Grignard reagents in solution: theoretical study of the equilibria and the reaction with a carbonyl compound in diethyl ether solvent.

The equilibria of Grignard reagents, CH3MgCl and CH3MgBr, in diethyl ether (Et2O) solvent as well as the reaction of the reagents with acetone are studied theoretically. To describe the equilibria and reactions in Et2O solvent, we employ the reference interaction site model self-consistent field method with the second-order Møller-Plesset perturbation (RISM-MP2) free energy gradient method. Since the solvent molecules strongly coordinate to the Grignard reagents, we construct a cluster model by including several Et2O molecules into the quantum mechanical region and embed it into the bulk solvent. We propose that, instead of the traditionally accepted cyclic dimer, the linear form of dimer is as stable as the monomer pair and participates in the equilibria. For the reaction with acetone, two important reaction paths (i.e., monomeric and linear dimeric paths) are studied. It is found that the barrier height for the monomeric path is much higher than that for the linear dimeric path, indicating that the reaction of the Grignard reagent with acetone proceeds through the linear dimeric reaction path. The change of solvation structure during the reaction is examined. On the basis of the calculated free energy profiles, the entire reaction mechanisms of the Grignard reagents with aliphatic ketones in Et2O solvent are discussed.