SIMULTANEOUS DETERMINATION OF PRIMARY AND SECONDARY THERMODYNAMIC ISOTOPE EFFECTS IN TAUTOMERIC EQUILIBRIA

NMR determination of site-specific hydrogen isotope ratios at natural deuterium abundance (SNIF-NMR) provides the basis for simultaneous acc ess to primary and secondary thermodynamic fractionation factors in ex change reactions and avoids the need for selective isotope labelling o f the reagents. The method was applied to the measurement of fractiona tion parameters involving OH, CH2, CH3 and =CH groups in keto-enol tau tomeric equilibria. The fractionation factors relating the =CH and OH sites of the enol species are simply derived from H-2 NMR spectra wher eas the determination of isotope parameters which relate keto and enol positions exploits a combination of H-2 and H-1 NMR experiments. Sinc e only monolabelled isotopomers have to be considered at natural abund ance, the method also offers the advantage of avoiding the occurrence of complex equilibria associated with multi-labelled species possibly introduced by deuterium enrichment. The primary equilibrium isotope ef fects illustrate a preference of deuterium for the methylene fragment of the keto form with respect to the ethylenic position of the enol ta utomer. Since the enol species is itself engaged in a fast tautomeric equilibrium associated with a symmetric or unsymmetric double minimum potential, the thermodynamic parameters are averaged over the exchangi ng partners. It is shown that the average thermodynamic fractionation factor relating the OH and =CH hydrogens of the enol are significantly influenced by the nature of the substituents at both carbonyl positio ns of the beta-diketones. Moreover, methyl and chlorine substitution i ncreases by a factor of about 1.1 the thermodynamic isotopic fractiona tion factor relating the -COCHCO- position of the keto form to the hyd roxyl position of the enol.