1.2.4- Triazole, 3-amino-5-methylthio

Reaction of ethyl 5-amino-3-methylthio-l//-pyrazol-4-carboxylate 267 with sodium nitrite in the presence of hydrochloric acid gives the diazo intermediate 268, which on treatment with active methylenic compounds such as ethyl a-chloroacetate or a-chloroacetylacetone affords the hydrazonyl chlorides 269 and 270, respectively, whose reaction with triethylamine in refluxing ethanol convert them into ethyl 4-hydro-2-methylthiopyrazolo[5,l-c]-[l,2,4]triazole-3,6-dicarboxylate 271 and ethyl 6-acetyl-4-hydro-2-methylthiopyrazolo[5,l-c][l,2,4]triazole-3-carboxy-late 272 (Scheme 23) <2001MI1>. 

Contrasting with the reported formation of fused [l,3,4]thiadiazole rings in the course of the reaction of 3-substituted-4-amino-5-thio-47/-[l,2,4]triazoles 83 with various isothiocyanates (cf. Section 11.07.8.3, Table 3), the reactions with methyl isothiocyanate and with phenylisocyanate afford 3,7-disubstituted-6,7-dihydro-57/-[l,2,4]triazolo[4,3-f] [l,2,4]triazole-6-thiones 110 and -triazole-6-ones 111, respectively (Equation 29) <1986MI607, 1992IJB167>.The same reaction of 4-amino-l-methyl-3,5-bis(methylthio)[l,2,4]triazolium iodide 112 with aryl isothiocyanates yields the mesoionic compounds 113 (Equation 30) <1984TL5427, 1986T2121>. 

Amino-3,5-bis(methylthio)[l,2,4]triazole 114 reacts with aromatic nitriles under basic conditions furnishing the l//-[l,2,4]triazolo[4,3- ][l,2,4]triazoles 115 (Equation 31) <1983S415, 1985BCJ735>. 

Similarly, the reaction of 4-amino-l-mcthyl-3-methylthio-l//-[l,2,4]tnazol-5(4//)-onc 116 furnishes 6-aryl-2-methyl-7//-[l,2,4]triazolo[4,3-/d[l,2,4]triazol-3(2//)-ones 117 (Equation 32) <1985BCJ735> and the 4-amino[l,2,4]triazole-5(4//)-thione 118 furnishes 6-aryl-l,3-dimethyl-l//-[l,2,4]triazolo[4,3-3][l,2,4]triazoles 119 (Equation 33)... 

When 3-amino-5-methylthio- 1,2,4-triazole was reacted with diethyl ethoxymethylenemalonate (EMME) in aqueous ethanol at ambient temperature for two days, an addition product (24) was obtained in 38% yield instead of a condensation product (62JCS2222). 

The reactions of 5-methylthio-3-amino- or 3,5-diamino-l,2,4-triazole and diethyl 1-ethoxyethylidenemalonate in boiling ethanol in the presence of sodium ethylate for 1.5-3.5 hr gave l,2,4-triazolo[l,5-a]pyrimidin-7-ones (1123, R = MeS, NH2, R1 = Me) in 44% and 20% yields, respectively. The reaction of 5-methylthio-3-amino-l, 2,4-triazole (R = MeS) and 2-ethoxyethylidenemalonate in boiling pyridine for 4 hr gave 1,2,4-tria-zolo[l,5-a]pyrimidin-5-one (1122, R = MeS, R1 = Me) in 12% yield (61JCS3046). 

Significant contribution in the studying of the MCRs based on aminoazoles, aldehydes, and Meldrum s acid was made by Lipson and co-authors in their publications [ 114—119]. It was established that in some cases these multicomponent treatments can yield positional isomers. For example, refluxing of 3-amino-l,2,4-triazole with aldehydes and Meldrum s acid gave only triazolopyrimidinones 82 [114] (Scheme 36). On the other hand, MCRs involving 3-amino-5-methylthio-1,2,4-triazoles in boiling DMF yielded solely 5-pyrimidinones 83, while the... 

The 3-alkylthio groups in 1,2,4-thiadiazoles are difficult to replace. Thus, 3-alkylthio-l,2,4-thia-diazoles resist the action of aniline at 100°C, ammonia at 120°C, molten urea and ammonium acetate however, hydrazine attacks 3-methylthio-l,2,4-thiadiazole (142) forming 3-amino-1,2,4-triazole (143) (Equation (21)) <65AHC(5)119>. In contrast to 3-alkylthiogroups, 5-sulfonyl groups in... 

