technology
SOLVENT
Technology
Publication Status
Published
Date Publish Online
2025-05-07