4- Hydroxypyrimidine 4-pyrimidone

Repeat your analysis for tautomeric equilibria between 4-hydroxypyridine and 4-pyridone, 2-hydroxypyrimidine and 2-pyrimidone and 4-hydroxypyrimidine and 4-pyrimidone. For each, identify the favored (lower-energy) tautomer, and then use equation (1) to calculate the ratio of tautomers present at equilibrium. Point out any major differences among the four systems and rationalize what you observe. (Hint Compare dipole moments and electrostatic potential maps of the two pyridones and the two pyrimidones. How are these related to molecular stability )... 

Since a knowledge of the correct tautomeric form of the pyrimidines is a requisite for understanding the mode of binding to active sites, as well as nucleic acid structure and modification, the formulae of the conventionally-named 2- and 4-hydroxypyrimidines are presented in the correct lactam, or pyrimidone, form in this chapter. Other physical properties of the pyrimidines, such as dissociation constants, protonation sites, and distribution coefficients, are presented in cases where there is a known relation to drug activity. Biogenesis and enzyme control mechanisms are discussed where they relate to an understanding of inhibitor action. 

The pyrimidone ring system is not fully aromatic, since such compounds exist as amides, rather than hydroxypyrimidines, and the rr-system does not extend fully around the ring. In the case of the uracils, the 5,6-double bond possesses allylic character, and various relatively stable adducts can be obtained, for example, with bromine or chlorine water [210, 486—488]. Catalytic reduction across the 5,6-double bond is also readily accomplished [441, 489—491]. 

Extra nitrogen heteroatoms in the ring provide alternative sites for the tautomeric proton. 4-Hydroxypyrimidine, for instance, can exist as such (92), or in the 1H- (93) or 3H- (94) pyrimidone... 

Hydroxyl groups substituted at positions 2- and 4-(6-) of the pyrimidine nucleus exist mainly in the pyrimidone form [1-4]. The only true hydroxyl position on this ring system is position 5. This hydroxyl group is of phenolic character and all 5-hydroxypyrimidines give a positive (blue-violet coloration) test with ferric chloride. Because of the relative difficulty in synthesis of all but a few compounds, most 5-hydroxypyrimidines have not been extensively studied. 

---