Pyrimidinones tautomerism

Since IR spectra are essentially due to vibrational transitions, many substituents with single bonds or isolated double bonds give rise to characteristic absorption bands within a limited frequency range in contrast, the absorption due to conjugated multiple bonds is usually not characteristic and cannot be ascribed to any particular grouping. Thus IR spectra afford reference data for identification of pyrimidines, for the identification of certain attached groups and as an aid in studying qualitatively the tautomerism (if any) of pyrimidinones, pyrimidinethiones and pyrimidinamines in the solid state or in non-protic solvents (see Section 2.13.1.8). 

N-Alkylation is promoted by prior conversion of the pyrimidinones into their respective silyl ethers. Besides selectivity in the alkylation reactions, silylation confers solubility on molecules which otherwise may be difficult to dissolve in nonhydroxylic organic solvents. Selective N-3-alkylation of uracils requires initial protection of N-1. The alkylation of tautomeric thiones invariably proceeds to give an A-alkyl derivative any N-, 0-, or C-alkylation is less rapid and can be avoided. 

This reaction was extended to prepare 7-nitro- and 9-nitro derivatives of pyrido[l,2-a]pyrimidinone 119 (R = N02, R1 = H R = H, R1 = N02) when the appropriate starting material 118 was heated in boiling dichloro-methane in the presence of triethylamine or when it was stirred in aqueous sodium hydroxide at 20°C (92AJC1825) or treated with sodium azide in aqueous tetrahydrofuran (92AJC2037). Semiempirical molecular orbital calculations (AMI) indicated that the 2-hydroxy-4-oxo tautomeric forms 119 are more stable than the alternative 4-hydroxy-2-oxo tautomeric forms. 

Leszczynski et al. have shown interest in comparing experimental (matrix isolation) and calculated (B3LYP) IR data (frequency and intensity) to discuss the tautomerism of benzo-annelated pyridonone, pyrazinone, and pyrimidinone (144-148). These equilibria were well reproduced by theoretical calculations carried out at the QCISD and QCISD(T) levels. The combined experimental and theoretical results reveal links between aromaticity and tautomerism. Moreover, a UV-induced phototautomeric reaction transforming the oxo forms into the hydroxy tautomers was observed for all (except 3-hydroxyisoquinoline) studied compounds [144], The interest of Leszczynski in problems related to tautomerism, aromaticity, and proton transfer is also apparent in a study of (lH-aza-hetero-2-ylidene)-acetaldehyde and 2-azahetero-2-yl-ethanol tautomeric pairs [145],... 

Amines can be formed directly from tautomeric pyrimidinones by heating with an amide of phosphoric or phosphorous acid, but the vigorous reaction conditions limit the application of this method. 

Bis-2-ureido-4[lF/]-pyrimidinones are capable of self-associating into a duplex structure stabilized by eight H-bonding interactions with 70 that are adaptive through a keto—enol tautomerization (Figure... 

The effect of a 5-substituent on the tautomeric equilibrium of 4-pyrimidinones 53 (R1 = Me R2 = H, Me, MeO, COOEt, CONH2, CN R3 = H) was studied using their acidic and basic ionization constants and the results were confirmed by UV spectroscopy (74CPB1239). It was shown that all these compounds exist in aq. solution as an almost equimolar mixture of two oxo forms with the fraction of the hydroxy form not exceeding 4%. 4,6-Dimethyl-2(l//)-pyrimidinone and 6-methyl-4-pyrimidinone exist predominantly in the lactam form in solution (80JST(62)47, 84H(22)2591). 

Pyrimidinones 53 (R1 = Ph, R2 = R3 = H R1 = R2 = H, R3 = Ph) exist in solution as mixtures of hydroxy and 3//-oxo tautomers with the latter predominating. The same tautomeric interconversion was observed in solutions of palladium complexes of these compounds (96MI385). The data on tautomerism of perimidinones 51 (X = O R = H, Me, Et, -Pr) in solution are contradictory suggesting the predominance of either oxo tautomers 51b (94HCA121) or enol tautomers 51a (88MRC191). Only oxo tautomer was observed for 51 (X = O R = Me) in the solid state (94HCA121). 

As with other members of the azine group, the lactam carbonyl or the tautomeric hydroxy functions in the pyridine as well as in the pyrimidine moiety of pyrido[4,3-d]pyrimidinones have been converted to chloro substituents, in pyrido[4.3-rf]pyrimidin-5(6//)-ones by treatment with phosphoryl chloride alone 527,532 in the case of a pyrido[4,3-t/]pyrimidin-4(3//)-one with additional phosphorus pentachloride.508... 

The IR spectra of pyrimidin-2- and 4-ones show strong bands for C=0 and N—H stretching absorption. The N—H stretching band falls in the region 3360-3420 cm which is associated with an azine ortAo-quinoid structure and means that the major tautomeric form of the 4-isomer is as a 4(3//)-pyrimidinone the N—H stretching band for a 4(l//)-pyrimidinone would be expected in the 3415-3445 cm region. 

There are five dihydropyrimidines. The 1,4- and the 1,6-dihydropyrimidines can readily interconvert by tautomerism because of the mobile NH proton. The common metals to effect hydrogenation can be used . Platinum has been the catalyst of choice for the reduction of the 5,6-double bond of uracils, for example, in the addition of deuterium to uracil to produce [5,6- H2]5,6-dihydrouracil. But in the reduction of 2(l/f)-pyrimidinone and its iV-methyl derivative it is the 1,6-dihydro derivatives which are formed. The addition of hydrogen to the 5,6-bond of thymidine and other 5-substituted uridines is stereospecific with rhodium-on-alumina as catalyst. Rhodium-on-charcoal has been useful for hydrogenation of the 5,6-double bond in uracils, uridine, and isocytosine. Raney nickel readily promotes saturation of the 5,6-double bond. Thio derivatives may either be dethiated or taken further to reduced forms by Raney nickel catalysts . 

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