1 -Methyl-1,2,3-triazolo pyrimidines

SEE has so far been the technique most frequently used to validate DPSE methods such as those for the extraction of dioxins from high- and low-carbon fly ash [48], triazolo-pyrimidine sulphonanilide herbicides, trichloropyridinol and PCBs from soil [150,152, 168], and carotenoids and tocopherol from spice red pepper [177]. As noted earlier, neither technique can be said to be better than the other it depends on the characteristics of the analytes to be extracted (e.g. on their polarity and high-temperature stability). Thus, in the extraction of cloransulam-methyl from soil, while the use of subcritical water provided higher recoveries than SEE, the analyte was not hydrolytically stable above 150°C, which entailed using a lower temperature and hence an increased extraction time [152]. In the extraction of PAHs from bituminous coal fly ash [180], extraction with supercritical CO, yielded better recoveries than DPHSE using toluene and methylene... 

Hydrolytic fragmentation of the C5-N6 part took place upon heating 7-methyl-5-propyl-2-thioxo-l,2,4-triazolo[l,5-c]pyrimidine (129) with hydrochloric acid. 3-Acetonyl-5-mercapto-l,2,4-triazole (130) and butanoic acid were obtained as a result of N4-C5, C5-N6, and N6-C7 bond cleavages (65JCS3369) (Scheme 50). 

Wolt ID, ID Schwake, FR Batzer, SM Brown, LH McKendry, JR Miller, GA Roth, MA Stanga, D Portwood, DL Holbrook (1992) Anaerobic aquatic degradation of flumetsulam [N-(2,6-difluorophenyl)-5-methyl [l,2,4]triazolo[l,5a]pyrimidine-2-sulfonamide]. J Agric Food Chem 40 2302-2308. 

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

In a similar tandem reaction, ethyl 2-azido-l-methyl-l/7-indole3-carboxylate 364 is converted to indolo[3,2- ]l,2,3-triazolo[l,5- ]pyrimidin-5-ones 366 via triazole intermediates 365 that are not separated (Scheme 58). Products 366 are obtained in 80-90% yield as potential intercalates of DNA <2003H(60)2669>. 

The glutamic moiety of TNP-351, a pyrrolo[2,3-d]pyrimidine glutamic acid derivative, and related compounds have been transformed into their A-co-masked ornithine analogs which show remarkable antifolate activity <00CPB1270>. The reaction of the heterocyclic enamine 77 with tosyl azide leads to the tosylimino derivative of 1,2,4-triazolo[l, 5-a]pyrimidine 79. Extrusion of nitrogen from the primary adduct 78 is followed by a 1,2-shift of a methyl group to yield 79 <00JHC195>. 

Kleinpeter et al. carried out ab initio and semi-empirical (PM3) calculation in order to rationalize the tautomeric equilibria of 7-hydroxy-5-methyl[l,2,4]triazolo[l,5- ]pyrimidine <1995JST(335)273, 1997JST(435)65>. This compound can exist in four tautomeric forms a-d (Figure 1). The authors concluded that the high computational level available can sufficiently reproduce the position of tautomeric equilibria in solution and, thus, can serve as a useful tool instead of time-consuming experimental studies. 

Figure 1 Tautomeric forms of 7-hydroxy-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine.

Ring opening of also a fused [l,2,4]triazole system by secondary amines has been reported. Chupakhin et al. described that 5-methyl-6-nitro[l,2,4]triazolo[l,5-r ]pyrimidin-7(8/f)one 122 underwent ring opening when treated with various secondary amines to yield pyrimidyl ureas 123 in medium to good yield <2001IZV655>, as shown in Scheme 14. 

In the reaction of 4-benzyl-3-amino-1,2,4-triazole and 1-ethoxyethyli-denemalonate under the previous circumstances, 7-methyl-l,2,4-triazolo[l, 5-a]pyrimidin-7-one (1127) was prepared in 10% yield [67JCS(C)503]. 

An example of synthesis A is that of 5-methyl-1,2,4-triazolo[l,5-a] pyrimidin-7-on (MOT) (3) by Bulow and Haas (09CB4638) given in Scheme 1. This reaction is a pyrimidine synthesis The C3-synthon condenses with a N—C—N moiety, which is a part of an AT. Apparently the reaction passes through the nonisolable intermediate 2 (Section II,A,2). 

Methyl-1,2,4-triazolo[l,5-a]pyrimidin-7-on forms salts with primary and secondary aliphatic amines (61JOC3834). Rather soluble tetrabutylam-monium salts may be convenient for synthesis (91JHC721). Products of synthesis A, formed from 2 mol of AT and 1 mol of acetoacetic ester,... 

Methyl-1,2,4-triazolo[ 1,5-a]pyrimidin-7-on is amphoteric and can be titrated with perchloric acid in glacial acetic acid (61JOC3834). Some derivatives form isolable hydrohalides (75PHA134). Glier et al. (72T5789) formulated a cationic structure at pH 1 from the UV spectrum contrary to that of Hill et al. (61JOC3834). 

A number of mesoionic l,2,4-triazolo[4,3-a]pyrimidines (15) were obtained upon desulfurization of l-methyl-l-(4,6-dimethylpyrimidin-2-yl)thiosemicarbazides (13) with dicyclohexylcarbodiimide (DCC) [88JCS(CC)506 93JCS(P1)705] or by cyclization of l-alkyl-l-(4,6-dimethylpyrimidin-2-yl)hydrazines (14) with carbon disulfide or phosgene [88JCS(P1)351] (Scheme 8). 

A number of 3-(alditol-l-yl)-5-methyl-7-oxo-l,2,4-triazolo[4,3-a]pyrim-idines l,2,4-triazolo[4,3-a]pyrimidines acyclo C-nucleosides (30) were synthesized (95PHA784) by oxidative cyclization of the corresponding aldehydo-sugar pyrimidin-2-ylhydrazones 27 with bromine in water. The alternative structure 29 was eliminated based on finding that acetylation of 30 afforded the same acetylated acyclo C-nucleosides 31 as those obtained by oxidative cyclization of the (A3-acetyl-poly-0-acetyl)hydrazones 28. Compounds 31 were also obtained by one-pot oxidative cyclization and acetylation of 27. In contrast to the oxidation and concurrent bromination of 19 to 25, it was possible to avoid nuclear bromination of 27 and 28 by performing the reaction in the absence of light (Scheme 13). 

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