Computational Organic Chemistry. Rates and equilibria of organic reactions, including aldol and Claisen condensations and Michael reactions. Calculation of rate constants by No Barrier Theory
Tradational Division: Organic
B.Sc., University of Western Ontario; Ph.D. Harvard
I have found a way to predict the absolute rate constants for chemical reactions in solution by a quite general method which seems intuitively reasonable and is computationally facile, at least in many cases. This method involves no adjustable parameters, and requires no input of kinetic information.
The fundamental idea is that the kinetic barrier to a chemical reaction arises because of the need to have several things (molecular events) occur simultaneously in order for the reaction to take place. If only one thing had to happen then there would be no barrier and the energy would be a simple quadratic function of the extent of progress along the reaction coordinate. Because most real reactions require two or more processes, each associated with a quadratic barrier, in order to give the overall transformation, the overall process is seen to have a barrier.
This model permits calculation of the barrier if the energy changes for the simple processes can be estimated. For many classes of reaction this is possible, and for the cases examined so far the method leads to good approximations to the observed free energies of activation. Computational methods are now sufficient to allow free energy changes to be calculated using molecular orbital theory.
I propose to apply the method to a selection of reactions, ultimately covering all of chemistry, to test whether it is indeed general and reliable. For this to be practical requires developing computer programs to automate the process.
This research will have an impact on many areas of chemistry and enzymology, and will lead to methods providing useful guidance to synthetic chemists, both academic and industrial.