6- Azauracil dissociation constants

A determination of the dissociation constants of the compounds reveals that 5-azauracil (pi a = 6.73) is practically of the same acidity as 6-azauracil and considerably more acidic than uracil, A fundamental difference between 5-azauracil, on the one hand, and 6-azauracil and uracil, on the other, lies in the low stability of 5-azauracil toward acid and especially to alkaline hydrolysis. This fact appears to be in agreement with the differences in electron densities of these substances computed by the simple MO-LCAO method. ... 

The course of alkylations of 6-azauracil is in good agreement with the results of determination of the dissociation constants of 6-azauracil and of its two monomethyl derivatives. On the assumption that a methyl group does not much affect the dissociation constant, and on the basis of the lactam structure, it may be concluded from the values of the dissociation constants iKa of 6-azauracil = 7.00, of l-methyl-6-azauracil = 6.99, and of 3-methyl-6-azauracil = 9.52) that dissociation takes first place at the NH group in position 3. The same results are obtained independently by comparing the pH dependence of the XJV spectra of these compounds. These results represent an exact confirmation of the older observation by Cattelain that the monoalkyl derivatives of 6-substituted dioxotriazines possess different acidity. 

It should be mentioned that a similar comparison of the dissociation constant values of uracil monoalkyl derivatives does not permit the determination of the sequence of dissociation on account of the small differences between the pEo values. However, the pH dependence of the XJV spectra showed that the first dissociation of uracil occurs at the NH group in position 1 and thus differently than in 6-azauracil. This, together with different acidity, represents the main differences between the properties of uracil and its 6-aza analogs. 

By comparing the dissociation constant of 6-azauracil and 6-aza-uridine with those or uracil and uridine, 6-azauridine is now considered to be 1-ribofuranosyl derivative (2-ribofuranosyl-3,5-dioxo-2,3,4,5-tetrahydro-l,2,4-triazine), The same was shown more exactly by comparing the UV and IR spectra and the dissociation constants of 6-azauridine with the two monomethyl derivatives of 6-aza-uracil," Enzymatic synthesis thus, proceeds, in the same way in natural bases and in their aza analogs. 

It was found already by Cattelain that the 3-thioxo derivatives behave as monobasic acids that can be titrated on phenolphthalein and he considered them as more acid than the analogous 3,5-dioxo-triazines. This assumption was recently confirmed by determining the dissociation constants. Just as with 6-azauracil, it was possible to demonstrate, by comparing the dissociation constants of the V-methyl derivatives of all the thioxo analogs, that with the 3-thioxo compounds too, dissociation proceeds first at the NH group in position 3 122... 

A determination of ihe dissociation constants of the compounds reveals that 5-azauracil (pifa = 6.73) is practically of the same acidity as 6-azauracil and considerably more acidic than uracil. 

---