Stepwise versus Concerted: Theoretical Insights into the Stereoselectivity in Aryl Imine Formation Assisted by Acid and Water

Abstract

The wide applications of the aryl Schiff base require extensive understanding of the mechanism of its formation, which remains unclear. In this work, the detailed formation mechanisms between benzaldehyde and aniline or 4-(9-anthryl) ethynyl aniline were investigated at the CCSD(T)//B3LYP level, and the influence of water molecules and acid catalysis and the stereoselectivity were addressed. The results show that the participation of explicit water molecules greatly accelerates the reactions by alleviating the ring tension of the transition states, and acid catalysis strongly favors the imine formation and provides driving force for the forward reaction. In acidic conditions, both N-protonated carbinolamine formations and imine formations are achieved under mild conditions with the assistance of water molecules, and the proton transfer is more advanced than the C−N and C�N bond formation, which is in good agreement with the experimental observations. In contrast, under neutral conditions, even with the assistance of two water molecules, the reaction is hard to take place at room temperature owing to the high Gibbs free energy barriers with the proton transfer and the C−N or C�N bond formation concerted. The analysis of stereoselectivity shows that the formation of trans imine is both kinetically and thermodynamically more favorable than the cis one under the acidic condition with the assistance of water molecules, and the presence of conjugated substituent 4-(9-anthryl) ethynyl of aniline marginally raises the energy barriers. This work provides a systematic view of the mechanism for the formation of aryl imine and is expected to offer insights for the control of the dynamic covalent chemistry and the synthesis of covalent organic frameworks.

Mechanism and Origin of Stereoselectivity of N-Heterocyclic Carbene (NHC)-Catalyzed Transformation Reaction of Benzaldehyde with o-QDM as Key Intermediate: A DFT Study

“…Thus, identifying the key factors that govern stereoselectivity is also interesting and informative. With theoretical investigation on the mechanism of NHC-catalyzed reactions at the core of the research activity in our group, − we now employ a theoretical investigation on the mechanism of NHC-catalyzed activation/transformation of 9 H -fluorene-1-carbaldehyde involving an o -QDM intermediate as key intermediate using the density functional theory (DFT) method, which has frequently used for mechanistic investigation of organocatalytic − and organometallic reactions. − …”