4- Amino-1,2,4-triazol-3 -thiones

Artemov and Shvaika treated a number of 2-aryl-l,3,4-oxadiazoIe-5(4//)-thiones (293) with methylhydrazine (R = Me) and obtained a mixture of 1-methyl-1,4-dihydro-1,2,4,5-tetrazine-6(5//)-thiones (294) and 4-methylamino-l,2,4-triazole-3-thiones (295 R = Me) (71KGS905). A similar reaction was reported by Konig and his coworkers, who treated 5-(4-pyridyl)-l,3,4-oxadiazole-2-thione (293 Ar = py) with hydrazine (R = H) and obtained a compound which was either the l,2,4,5-tetrazine-6-thione (294 R = H) or the 4-amino-1,2,4-triazole-3-thione (295 R = H) (54CB825, 56GEP953801). 

Amino-3-methyl-5-thione-l,2,4-triazole with [HgR(MeCOO)] (R = Me, Ph) gives complexes 186, where coordination occurs via the sulfur and amino nitrogen atoms (93JOM(450)41). In the crystalline state, intermolecular interaction of the mercury site with the endocyclic nitrogen atom of the neighboring unit is also observed. 

Bis(bromomethyl)quinoxaline and 4-amino-1,3,4-triazole-3(27/)-thione gave 2,3-bis(4-amino-l,2,4-triazol-3-ylthiomethyl)quinoxaline (281) (KOH, EtOH, 20°C reflux, 1 h 71% analogs likewise). ... 

Ligands with S donors in addition to N and or O donors bound to Co11 are reasonably large in number. For example, the 4-amino-3-alkyl-l,2,4-triazole-5-thione can bind Co11 as a chelate employing the primary amine and thione substituents on the five-membered ring,510 whereas the trifluoromethyl ligand (afmt) forms [Co(afmt)2(H20)2](N03)2, defined as the A -irons isomer... 

The alkylation of 4-amino-l,2,4-triazolo-3-thione derivatives using haloalkyl nitriles to give the S-alkylated product as a result of alkylation of the 3-mercato-l,2,4-triazole tautomer, or the corresponding N-alkylated product resulting from reaction with the 3-thione tautomer, has been studied extensively optimum conditions have been developed to provide either the S- or the N-alkylated products in good yields <2000PS(167)219, 2003BML2601>. 

In the ring closure of 5-amino-2,3-dihydro-17/-l,2,4-triazolo-3-thione 431 (R = NH2) with 1,2-dibromoethane in the presence of sodium methoxide (2equiv), compound 42 was formed as the main product (Scheme 50) <2003JHC821>. Similarly, the same type of functionalized thiazolo[3,2-A][l,2,4]triazoles 440 and 441 were isolated in the reaction of 1,2-dibromoethane with 2,3-dihydro-17/-l,2,4-triazolo-3-thione (431, R = H) or 2,3-dihydro-5-methyl-l/7-l,2,4-triazolo-3-thione (431, R = Me), using DMF as the solvent in the presence of potassium carbonate and benzyltriethylammonium chloride (CBTEA) (Scheme 50) <2004PS(179)1799>. 

The Schiff base derivatives 73 of the 3-hetaryl-substituted 4-amino-3-thiol-l,2,4-triazoles, on treatment with acetic anhydride, undergo cyclization to give the corresponding 3-substituted-5-acetyl-5,6-dihydro-6-phenyl[l,2,4]triazolo[3,4-7][l,3,4]thiadiazoles 76 (Equation 16) <1990IJB135>. Similar treatment of 4-(A-bcnzoylamino)-4,5-dihydro-l-methyl-3-mcthylthio-1 //-[ 1,2,4 triazolc-5-thione 77 leads to the [l,2,4]triazolo[3,4-4][l,3,4]thiadiazolium trifluoromethanesulfonate 78 (Equation 17) <1986LA1540>. 

The most widely used method for the preparation of [l,2,4]triazolo[3,4-A][l,3,4]thiadiazoles 85 employs 4-amino-5-thio-4/7-[l,2,4]triazoles 83 or 4-amino[l,2,4]-triazole-5(47T)-thiones 84 as starting materials. The reaction of the triazoles 83 or 84 with carbonic acid derivatives furnishes [l,2,4]triazolo[3,4-4][l,3,4]thiadiazoles with a heteroatom substituent (N, O, S) at position 6 the O- and S-functions are formulated as 6-hydroxy and 6-thio derivatives 85a or as thiadiazol-(5/7)6-ones and -thiadiazole-(577)6-thiones 85b, respectively reaction with carboxylic acid derivatives provides the 6-substituted-[l,2,4]triazolo[3,4-4][l,3,4]-thiadiazoles 85c (Equation 20 Table 3). 

