Method to search the most stable reaction path and show the results applying to the Pinner Pyrimidine reaction

Abstract

The development of synthetic routes for functional chemicals has been heavily depending on experience and intuition of synthetic organic chemists. In case that desired molecules have complex structures, there are many possible synthetic routes, and it is often difficult to determine which one should be adopted. For reactions of molecules with many substituents, we have proposed a method to locate the TS structure of a target reaction by using TS structures of similar reactions stored in TSDB. However, this method seldom gives the most stable TS structure within possible conformers. That is, the stability of optimized transition states (TS), reactants and products is highly dependent on initial structures used for optimization. Therefore, this method is likely to give inadequate data to compare calculated and measured values of other synthetic reactions. For these purposes, we have to find reaction mechanism with the most stable TS and molecules involved in the reaction. In this paper, we proposed a method to search the most stable reaction path and show the results applying to the Pinner Pyrimidine reaction of 1-phenylbutane-1,3-dione and ethanimidamide.