Schiff bases (112) derived from 4-chlorobenzaldehyde and 1-substituted-5-amino-3-methylthio-l,2,4-triazoles (111) underwent cyclization with phe-noxyacetyl chloride or dichloroacetic acid in the presence of phosphoryl chloride and dimethylformamide to give the 7-(4-chlorophenyl)-fram-6,7-dihydro-3-methylthio-6-phenoxy-l-substituted-l,2,4-triazolo[4,3-a]pyrimidin-5-one 113 and l-substituted-6-chloro-7-(4-chlorophenyl)-3-methylthio 1,2,4-triazolo[4,3-a]pyrimidin-5-one 114, respectively (88JHC173) (Scheme 47). 

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). 

Irradiation of 1,2,4-triazine 4-oxides (124) led to the deoxygenated products, and also, when position 5 was unsubstituted, to 1,2,4-triazoles (364) (76LA153). 4-Amino-l,2,4-triazin-5-ones (365) are photochemically deaminated. This has been demonstrated, in particular, with the 6-r-butyl-3-methylthio compound (8) which is used as a herbicide... 

Penta-azaindenes (8-Azapurines). Part VII. Degradation by Acid of the 6-Methylthio-derivatives of 8-Azupurine and Purines to Thiol Esters such as 4-Amino-5-(methylthio)-carbonyI-l,2,3-triazole. 

Cyclizing 4-amino-3-methylthio-l,2,4-triazoles (167) (83S415) or 4-amino-2-methyl-l,2,4-triazolo-3-thiones (169) (85H2613) with aromatic (83S415 85H2613) or heterocyclic nitriles (85H2613) in the presence of potassium /-butoxide afforded the corresponding 1,2,4-triazolo[4,3-h]-... 

Although 9-methyl-6-methylthio-8-azapurine (39) was cleanly converted to 9-methyl-8-azapurin-6-one by refluxing for 3 days with A acetic acid, the reaction quickly took a different course when a stronger acid was used. When 39 was refluxed with N hydrochloric acid for 15 min, 4-amino-3-methyl-5-(methylthio) carbonyl-1,2,3-triazole (41b) was formed in 94% yield. The 7- and 8-methyl isomers, as well as the 9-benzyl analog and 6-methylthio-8-azapurine, all behaved similarly. An intermediate, isolated in 65% yield during hydrolysis at a lower temperature, was identified as 4-amino-3-methyl-1,2,3-triazol-5-yl(methylthio)methyleniminium (cat-... 

Some other characteristic group absorptions will now be summarized. The thiolester group in 4-amino-3-methyl-5-(methylthio)carbonyl-1,2,3-triazole (the 3-Me derivative of 18a) displayed two strong bands of equal intensity 1630 (C=0 stretching) and 900 (C—S stretching) cm". This and related examples are discussed in Refs. 69JCS(C)2379 and 72JCS(P1)461. The... 

A three-component condensation of 3-amino-l, 2,4-triazole (or its 5-Me and 5-methylthio derivatives), 1 and DMF-dimethylacetal afforded 8,9-dihydro[l,2,4]triazolo[l,5-fl]quinazolin-6(7H)-ones (06RCB1224). Condensation of 3,4,5-triamino-l,2,4-triazole with aromatic aldehydes and dimedone afforded partially hydrogenated 9-aryl-[l,2,4]triazolo[5,l-frJquinazolin-8-ones. The structure of 2-amino-6,6-dimethyl-3-(4-nitro-benzylidene)amino-9-(4-nitrophenyl)-5,6,7,9-tetrahydro[l,2,4]triazolo[5,l-fr]-quinazolin-8-one was confirmed by X-ray analysis (05RCB2903). 

Heated without solvent, the 5-amino-l-(l-carboxyalkyl)-3-methylthio-l//[l,2,4]triazoles (259) undergo cyclization to yield 5,6-dihydro-2-methylsulfonyl-4//-imidazo[l,2-Z>][l,2,4]triazol-5-ones (260) (Equation (71)) <85JHC385>. 

The isolable potassium salts (74) (available from the nucleophilic addition of 4-amino-l-methyl-3-methylthio-l -l,2,4-triazole-5(4//)-thiones (73) to aromatic nitriles in the presence of base) upon acidification with hydrochloric acid cyclize to give 7/7-[l,2,4]triazolo[4,3-fc][l,2,4]triazole-3(2//)-thiones (75) (Scheme 5) <85BCJ735>. 

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