Dewar pyrimidines

Tetra-r-butylpyridazine (34) is converted into its Dewar isomer (35) when irradiated in pentane with UV light of wavelength > 300 nm. Irradiation of this product at shorter wavelengths, or thermolysis, gives rise to further reaction (91TL57). Irradiation of 4-amino-2,6-dimethylpyrimidine gives the acyclic amino imine via the Dewar pyrimidine as shown in Scheme 2a. The photoisomerization of perfluoropyridazines to pyrazines is considered also to involve Dewar diazine intermediates. 

Kinetically stabilized azetes (271) cycloadd acceptor-substituted nitriles. The initially formed Dewar pyrimidine (272) is subsequently isomerized to the pyrimidine (273) (90SL401). 

Kinetically stabilized azetes 371 cycloadd acceptor-substituted nitriles. The initially formed Dewar pyrimidine 372 is subsequently isomerized to the pyrimidine 373 (Scheme 173) <1990SL401>. Likewise, tetrahydropyrimidines 375 are produced by the reaction of A-tosylazetidines 374 with nitriles under the influence of boron trifluoride or zinc triflate catalysis (Scheme 174) C2005JA16366, 2006TL5393, CHEC-III(8.02.10.1.1)226>. 

The Dewar pyrimidine (207) is an intermediate in the photoconversion of the pyrimidine (208) in acetic acid into the betaine (209). Several examples of the process were recorded.The photochemical ring opening of the pyrimidines (210) in the presence of amines has been reported. ... 

A Dewar pyrimidine had been formerly postulated to be an intermediate in photoisomerization (Eq. 33)," but isolation of a Dewar diazine succeeded much later. 

Kinetically stabilized azetes (575) react with acceptor-substituted nitriles in a [4 -I- 2] cycloaddition step (Scheme 91). The initially formed Dewar pyrimidine (576) is subsequently isomerized to the pyrimidine (577). The sterically demanding substituents necessary for the stabilization of the azetes are thus introduced into the pyrimidine ring <90SL40i>. 

The HPLC-MS/MS assay was also successfully applied to the measurement of UV-induced dimeric pyrimidine photoproducts [123, 124]. The latter lesions were released from DNA as modified dinucleoside monophosphates due to resistance of the intra-dimer phosphodiester group to the exonuclease activity during the hydrolysis step [125, 126]. The hydrolyzed photoproducts exhibit mass spectrometry and chromatographic features that allow simultaneous quantification of the three main classes of photolesions, namely cyclobutane dimers, (6-4) photoproducts, and Dewar valence isomers, for each of the four possible bipyrimidine sequences. It may be added that these analyses are coupled to UV detection of normal nucleosides in order to correct for the amount of DNA in the sample and obtain a precise ratio of oxidized bases or dimeric photoproducts to normal nucleosides. 

Isomerization into an unstable Dewar-like intermediate has been invoked recently to explain the formation of 2-amino-3-cyano-pent-2-en-4-amine (18) as the unique product of the photolysis at 2537 A, of 2,6-dimethyl-4-amino pyrimidine (17).80,81 The quantum... 

The reaction of Dewar pyrimidinone 220 with water in 1 9 mixture of water and acetone at 20°C for 1 hour afforded 4//-pyrido[ 1,2-a]pyrimidin-4-one 108 and enamine 107 in 34% and 64% yields, respectively [89JCS(P1)1231]. Enamine 107 was formed by the cleavage of bond a of 4-hydroxyazetidin-2-one 221, and ring closure of enamine 107 by elimination of water gave 4//-pyrido[l, 2-a]pyrimidin-4-one 108 (Scheme 15). When the solvent polarity was increased, the cleavage of bond b of 4-hydroxyazetidin-2-one 221 also occurred. The reaction in aqueous acetoni-trile-d3 at 35°C for 37 hours gave 4//-pyrido[ 1,2-a]pyrimidin-4-one 109 and lactam 222 in 85% and 10% yields, respectively. The reaction of Dewar... 

