Steric activation in prototropic reactions of pyrazine derivatives. I. Polar and conformational effects

Abstract

The rates of proton loss from methyl groups in a number of pyrazine derivatives have been measured in D2O by monitoring the replacement of protium by deuterium at the acidic sites of the substrates; they include the reaction of four methylpyrazines with NaOD/D2O and nine alkylpyrazinium ions with D2O/DCl. The reactive site, which is a methyl group conjugated to the aza or azonium group of the substrate, is in all cases activated by an adjacent alkyl group, with the greatest effect, a factor of about 30, occurring when a proton on nitrogen is replaced by a methyl group. The phenomenon is analysed in terms of polar effects, ring strain and inter-alkyl interactions (including gear effects), and hybridization changes at nitrogen.