AN AM1 calculational study of the protonation and reactions of 3,4-dihydro-2-oxo-1,4-ethanoquinoline, 3,4-dihydro-2-oxo-1,4-propanoquinoline, 3,3,4,5-tetrahydro-2-oxo-1,5-ethanobenzazepine, 3,3,4,5-tetrahydro-2-oxo-1,5-propanobenzazepine, and N-methyl-4-bromo-2-methylacetanilide

The gas phase N- and O-protonation of distorted amides 3,4-dihydro-2-oxo-1,4-ethanoquinoline (1a), 3,4-dihydro-2-oxo-1,4-propanoquinoline (1b), 3,3,4,5-tetrahydro-2-oxo-1,5-ethanobenzazepine (1c), and 3,3,4,5-tetrahydro-2-oxo-1,5-propanobenzazepine (1d) and normal amides 4-bromo-2,N-dimethylacetanilide (5a) and 2,N-dimethylacetanilide (5b), along with the N-protonation of benzoquinuclidine (7), has been studied calculationally at the semiempirical level of theory with AM1. Calculated enthalpies of N- and O-protonation (proton affinities) indicate that 1a, 1b, and 1c should protonate on nitrogen and 1d, 5a, and 5b on oxygen. A satisfactory straight-line relationship between the calculated proton affinities of 1a, 1b, 1c, and 7 with experimental solution pK(a)'s is used to estimate the solution pK(a) of 1d. Results of a calculational study on the gas phase N- and O-methylation of 1b, 1c, and 1d are nicely in accord with the findings of an experimental solution phase study of the methylation-hydrolysis of 1b and 1d: while 1b methylates on nitrogen, 1d methylates on oxygen. A calculational study of possible pathways of hydrolysis of the N-protonated amides indicates that solvolysis of the hydrates of these species represents a viable route for their conversion to ring-opened products.