1.2.4- Triazolopyrimidines 1,2,4-triazolo pyrimidines

Triazolopyrimidine, Triazolo[l, 5-a]pyrimidine, Triazolo[l, 5-c]pyrimidine. Sulfonamide, Penoxsulam... 

Tlie chemistry of one of the four possible classes of 1,2,4-triazolopyrim-idiiies, namely l,2,4-triazolo[l,5- ]pyrimidines, was reviewed in 1993 by G. Fischer [93AHC(57)81]. In two previous chapters published in this series we reviewed the chemistry of l,2,4-triazolo[4,3- ]pyrimidines [99AHC(73)131] and their [4,3-c] congeners [99AHC(75)243]. In this chapter we survey the fourth and last class of 1,2,4-triazolopyrimidines. Tlie literature has been inspected to issue number 26, Volume 129(1998) of Chemical Abstracts. 

Tire final chapter in the present volume is the third of a triad of reviews of 1,2,4-triazolopyrimidines, and it covers l,2,4-triazolo[l,5-c]pyrimidines. As with the first and second part of this series (which appeared in Volumes 73 and 75, respectively), it is authored by Professor M. A. E. Shaban and Dr. A. E. A. Morgaan (Alexandria University, Egypt). 

Diacetylcyclopropane reacts with 3-amino-l, 2,4-triazole in acetic acid (either aqueous or glacial) to give triazolopyrimidines 28 <%1ZV1322>, whilst a selection of fiised-ring pyrimidines, for example the l,2,3-triazolo[4,S-prepared using amino hetmoarenecarboxamides and esters <96H(42)691 >. 

It is important to note that besides these synthetic pathways a very important access to [ 1,2,4]triazolo[ 1,5 z] pyrimidine derivatives is the Dimroth rearrangement of [l,2,4]triazolo[4,3-c]pyrimidine compounds. This type of ring transformation is specifically discussed in Section 11.16.5.2 these possibilities are also reviewed in Section 11.16.7. As these isomerizations always take place into the direction of the [l,2,4]triazolo[l,5-c]pyrimidine ring, in several studies only these products are described without special (or any) note of the primarily formed [l,2,4]triazolo[4,3-c]pyrim-idine ring. Table 17 contains the stmctures of some [l,2,4]triazolopyrimidines and benzologues with a fusion site of the triazole ring that have been formed via transformation of the isomeric [ 1,2,4] triazolo[4,3-f]-pyrimidine compounds with or without isolation of these intermediates. 

Table 17 [1,2,4]Triazolopyrimidines and benzologues with a fusion site of the triazole ring that have been formed via transformation of the isomeric [1,2,4]triazolo[4,3-c]pyrimidine compounds...

Fusion of a 1,2,4-triazolo ring onto a pyrimidine nucleus to form 1,2,4-triazolopyrimidine systems may take place in four different modes that lead to the following isomeric structures, all of which possess a nitrogen bridgehead (alternative non-IUPAC nomenclatures are also given) ... 

R1 = R2 = H) gave the triazolo[l,5-a]pyrimidines (125), but with 124 (R1 = R2 = Me) afforded the dioxo derivative 126, and with a-cyano- y-butyrolactones (127) or 2-amino-3-ethoxycarbonyl-5,6-dihydro-4//-thiopyran (129) gave the triazolopyrimidines 128 and 130, respectively (81JHC1287). Treatment of 4-ethoxymethylene-2-phenyl-5(4//)-oxazolone (131) with 5-amino-3-methylthio-l//-1,2,4-triazoles gave the triazolo[l,5-a]pyrimidi-none 132 and the [4,3-a] isomer 133 (93H955) (Scheme 24). 

C-Alkyl-l,2,4-triazolo[4,3-a]pyrimidines are distinguished from their respective [l,5-a]isomers by their UV absorption at longer wavelength. The UV spectra (at pH 2 and pH 10) have been used to differentiate the isomeric 5- and 7-hydroxy-l,2,4-triazolopyrimidines this differentiation may be confirmed by the IR stretching frequency of the CO group. The isomeric A-alkyl-l,2,4-triazolopyrimidines are more readily distinguished by their IR spectra (68T2839). H and 13C NMR and UV spectroscopy have been... 

Refluxing of dihydroazoloazines and a,(3-unsaturated ketones in a methanol solution of sodium methoxide proceeds in a Michael-type addition. For example, reaction of 2-methyl-5,7-diaryl-6,7-dihydropyrazolo[l,5- ]pyrimidine 387 and chalcone 5 under these conditions yields adduct 388 [297] (Scheme 3.102). Treatment of 2-methyl-substututed triazolopyrimidine 389 with ketone 5 leads to cyclization with formation of the triazolo[5,l-Z ]quinazoline moiety [324]. 

ALS herbicides. Two classes of ALS-inhibiting herbicides are the sulfonylurea herbicides, discussed in Sections 2.1.2.1 and 2.2.3.1, and the imidazolinone herbicides. A third class of ALS-inhibiting herbicides is the 1,2,4-triazolo [1,5-a]pyrimidine-2-sulfonanilides. The triazolopyrimidine sulfonanilides act by disrupting the biosynthesis of branched chain amino acids in plants. Representatives of this class of herbicides include florasulam (Boxer , Nikos ) [151], initially introduced in Belgium in 1999 and used for the postemergence control of broadleaf weeds in cereals and corn, and flumetsulam (Broadstrike ) [152], used alone or in combination with other herbicides for the control of broadleaf weeds in soybean and corn. 

The reaction of 2-thiovioluric acid (69) with hydrazine hydrate in boiling ethanol afforded triazolopyrimidine derivative 70, but in boiling acetic acid yielded N-acetyltriazolo[4,5-d]pyrimidine derivative 71. In the same manner, the N-phenyl and A-methyl-l, 2,3-triazolo derivatives 72 and 73 were obtained through the condensation of 69 with phenylhydrazine and with methylhydrazine, respectively (91MI1) (Scheme 13). 

Nucleophilic reagents attack the 7-position of the triazolopyrimidine ring when a leaving group is present. Replacement of the sulfur atom at that position can be achieved after its alkylation. Here, methylation of 3-(3-chlorophenyl)-l,2,3-triazolo[4,5-d]pyrimidine-5,7-dithione (150) af-... 

The amino group at the 5-position on the 3//-l,2,3-triazolo[4,5-d]pyrimi-dine ring was converted into a halogen atom by treatment with isopentyl-nitrite in halomethanes. 5-Halotriazolopyrimidines, unsubstituted at the 7-position, reacted with butyllithium to give 7-butyl-6,7-dihydro-3-phenyl-3//-l,2,3-triazolo[4,5-d]pyrimidines, whereas in the 7-substituted-5-halo-triazolopyrimidines a halogen-metal exchange reaction took place and... 

Replacement of the two chlorine atoms in 3-phenyl-5,7-dichloro-l,2,3-triazolo[4,5-d]pyrimidine gave 3,5,7-trisubstituted triazolopyrimidine derivatives [84JAP(K)5962595], which showed anticarcinogenic activity against sarcoma tumor cells in mice. Compounds 159 have been used as an-ticarcinogenics [81JAP(K)8131586,81JAP(K)8131587]. 

Triazolopyrimidine 313 was synthesized by the diazotization of diamine 312 (95JMC587). The triazolo[4,5-d]pyrimidine 315 was prepared by heating the diazo derivatives 314. The latter were obtained from the reaction of l,3-dimethyluracil-6-arylhydrazones with 2,4-diazido-6-(cyanomethoxy)-l,3,5-triazine (94MC208) (Scheme 63). 

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