2- pyrimidine irradiation

Oxidopyridazinium betaines isomerize photochemically into pyrimidin-4(3H)-ones (33). Irradiation of 3-oxidopyridazinium betaine or 1-oxidophthalazinium betaine in water affords similarly the corresponding pyridazin-3(2H)-one (35) and phthalazin-l(2H)-one derivative (37). However, photolysis in acetonitrile affords stable diaziridines (34) and (36) which can be converted in the presence of water to the final products (35) and (37) (Scheme 12) (79JCS(P1)1199). 

There is a scattered body of data in the literature on ordinary photochemical reactions in the pyrimidine and quinazoline series in most cases the mechanisms are unclear. For example, UV irradiation of 4-aminopyrimidine-5-carbonitrile (109 R=H) in methanolic hydrogen chloride gives the 2,6-dimethyl derivative (109 R = Me) in good yield the 5-aminomethyl analogue is made similarly (68T5861). Another random example is the irradiation of 4,6-diphenylpyrimidine 1-oxide in methanol to give 2-methoxy-4,6-diphenyl-pyrimidine, probably by addition of methanol to an intermediate oxaziridine (110) followed by dehydration (76JCS(P1)1202). 

As mentioned above (Section 2.13.2.1.3), bipyrimidine photoproducts can arise, probably by reaction between two radicals. Thus, irradiation of an aqueous solution of 5-bromouracil (ill R=Br) in the absence of oxygen produces a variety of products including uracil, barbituric acid, 5-carboxyuracil (111 R = CO2H), several non-pyrimidine compounds and, as a stable end-product, the biuracil (114 R = H). A similar product (114 R = Me) is formed from 5-bromo-l,3-dimethyluracil (ilS). When two such related uracil derivatives are irradiated together, a mixed bipyrimidine product is formed, inter alia (B-76MI21302). 

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

Azacyclobutane dimers 28 were obtained (84H67, 84H1363) in high yields by irradiation of some pyrimidine 6-azapyrimidine dinucleotide analogs 27. They are unstable in aqueous solution and decomposed back to 27 (Scheme 8). 

A similar strategy has been used to prepare pyrimidines, as well as pyra-zoles and isoxazoles by reacting the enamine intermediate with a variety of bidentate nucleophiles [78]. Microwave irradiation of a cyclic 1,3-diketone 49 and acetal 45 in water generated the corresponding enaminoketone 50 in situ which reacted with amidines, substituted hydrazines or hydroxylamine in only 2 min in a one-pot process to give 4-acylpyrimidines, pyrazoles or isoxazoles, respectively (Scheme 20). 

The one-pot MCR of methylene active nitriles 47 has been used in the synthesis of both pyrano- and pyrido[2,3-d]pyrimidine-2,4-diones in a single-mode microwave reactor [90]. Microwave irradiation of either barbituric acids 61 or 6-amino- or 6-(hydroxyamino)uracils 62 with triethyl-orthoformate and nitriles 47 (Z = CN, C02Et) with acetic anhydride at 75 °C for 2-8 min gave pyrano- and pyrido[2,3-d]pyrimidines in excellent yield and also provided a direct route to pyrido[2,3-d]pyrimidine N-oxides (Scheme 27). 

Bromo-4-chloro-lH-pyrazolo[3,4-d]pyrimidine could be easily fimc-tionalized at C-3 and C-4 in a one-pot two-step microwave-assisted process (Scheme 34) [55]. Ding and Schultz reported that nucleophilic substitution of the addition-elimination type at the C-4 position with amines and anilines smoothly occurred under acidic conditions in dioxane upon irradiation... 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

Zhang RB, Eriksson LA (2006) A triplet mechanism for the formation of cyclobutane pyrimidine dimers in UV-irradiated DNA. J Phys Chem B 110 7556-7562... 

Scheme 5 a Flavin-H-phosphonate and formacetal-linked thymine dimer phospho-ramidite used for the synthesis of the flavin and dimer containing DNA-strands 7-12. b Representation of a reduced flavin- and formacetal-linked cyclobutane pyrimidine dimer containing DNA strand, which upon irradiation (hv) and electron transfer (ET) performs a cycloreversion (CR) of the dimer unit, c Depiction of the investigated oligonucleotides... 

In 1949 Sinsheimer and Hastings<64) reported the almost complete loss of the 260-nm absorption of the pyrimidines upon irradiation in aqueous solution. This effect is now known to be caused by the photochemical addition of water across the 5,6 double bond, as shown below for cytosine ... 

Thienopyrrolopyrimidines can be prepared by a photochemical reaction. Upon heating or irradiation of 4-azido-5-(2-thienyl)pyrimidine in trifluoroacetic acid solution, the tricyclic product is formed in good yield <1989CPB2933> (Equation 1). 

Other variants of this type of ring system are obtained by simple (S -type ) cyclization of the (3-hydroxypropyl-amino)thieno[2,3- /]pyrimidines 475 (Equation 202) <2000PS( 165)221 > and reaction of the parent aminopyrimidine with the enol ether 476 under microwave irradiation (Equation 203) <1999H(51)1819>. 

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