First-principle predictions of basicity of organic amines and phosphines in acetonitrile

Amines and phosphines are widely utilized as bases and basic organocatalysts in organic chemistry. Thus it is highly valuable to develop a coherent theoretical method that can accurately predict the basicity of structurally unrelated amines and phosphines in organic solvents from the first principles. Herein we developed the first ab initio protocol that could predict the pK(a) value of any protonated amine or phosphine in acetonitrile through systematic benchmarking. By comparing to a variety of available experimental data (total number=98), it was determined that the precision of the optimized method in basicity prediction was as low as 1.1 pK(a) unit. With the powerful new method in hand, we subsequently conducted some systematic studies about the basicity of organic amines and in particular phosphines, for which very few experimental data were available. It was found that the solvent exerted profound effects on the basicity of amines and phosphines. Accordingly we concluded that it was not valid to use gas-phase data to interpret the solution-phase basicity of amines and phosphines. Next we reported the basicity of a number of synthetically important aliphatic and aromatic amines and phosphines in acetonitrile. We also compared, for the first time, the alpha-substituent effects on the basicity of aliphatic amines and phosphines and the remote substituent effects on the basicity of aromatic amines and phosphines. Finally, we studied for the first time the basicity of cyclic amines and phosphines. It was found that the ring strain exerted some interesting effects on the basicity of amines and phosphines. (c) 2006 Elsevier Ltd. All rights reserved.