The Dewar pyrimidinone 644 (R = /Bu) could be isolated in 16% yield when 2-/m-butyl-6,7,8,9-tetrahydro-4//-pyrido[ 1,2-a]pyrimidin-4-one 643... 

When Dewar pyrimidinone 644 (R = /Bu) was left to stand in acetonitrile containing hydrogen sulfide at 0°C for 15-19 hours, hexahydro-4//-pyrido[2,l-fe][l,3]thiazin-4-one 223 and tetrahydro-4f/-pyrido[ 1,2-a] pyrimidin-4-one 643 (R = /Bu) were obtained in 52% and 32% yields, respectively [89JCS(P1)1231]. When pyrido[2,l-/ ][l,3]thiazine 223 was set aside for 64 hours at 35°C in CDC13, pyrido[ 1,2-a]pyrimidin-4-one 643 (R = /Bu) was obtained in 95% yield. The hydrated enamine 107 in methanol at 16-23°C reverted to the bicyclic pyrido[ 1,2-a]pyrimidin-4-one 643 (R = /Bu) after 2 days in almost quantitative yield [85JOC166, 85TL3247 89JCS(P1)1231]. 

Dewar pyrimidinone 657 was obtained in 92% yield when a solution of pyrido[l, 2-a]pyrimidin-4-one 114 (R = Ph) in acetonitrile was irradiated with a medium-pressure mercury lamp at 20°C (86CC687). 

Clingen, P. H., Arlett, C. F., Roza, L., Mori, T. Nikaido, O., Green, M. H. L. 1995. Induction of cyclobutane pyrimidine imers, pyrimidine(6-4)pyrimidone photoproducts and Dewar valence isomers by natural sunlight in normal human mononuclear cells. Cancer Res. 

Many exeunples of photorearrangement arising by 4tt- and 6ir-electrocyclic pathways have been reported. Full experimental details for the photohydration of the pyrimidin-4-ones (10) to the enamides (11) via the Dewar pyrimidinones (12) have been published. 6fr-Electrocyclizatlon followed by elimination of benzoic acid is observed in the conversion of the 4-aryl-N-... 

Another detailed treatment for pyridine, pyridazine, pyrimidine, pyrazine, 1,2,4,5-tetrazine, and a number of five-membered aromatic heterocycles is based on AMI semiempirical calculations <89H(28)ll35>. Dewar and Holder s values for the aromatic energies are all lower than Wiberg s benzene (28.3 kcal mol ), pyridine (25.6 kcal mol ), pyridazine (22.7 kcal mol ), pyrimidine (25.0 kcal mol ), pyrazine (24.6 kcal mol ), and 1,2,4,5-tetrazine (12.4 kcal mol ) again the tetrazine system seems to be least stabilized. 

Studies on DNA damage include also examples of photoisomerization reactions. As explained in section 5.2.3, UV-irradiated DNA undergoes photocycloaddition processes which result in the formation of different photoproducts. Among the photoadducts, the pyrimidine (6-4) pyrimidone dimer is the most commonly found in experiments. This species can further evolve, generating the Dewar isomer via a photoinduced process. The interconversion mechanism between both photoisomers has been analysed by Ai et alP ... 

Dimerizations between adjacent pyrimidine bases are by far the most prevalent photoreactions resulting from UVC or UV-B irradiation of DNA (Table 140.1), with the relative induction dependent on wavelength, DNA sequence, and protein-DNA interactions. The major photoproducts in DNA are the cydobutyl pyrimidine dimer (CPD), formed through the exdted triplet state, and the pyrimidine-(6-4)pyrunidone dimer [(6-4)PD], formed from a Patemo-Biichi reaction. The (6-4) photoproduct undergoes further UV-B-dependent conversion with its valence photoisomer, the Dewar pyrirnidinone. In addition to the major photoproducts, rare dimers may also form, such as the adenine-thyrnine heterodimer or the 2-imida-zolone(5 )pyrimidone product, another photoisomerization product of the (6—4)PD. 

The Chemistry of Lesion Formation Cyclobutane Pyrimidine Dimers (6- ) Photolesions The Dewar Valence Isomer The Spore Photoproduct Other DNA Photoproducts. 141 2... 

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