KETO-ENOL-TAUTOMERISM OF PHENACYLPYRAZINE - ACID CATALYSIS WITH PROTONATION AT NITROGEN

Kinetic and equilibrium measurements for ionisation and enolisation of 2-phenacylpyrazine in aqueous solution at 25 degrees C yield a tautom eric constant pK(E) = 2.05 (where K-E = [enol]/[ketone]) and pK(a)s fo r loss of a methylene proton and for protonation at nitrogen of 11.90 and 0.40, respectively. In contrast to 2-phenacylpyridine the low basi city of the pyrazine nitrogens renders an enaminone tautomer less stab le than the enol and a value of pK(M) = 4.4 (K-M = [enaminone]/[ketone ]) is estimated for this equilibrium. Evidence is presented that acid catalysis of keto-enol tautomerism occurs with protonation at the N-1 nitrogen atom rather than carbonyl group (or N-4 nitrogen) despite the proton being bound to oxygen in the enolic product. This,preference r eflects relative magnitudes of binding constants (1/K-a) and activatin g factors (PAF) for protonation at the different positions. Bronsted a nd Marcus equations are used to express catalytic efficiency in terms of equilibrium constants for binding the catalyst to the reactant and products of the uncatalysed reaction. The form of catalysis observed, which reflects the influence of proton binding on the activation energ y of the reaction, is contrasted with that in intramolecular or enzyma tic reactions, which normally derives from approximation of the reacta nts and isentropic in origin. The significance of optimum binding of t he catalyst to the transition state in the two cases is briefly compar ed.