5- Azauracil structure

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. 

Works on the oxidation of uric acid has unequivocally established the triazine structure > ° (9) of oxonic acid. This is further confirmed by the straightforward synthesis described by Piskala and Gut. ° The reaction of biuret (11) with potassium ethyloxalate yielded a potassium salt (24), that with ethyl oxamate, the amide of oxonic acid (25). Both these compounds were converted to 5-azauracil. An analogous reaction with diethyloxalate which should produce an ester of oxonic acid resulted in a mixture of urethane and parabanic acid, however. 

A detailed investigation of the tautomeric structure of 6-azauracil was carried out by Jona and Gut and by Horak and Gut. They measured the UV and IR spectra and compared similar systems and their derivatives in which the lactam or lactim configuration was fixed by A - or 0-substitution (as will be seen later no 0-alkyl deriva-... 

The sodium or potassium salt of 6-azauracil in aqueous ethanol, anhydrous ethanol, or ethylene glycol reacted with methyl iodide practically exclusively to give the 3-methyl derivative (63). In toluene the sodium, potassium, and mercuric salts produced no methylated derivatives whereas the silver salt also yielded the 3-methyl derivative, Similarly, the 3-methyl derivative was prepared from the mercuric salt of 6-azathymine, and its structure was established by hydrolysis to pyruvic acid 4-methylthiosemicarbazone. ... 

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. 

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. ... 

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. ... 

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. 

Some of the older, and cheaper, drugs are still in use despite the problems of resistance and have thus been included in this review of the use of heterocycles in coccidiosis control. Both academic and industrial research in this area continues apace with field trials on arprinocid (68) and reports of activity in new structural classes, e.g. azauracils (69) and acridines (70). Whether these very recent discoveries will have any longer lasting utility than many of their predecessors remains to be seen. 

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>. 

Photoaddition of alkenes to the azathymine (227) affords the adducts (228) the structures of which were determined by -ray crystallography. Acetone-sensitized irradiation of the azauracil derivative (229) yields the cyclobutane (230). Irradiation of the uracil (231) in isotropic solvents is known to yield all four (2-1 2)-dimers in low yield especially at low concentrations. A study has shown that dimerization in smectic media affords a high yield (94X) of the trans-anti dimer (232). In frozen solutions the specificity is reversed and the CIS-anti dimer (233) is formed. The influence of a variety of media on this process was studied in detail. A theoretical treatment of the photochemical addition of alkenes to psoralens such as (234) has been published. ... 

Novel mesoionic structures 22 have been obtained via the internal cyclization of thio- and amino-acid derivatives of 6-azauracil 21. These compounds undergo ring-opening reactions with amines to yield the respective 6-azauracil amides 23. <05TL5325>. 

Contrary to the finding of Dekker and Oort (1964), Matolcsy and Doma (1967) reported contact antifungal action of 6-azauracil, but not of its riboside, 6-azauridine (Matolcsy and Doma, 1969), formed in the initial metabolic step. The activity of 6-azauracil proved to be highly structure-specific, and any alteration in its molecule resulted in a loss in activity. 

The simplest 1,2,4-triazine of which the structure has been determined by x-ray crystallography is still the 5-(4-chlorophenyl)-l,2,4-triazine (8) <74JHC743>. Wilson and Wadsworth, with 1,2,4-triazine-3,5(2//,4Ff)-dione (I) (6-azauracil), have shown that it is possible to solve crystal structures of simple organic molecules from very poor x-ray powder diffraction data. <90AX(A)258>... 

A CNDO/2 method has been applied to calculate structural parameters of 5-azauracil <82ACH35l>. Ab initio and x-ray deformation densities have been compared in cyanuryl chloride the basis sets examined range over STO-3G, 3-21G, 4-31G, 6-31G, and 6-31G. Good agreements were found when a polarization basis set was employed in the calculation of the electronic structure <89JST(202)111>. 

Potter, B.S. Palmer, R.A. Withnall, R. Chowdhry, B.Z. Price, S.L. A/,a analogues of nucleic acid bases Experimental determination and computational prediction of the crystal structure of anhydrous 5-azauracil. J. Mol. Struct. 1999,485 486,349-361. 

Recent studies on the photophysics of the indole,6-azauracil and adenine molecules have been selected here to illustrate both the application of the PRPA computational technique and the differences between photostable and non-photostable molecules. Figure 3 schematizes the energy profiles for the main decay pathways towards the restored ground-state equilibrium structure after the absorption of UV light in the... 

The structure of 6-azauracil is compared with that of uracil [21] in Figure 1. In... 

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