1H and13C NMR spectra of α-heterocyclic ketones and assignment of keto, enol and enaminone tautomeric structures

Abstract

A method for distinguishing enol and enaminone tautomers of acylmethyl heterocycles is described based on differences in 13C chemical shift between the carbonyl carbon atom of the enaminone (CO) and enolic carbon atom of the enol (C–OH). For 2-, 3- and 4-acetylmethyl, -phenacyl, and -pyridacyl-pyridines, -pyrazines, -quinolines, -quinoxalines, -phenanthrolines. -benzoxazoles and -benzothiazoles (usually in CDCl3 as solvent) measured values of δc fall in the non-overlapping ranges 179–191 ppm for the enaminones and 161–171 for the enols. Both sets of chemical shifts depend on the electronegativity of the acyl substituent and for strongly electron-withdrawing groups, such as pyruvate, δc for the enaminone does overlap the range for the enol. However the difference in chemical shifts (Δδc∼ 20) appears to be nearly independent of substituent, and in these cases the value for the enaminone can be predicted from a correlation of δc with σ* for the acyl substituent based on data of Greenhill, Loghmani-Khouzani and Maitland (J. Chem. Soc., Perkin Trans.1, 1991, 2831) for substituted quinolines. No other proton or carbon chemical shift differentiates the tautomers, but the structural assignments are corroborated by (a) comparisons with N-methyl enaminone models for the enaminone tautomers, (b) coupling constants (J34) between 3- and 4-hydrogen atoms of pyridine and quinoline rings and (c) allylic coupling between CH3 and vinyl hydrogens in enols of methyl ketones. With the exception of pyruvates, enols are observed only for 2-substituted heterocycles, usually as mixtures (in CDCl3) with the easily distinguished keto tautomers, but for (2-substituted) quinolines and quinoxalines the enaminone tautomer predominates. Structural assignments in aqueous media or other solvents where solubility precludes NMR measurements follow from correlations of UV–VIS with NMR spectra. NMR and UV–VIS measurements are considered in detail for the example of 2-phenacylpyridine.