Symmetry Analysis in Mechanistic Studies of Nucleophilic Substitution and β-Elimination Reactions

A mechanistic study of the bimolecular nucleophilic substitution (SN2) reaction for halomethane CH3X (X = Cl, Br, or I) is approached by using symmetry principles and molecular orbital theory. The electrophilicity of the functionalized sp–carbon is attributable to a 2p-orbital-based antibonding MO along the C–X bond. This antibonding MO, upon accepting an electron pair from a nucleophile, gives rise to dissociation of the C–X bond and formation of a new Nuc–C bond. Correlations are made between the molecular orbitals of reactants (Nuc and CH3X) and products (NucCH3 and X ). Similar symmetry analysis has been applied to mechanistic study of the bimolecular β-elimination (E2) reactions of haloalkanes. It well explains the necessity of an anti-coplanar arrangement of the Cα–X and Cβ–H bonds for an E2 reaction (anti-elimination). Having this structural arrangement, the bonding Cα–X (σC-X) and antibonding Cβ–H (σC-H) orbitals become symmetry–match. They can partially overlap resulting in increase in electron density in σC-H, which weakens and polarizes the Cβ–H bond making the β-H acidic. An E2 reaction can readily take place in the presence of a base. The applications of symmetry analysis to the SN2 and E2 reactions represent a new approach to studying organic mechanisms.