Pyrimidines 4- -pyrimidinones

The pyrimidine nucleobases have the highest quantum yields for photoreactivity, with thymine uracil > cytosine. The purine nucleobases have much lower quantum yields for photochemistry, but can be quite reactive in the presence of oxygen. As can be seen from Figure 9-3, thymine forms primarily cyclobutyl photodimers (ToT) via a [2ir + 2tt cycloaddition, with the cis-syn photodimer most prevalent in DNA. This is the lesion which is found most often in DNA and has been directly-linked to the suntan response in humans [65]. A [2Tr + 2Tr] cycloaddition reaction between the double bond in thymine and the carbonyl or the imino of an adjacent pyrimidine nucleobase can eventually yield the pyrimidine pyrimidinone [6 1]-photoproduct via spontaneous rearrangement of the initially formed oxetane or azetidine. This photoproduct has a much lower quantum yield than the photodimer in both dinucleoside monophosphates and in DNA. Finally, thymine can also form the photohydrate via photocatalytic addition of water across the C5 = C6 bond. 

Uracil has a similar photoreactivity to thymine, but in RNA. Although the rate of photoreaction is similar, the photoproduct partitioning is different. While uracil forms the cyclobutyl photodimer and photohydrate, there is no evidence that it forms the pyrimidine-pyrimidinone [6 1] photoproduct. Also, the major photoproduct in... 

Irradiation of the dithiin (298) brings about rearrangement and forms the thiophene derivative (299). An extrusion of sulfur also takes place and yields the thiophene (300). The rearrangement is proposed to occur via the ring opened dithione (301) and the episulfide (302). Sulfur-sulfur interactions appear to be a vital component in the photochemical reactions of dithiin-1-oxide (303) to give benzaldehyde and the dithiin (304). Thio analogues of (6—4) pyrimidine-pyrimidinone photodimers have been synthesised. ... 

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). 

Preliminary IR spectral studies were said to suggest that pyrimidinones existed as pyrimidinols <50JCS3062) but this conclusion was promptly reversed <52JCS168) on better experimental evidence subsequent comparison with their N- and O-methyl derivatives showed that the pyrimidinones (39a R = H) and (40a R = H) along with their A-methyl derivatives (39a R = Me), (40a R = Me) and (40b R = Me) all exhibited vqo in the range 1600-1700 cm, whereas the methoxypyrimidines (39b R = Me) and (40c R = Me) showed no such absorptions <53JCS33l, 55JCS211). Closer analysis of the spectra for pyrimidin-4-one (40a R= H) showed that the ort/jo-quinonoid form (40a R = H) is the predominant tautomer (see Section 2.13.1.4). 

Pyrimidine-4/6-thiones (and occasionally 2-thiones) can be made by thiation of the corresponding pyrimidinones providing that there are no sensitive groups present. The method is summarized and exemplified in Section 2.13.2.2.7/). 

Pyrimidine, 5-benzyl-4,6-dimethyl-2-phenyl-synthesis, 3, 118 Pyrimidine, 2-benzyl-5-nitro-synthesis, 3, 130 Pyrimidine, benzyloxy-pyrimidinone synthesis from, 3, 133 Pyrimidine, 4,5-bis(alkylamino)-synthesis, 3, 121 Pyrimidine, 2-bromo-aminolysis, 3, 100 H NMR, 3, 62 reactions... 

Pyrimidine-4(3H)-thione, 6-methoxy-5-nitro-reduction, 3, 88 Pyrimidinethiones acidic pK, 3, 60 S-acylation, 3, 95 N-alkylated synthesis, 3, 139 aminolysis, 3, 94 desulfurization, 3, 93 electrophilic reactions, 3, 69 hydrolysis, 3, 94 oxidation, 3, 94, 138 pyrimidinone synthesis from, 3, 133 reactions... 

Pyrimidinones have been extensively investigated because of their importance in the chemistry of natural products. Initially, the infrared spectra of the hydroxypyrimidines were interpreted to favor their existence in the hydroxy form ° however, in 1952 Short and Thomp-goniso reinvestigated these compounds and concluded that pyrimidin-2- and -4-one probably exist in the oxo form. Solid-state infrared spectra were used in this early work which probably accounts for the difficulties encountered in their interpretation. Brown and his asso-... 

Electrophilic substitution at ring nitrogen atoms has been limited to protonation and iV-alkylation of the anion derived from a pyrido-pyrimidinone.i - Thus, the sodium salt of pyrido-[2,3-d]pyrimidine-2,4-(l//,3ir)-dione and dimethylsulfate yield the 1,3-dimethy] derivative (176). 

It was assumed that pyridine derivative 181 yielded pyrido[l,2-c]pyrimidine betaine 182 under catalytic hydrogenation conditions over (5,S)-Et-DuPHoS-Ph catalyst (99TL1211). 6,7-Dehydro derivative 184 of trequinsin (3) was obtained from pyrimidinone 183 by heating in an 1 1 mixture of MeOH and cone. HCl under reflux (97IJC(B)349). 

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