TRANSITION-STATE STRUCTURAL VARIATIONS IN THE MENSHUTKIN REACTION - A COMPUTATIONAL STUDY OF STERIC AND ELECTRONIC SUBSTITUENT EFFECTS

Transition structures for the gas phase S(N)2 reactions of substituted pyridines with methyl chloride, bromide, and iodide, respectively, have been localized by the AMPAC program using the AM1 Hamiltonian. The reactions are strongly endothermic (Delta E approximate to 40-60 kcal/mol) and have activation barriers of ca. 70 kcal/mol, and the calculated order of leaving group (X) abilities is I < Br < Cl. The carbon-nitrogen bond is longer for the more reactive leaving group. The structural parameters are relatively insensitive to substitutions in the pyridine ring. Increasing the steric strain in the ortho position (methyl to tert-butyl or 2,6-dimethyl) leads to looser and earlier transition states, whereas substitution with electron-withdrawing groups in the para position has very little effect on the transition structure. Solvent effects were briefly mimicked by means of a dipole placed on the N...C...X axis with the positive charge pointing toward X. This results in a decrease of the activation barrier, a less endothermic reaction, earlier transition state, and a larger negative charge on X. The consequences of steric effects in this reaction are discussed.