6- Azauracil dioxo derivatives

In agreement with the results of Cattelain, further methylation of the 3-methylmercapto derivative (96) results practically exclusively in 2-methyl-3-methylmercapto-5-oxo-2,5-dihydro-l,2,4-triazine (97). Further methylation of 5-methylmercapto derivative (90) yields 2-methyl-5-methylmercapto-3-oxo-2,3-dihydro-l,2,4-triazine (100). Their structure was confirmed by acid hydrolysis leading to 2-methyl-3,5-dioxo derivatives (62), As was already mentioned, this reaction is a suitable general procedure for preparing the 1-alkyl derivatives of 6-azauracil. ... 

According to the triazine nomenclature, 5-azauracil is 2,4-dioxo-l,2,3,4-tetrahydro-l,3,5-triazine (2). The subject index of Chemical Abstracts prefers s-triazine-2,4(lH,3H)-dione. Furthermore, some authors use a name derived from the lactim structure, 2,4-dihydroxy-s-triazine (3). The numbering of the substituents is the same for all these types of nomenclature. 

In this connection the possibility of oxidation of these substances to the tetrahydro derivatives should be mentioned. It was made use of by Thiele and Bailey for the preparation of 6-methyl-3,5-dioxo-2,3,4,5-tetrahydro-l,2,4-triazine (6-azathymine) (46) and only recently by Grundman et al. for that of 6-azauracil (42). 

The preparation of W-alkyl derivatives of 6-benzyl-3,5-dioxo-l,2,4-triazine by hydrolysis of the corresponding alkylmercapto derivatives was systematically studied by Cattelain. The conversion to known alkyl derivatives of dioxotriazines was used to determine the structure of alkylated methylmercapto derivatives. As will be shown later (e.g., Section H,B,4,b) this procedure has a general preparative significance for 1-alkyl derivatives of 6-azauracil. ... 

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... 

Oxidation of the hexahydro to tetrahydro derivatives was mentioned in connection with the synthesis of 3,5-dioxo-l,2,4-triazines (e.g., Section II,B,2,a). The reverse procedure, hydrogenation of the tetrahydro derivatives, was used with 6-azauracil, 6-azathymine, and their iV-methyl derivatives. With all these compounds hydrogenation proceeds smoothly in the presence of Adams catalyst. Only the hydrogenation of l-methyl-6-azathymine was not successful. ... 

In a preliminary communication, the dihydroxy-1,2,4-triazine derivative 163 has been assigned the structure shown on the basis of infrared evidence. The pK and ultraviolet and infrared spectral data support the formulation of 6-azauracil (164) as a dioxo compound. 

The structures of 5-azacytosine and related compounds are of interest because of their biological importance (see Section 2.20.5.6). l-Methyl-5-azacytosine exists in the amino-oxo form (23). 5-Azauracil (l,3,5-triazine-2,4-dione) is of particular interest. IR spectra indicate that it exists in the dioxo form in the solid, but H NMR studies have been interpreted to show that it exists in the monoenolic form in solution. The spectra showed a non-exchange-able sharp singlet at 8.18 8 (H, 24) (760MR(8)224). Derivatives of 5-azacytosine and 5-azauracil are covalently hydrated. Thus 5-azauridine exists entirely in the crystal form as (25) (76MI22000, p.l39>. 

---

See also in sourсe #XX -- [ ]

See also in sourсe #XX -- [ ]

---