title: N- vs O-protonation and the transannular substituent interaction in 8-(Dimethylamino)-1-acetonaphthone
abstract: Dynamic NMR measurements of 8-(dimethylamino)-1-acetonaphthone 1 in neutral solutions reveal a solvent dependency of the barrier to NMe group interchange similar to that reported for N,N-dimethylacetamide. Titrating 1 with TFA in solvents of varying donicities gives rise to equilibrium mixtures of N-protonated aminoketone 2 and the O-protonated transannular addition product 3, the interconversion rate of which is slow on the NMR time scale at ambient temperature. The preference for O- or N-protonation is medium-dependent, the amount of N-protonated 2 increasing with a decrease in the nucleophilicity of the solvent. The set of equilibria which govern the interconversion of 2 and 3 in the titration mixtures are identified and their equilibrium constants evaluated from the NMR data. X-ray analysis of the crystalline trifluoroacetate salt of O-protonated 3 indicates that the transannular N.CO bond of 3 is formed to an extent of only 80%. The equilibrium distribution of 2 and 3, paired with the tetrafluoroborate anion, depends on both the nucleophilicity and the polarity of the solvent. In PhNO(2) the enthalpy change 3 --> 2 amounts to 2.6 kcal/mol.
authors.affiliation: Department of Chemistry, Pennsylvania State University, Abington College, Abington, Pennsylvania 19001 and the Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, USA.
authors.initials: II
authors.lastname: Schuster
authors.initials: AJ
authors.lastname: Freyer
authors.initials: AL
authors.lastname: Rheingold