Tautomerism of barbituric acids

Pulse radiolysis studies using optical detection suggested the main species in equilibrium to be the ot-aminoalkyl radical (31) and the A -protonated ot-aminoalkyl radical (32) whereas results from ESR studies were indicative of protonation at the a-carbon site to form the iV-centered radical cation (30). A subsequent study showed that these results could be attributed to kinetic and thermodynamic factors [84]. Thus iV-protonation resulting in the formation of 32 is kinetically favored and is hence observed in the short time-scales involved in pulse-radiolysis systems. In the longer times involved in ESR measurements the thermodynamically more stable N-centered radical cation will be observed. The pA a of 30 and 32 were estimated as 8.0 and 3.6 by use of pulse radiolysis [84]. Using the equation for similar keto enol tautomerism of barbituric acid [97], the ratio of 30/32 was estimated to be 10 /10 = 10", indicating the N-centered radical (30) to be the predominant protonated species. 

The tautomerism of barbituric acid and its derivatives has been briefly discussed in a review on this class of compounds (85AHC(38)229). Eleven tautomers are possible for unsubstituted barbituric acid 162. The position of the tautomeric equilibrium 162a 162b for unsubstituted barbituric acid and its N- and 5-substituted deriv-... 

Two important papers by Gobetto et al. belong to this section. In the first one, the tautomerism of barbituric acid (33) was discussed (08CGD1454). In the solid state, the barbituric acid is well known to exist as two anhydrous forms (polymorph I and II, which differ in the HB network) and a dihydrate phase. They all display the trioxo structure 33a of Figure 7 shown by X-ray diffraction studies. In solution, on the contrary, the barbituric acid may exist as 11 possible structures (Figure 7) because of tautomeric equilibria. 

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