Proton affinity of some substituted 2,6-dimethylbenzamides and their N,N-dimethyl derivatives:: the susceptibility of the amide group to polar substituent effects

The proton affinity (PA) of 2,6-dimethylbenzamide and its derivatives substituted by an amino or a nitro group at the para- or meta-position, as well as of the corresponding N,N-dimethylbenzamides, have been determined by the kinetic method using bracketing by a pair of reference bases B-i which give a slightly more or less intense signal of the protonated base [BHi](+) compared with that of the protonated amide [AH](+), The amide group of the 2,6-dimethylbenzamides is twisted out of the plane of the aromatic ring by the methyl substituents at both ortho-positions which interrupts the pi-electron conjugation between amide group and benzene ring. The amino group and the nitro group have been chosen as prototypical polar substituents with electron donating and with electron withdrawing properties to reveal the effect of steric hindrance of pi-conjugation on the PA of benzamides, A comparison with the PA of the corresponding sterically unhindered benzamides shows that this effect is generally small and manifests itself clearly only in the case of para-amino substituents. This result is discussed considering different conformations of the benzamides using semi-empirical PM3 calculation. The absolute PA values calculated by PM3 agree only modestly with the experimental values, but the calculated conformation and the relative PA values corroborate a weak interaction between amide group and benzene ring as suggested by experiments. Finally, the modest susceptibility of the amide group and protonated amide group to polar substituent effects in the gas phase agrees with comparable small substituent effects observed on the pK(a) in solution and shows that the amide group is singular with respect to a "resonance saturation".