N- vs O-protonation and the transannular substituent interaction in 8-(dimethylamino)-1-acetonaphthone

Dynamic NMR measurements of 8-(dimethylamino)-1-acetonaphthone 1 in neutral solutions reveal a solvent dependency of the barrier to NMe group intercha nge similar to that reported for N,N-dimethylacetamide. Titrating 1 with TF A in solvents of varying donicities gives rise to equilibrium mixtures of N -protonated aminoketone 2 and the O-protonated transannular addition produc t 3, the interconversion rate of which is slow on the NMR time scale at amb ient temperature. The preference for O- or N-protonation is medium-dependen t, the amount of N-protonated 2 increasing with a decrease in the nucleophi licity of the solvent. The set of equilibria which govern the interconversi on of 2 and 3 in the titration mixtures are identified and their equilibriu m 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 distrib ution of 2 and 3, paired with the tetrafluoroborate anion, depends on both the nucleophilicity and the polarity of the solvent. In PhNO2 the enthalpy change 3 --> 2 amounts to 2.6 kcal/mol.