1.2.4- Triazolo pyrimidines, conversion

Cyclization of 5-methoxy(nitro)-4-hydrazinopyrimidines (485) with tri-ethyl orthoformate gave the l,2,4-triazolo[4,3-c]pyrimidine intermediate 486, which cannot be isolated due to its conversion to its [1,5-c] isomer 487 by a Dimroth rearrangement. However, the 5-benzyloxypyrimidine derivative, under the same conditions, afforded a mixture of the 8-benzyloxy derivatives of both [4,3-c] and [l,5-c]isomers 486 and 487, respectively (86TL3127 89JHC687 90H277) (Scheme 95). 

Table 12 Conversion of 3//-triazolo[4,5-]pyridines (215).

In many cases, the literature since CHEC-I of those systems in class (i) has been extensive, mainly because most are related to the purine nucleus by the inclusion of a further heteroatom for example azapurine derivatives which have shown pharmaceutical or physiological action. The methods of synthesis, except in a few cases, have not changed since the publication of CHEC-I and thus more emphasis has been placed on the physical properties, reactivity, and reactivity of substituents of compounds within these systems. In contrast, in most cases very little literature is available for systems of class (ii) and synthesis has assumed paramount importance. Only two reviews since the early 1980s are applicable to this chapter the conversion of [l,2,5]oxadiazolo[3,4- f]pyrimidines (9) to pteridines <82MI 713-01) and the chemistry and physical properties of 1,2,3-triazolo[4,5-djpyrimidines (7) <86AHC(39)l 17>. The incidence of publications relating to the use of Structures (1)-(50) in such applications as pharmaceuticals, agrochemicals, and even explosives has increased since the publication of CHEC-I and these are discussed in Section 7.13.10. 

Radiolabelled derivatives of the herbicide florasulam (N-(2,6-difluo-rophenyl)-5-methoxy-8-fluoro(l,2,4)-triazolo-[l,5-c]-pyrimidine-2-sulphon-amide) (VII) were exposed to natural sunlight in a sterile pH 5 buffer water and in a natural lake water collected from 20 to 30 cm below the surface [70]. The photo degradation was much faster in the natural water system, with a half-life of 3.3 days against 73 days in the buffered aqueous medium. Moreover, the photoproducts produced in the distilled and natural waters were found to be different. Direct photolysis led to the cleavage of the N - S bond with formation of the sulphonic acid derivative (Vila) after 10% of conversion (see Scheme 7). 

Brown, D. J., Nagamatsu, T. Isomerizations akin to the Dimroth rearrangement. III. The conversion of simple s-triazolo[4,3-a]pyrimidines into their [1,5-a] isomers. Aust. J. Chem. 1977, 30, 2515-2525. 

These isomers (XLVIII) are formed as side-products during the cycUzation reaction or when the 2,3-dihydro-l,2,4-triazolo[4,3-a]pyri-midine-3-thiones (XLVII) are heated either in water or water-pyridine mixtures. These isomerisations are probably proceeded by the hydrolysis of the (XLVII) first formed. The hydrolysis likely yields either the Schiff s base of 5-amino-2l4-l,2,4-triazoline-3-thione (XLIXa) or 5-amino-zl4-l,2,4-triazoline-3-thione (XLIXb) and the corresponding -dicarbonyl compound. These substances can now cyclize again either on the Nj or the nitrogen atom. This re-cyclization however will occur most readily on the more nucleophile nitrogen atom of the hydrazino function (Nj). Similar conversion reactions are known and have been studied in detail for the non-thioxo substituted l,2,4-triazolo[4,3-a] pyrimidines 3, 317, 318, 319, 383). 

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