4- Amino-2-oxopyrimidine

Since 4-aminopyrimidine is known to exist predominantly in the amino form, with a double bond between N(3) and C(4), it bears some structural resemblance to adenine, which may be considered a formal analogue of a 5,6-disubstituted 4-aminopyrimidine, and (at least to some extent) of cytosine, which is 4-amino-2-oxopyrimidine (Table II). This pointed to the possible utility of a detailed examination of the electrochemical behaviour of 4-aminopyrimidine, and some of its methylated analogues. 

The enamino nitriles 299, 300, and 302 react smoothly with various isocyanates to afford heterocondensed 4-amino-2-oxopyrimidines (306).172... 

The equilibrium between the amino and imino forms of cytosine has also been studied by Cieplak et al.9 Their results agree with those of Colominas et al. In this study, the related 2-oxopyridine and 2-oxopyrimidine molecules were also treated. In both these molecules the amine group of cytosine is not present, and in oxopyridine only one ring nitrogen is present. This enabled the keto-imino tautomerism to be studied in isolation. In both cases the imino form dominates in the gas phase, but the keto form is stabilised by solvation, and dominates in solution, in agreement with experiment. 

A great number of 4-oxopyrimidines have been prepared by cyclization of )8-amino acid derivatives with oxo reagents. All the compounds discussed here involve cyclohexane ring fusion, and therefore the quinazolinone nomenclature can be used. 

A hydrazine or substituted hydrazine in lieu of the amino group on the pyrimidine precursor is also an effective species. In what may be described as a Fischer indole-type reaction, 2-amino-6-hydrazino-4(3//)-oxopyrimidine 129 undergoes thermolytic cyclization when heated with compounds 130 (Scheme 12). The resultant product 131 is obtained in modest yield <1996H(43)323, B-2002MI439>. 

The hydrazone of a 5-formylpyrimidine (114) when treated with sodium hydride and then heated to 150°C also results in formation of a pyrrolopyrimidine (115) (Equation (36)) <89H(29)1993>. In a related reaction, treatment of 2,4-diamino-6(l//)-oxopyrimidine (116) with methyl chloro-formylacetate gives both the pyrrolopyrimidine (117), and the furopyrimidine (118) (Equation (37)) <89JCS(Pl)2375>. The latter can be converted into pyrrolopyrimidine products. Pyrrolopyrimidines with 5-amino substituents can be prepared from 5-cyanopyrimidines utilizing similar chemistry <88LA633>. 

Using similar chemistry l,3-diaryl-2-thiobarbituric acid is acylated with chloroacetyl chloride in the presence of triethylamine. Subsequent (9-alkylation under the mildly basic conditions of sodium acetate yields the 5-oxo derivative <91H(32)907>. It is not necessary to use barbituric acid derivatives to accomplish synthesis of furopyrimidines. Other 6-oxopyrimidines serve well in developing analogues. For example, in a reaction similar to that described above, the acylated pyrimidine (215) undergoes cyclization to a 4-(substituted)amino compound (216) (Equation (74)) <92MI 707-03). 

From ethyl 2-cyanoacetate. 5-Aminopyrazol-3-ones can be conveniently prepared from /7-keto esters with hydrazines. Thus, heating ethyl 2-cyanoacetate 142 with (4-ferf-butylphenyl)hydrazine 143 in ethanolic sodium ethoxide afforded 5-amino-2-(4-ferf-butylphenyl)-2,4-dihydropyrazol-3-one 144 (01JMC3730) (Scheme 33). The reaction that takes place under acidic conditions, between ethyl 2-cyanoacetate 142 and 2-hydrazino-6-oxopyrimidine-5-carbonitrile 145 in boiling acetic... 

Pyrimidine-fused Systems. - Owing to their pharmaceutical interest, many new thienopyrimidine derivatives are still being synthesized. The reaction of 2-amino-3-cyanothiophens with carbonyl sulphide has been used for the preparation of thieno[2,3-c/j-2-thio-oxopyrimidine. The reaction of 2,5-diamino-3,4-diethoxycarbonylthiophen with phenyl isocyanate in the presence... 

Fig. 27 iR spectra of AOP. (a) spectrum measured at 10 K for the compound in a xenon matrix (b) difference spectrum between the spectra measured before and after UV irradiation X > 270 nm) for 60 min (c) scaled harmonic vibrational spectral patterns of keto (lower side) and enol (upper side) forms of AOP obtained at the B3LYP/6-31-F-FG(d,p) level. Reprinted from K. Ohyama, K. Goto, T. Shinmyozu, N. Yamamoto, S. lizumi, M. Miyagawa, M, Nakata and H. Sekiya, infrared spectroscopic studies on 4-amino-6-oxopyrimidine in a low-temperature Xe matrix and crystalline polymorphs composed of double hydrogen-bonded ribbons, Chem. Phys. Lett., 2014, 595,138-143. Copyright (2014), with permission from Elsevier. 

C0H7N3O2, Cytosine monohydrate, 28, 503 39B, 289 42B, 307 C0H7N3O2S, 6-Amino-2-thiouracil monohydrate, 44B, 380 CHH7N3O4, trans-1-Carbamoyl-imidazolidine-4,5-diol, 39B, 291 C4H,4N2Na20sS, Disodium 4-oxopyrimidine-2-sulfinate hexahydrate, 34B, 224... 

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