Anionic substitution at carbonyl carbon. Implications for the chemistry of ions in solution

Abstract

AM1 calculations are reported for the reactions of seven anions (HO^–, MeO^–, EtO^–, NH₂^–, MeNH^–, OCHNH^–, H^–) with eight carboxylic derivatives (formic acid, the methyl esters of formic, acetic, fluoroacetic, difluoroacetic, and trifluoroacetic acids, formamide, and N-methylformamide) and formaldehyde. All were predicted to involve exothermic addition to the carbonyl group without activation, to form tetrahedral adducts, in agreement with our earlier work and recent ab initio calculations. The barriers to such reactions in solution are thus due entirely to the energy needed to desolvate the anion in order that the other reactant can approach. The nature and role of such desolvation barriers are discussed, with special reference to the hard–soft-acid–base theory and the mechanisms of enzyme reactions.