Hydrogen Bonding of N-Heterocyclic Carbenes in Solution: Mechanisms of Solvent Reorganization

The hydrogen-bond dynamics of N-heterocyclic carbenes plays a central role in their proton-transfer reactions, and the effects of hydrogen bonding are also often invoked in corresponding organocatalytic applications. In the present study, the structures and lifetimes of hydrogen bonds have been investigated for several carbenes in alcohol-containing solutions by classical molecular dynamics simulations. The basicity of the carbene was found to be of major importance; while the least basic carbenes are often in their free form in the solvent, by increasing the basicity the simulations show increased hydrogen bonding, often even with two alcohol molecules at a time. In the latter structure the single lone pair of the carbene is in interplay with two hydrogen bond donors. The exchange mechanism is different for carbenes with different basicities, with different substituents, and in different solvents, occurring through the free carbene for the least basic compounds, and through the aforementioned doubly-hydrogen-bonded structure in case of the most basic derivatives. Since this process plays a central role also in H/D exchange reactions, we argue that the pK values calculated from the related measurements have a varying physical meaning for the different carbenes. The lifetimes of the hydrogen bonds are apparently also clearly related to the basicity of the carbene, with gradually increasing lifetimes for the most basic compounds.