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>. 

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)... 

Amino-l,2,4-triazines (86) react with phenylhydrazine to afford 2-phenyl-l,2,3-triazoles (135) (60MI21900). 3-Thioxo-l,2,4-triazin-5-ones (76) are transformed into 1,2,4-triazole-3-thiones (136) by treatment with sodium methoxide (72BSF1511). Treatment of compound (137) with acetic anhydride in the presence of sulfuric acid led to the isolation of the pyrazole (138) (10JA1499). 

The reactions of 7-chloro-pyrimido[5,4-/][l,2,4]triazolo[3,4- ]l,3,4] thiadiazepines 81a-c with different nucleophiles were described in order to obtain new derivatives with possible antitumor activity <2003MI46>. The substituted 81a-c were prepared by cyclocondensation of 4,6-dichloro-2-methylthiopyrimidine-5-carbaldehyde 82 with the corresponding 3-substituted 4-amino-l,2,4-triazole-5-thiones 83. The different reactions as well as the corresponding yields are described in Scheme 8. Interestingly, hydrolysis occurred even during 111 NMR experiments in DMSO at 80 °C. 

The synthesis of a new series of polyfused l,2,4-triazolo[3,4- ][l,3,4]thiadiazepines by reactions of 3-phenyl-5,6,7,8-tetrahydro[l,2,4]triazolo[3,4-A [l,3,4]thiadiazepine-6,8-dione 98 has appeared <2002PS2871 >. The starting material was obtained in good yield via the reaction of 4-amino-5-phenyl-l,2,4-triazole-3-thione 99 with malonyl... 

In a study on reactions of 4-amino-3-( 1,3-di phenyl-l//-pyrazolM-yI)M,5-dihydro-[ 1,2,4]triazole-5( l//)-thionc 206 with different reagents, some novel [l,2,4]triazolo[3,4-/)][l,3,4]thiadiazepines 207-209 were obtained. The starting material 206 was prepared in good yield by the reaction of the oxadiazole thione 210 with hydrazine hydrate <2006ARK(X)137>. Results and reagents are shown in Scheme 31. 

Amino-l,3,4-thiadiazoIium salts (97) on treatment with alkali rearrange to mesoionic l,2,4-triazole-3-thiones (98) probably by deprotonation of (97), nucleophilic attack at C-5, followed by ring cleavage and recyclization to (98) (75SST(3)687, p. 690). ... 

Several papers have dealt with 1,2,4-triazolo[3,4-fc][ 1,3,4]thiadiazines including synthesis of new derivatives and tautomeric studies <02SC3455 02ZN(B)552 02PS487> and a one-pot synthesis starting from 4-amino-5-substituted-l,2,4-triazole-3-thiones involving a solid acid-induced cyclocondensation <02PS2403>. 

G2N3 N N N C c l,3-Dimethyl-4-(l,2,3-triazolyl)sulfide 3-methyl-2-phenyl-l,2,3-triazol-l-ine-4-thione 2-(4-chlorophenyl)-4-amino-5-benzoyl-l,2,3-triazoleaf... 

The reaction of 4-amino-5-hydrazino-l,2,4-triazole-3-thione (38) with aldehydes (740PP156) has found clinical applications but the wide applicability of the reaction limits its specific use. 

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]-... 

Dickinson and Jacobsen [74AC298 75JCS(P1)975] prepared 1,2,4-triazolo[4,3-6]1.2,4,5-tetrazine 520 by reacting 6-phenyl-3-hydrazino-1,2,4,5-tetrazine (519) with carbon disulfide or by reacting 4-amino-5-hydrazino-l,2,4-triazol-3-thione (522) with benzaldehyde in alkaline medium. The reaction involved the air oxidation of tetrahydrotriazolo-... 

Amino-5 hydrazino 3-merc[Pg.216]

Azapurine and 1,1-dimethylhydrazine, in water, (room temp, 18 h) furnished 4-dimethylhydrazonomethylenamino-1,2,3-triazole-5-carbalde-hyde dimethylhydrazone (47a). 8-Azapurin-2-one and -2-thione similariy gave the 4-ureido (48a) an(J 4-thioureido (48b) analogs (yields, 63 and 77 %, respectively). 2-Amino-8-azapurine did not react with this reagent, but with hydrazine it produced a 90% yield of 4-hydrazonomethylenamino-1,2,3-triazole-5-carbaldehyde hydrazone (47b). On the other hand, 8-azapurine and its 2-oxo and 2-thioxo derivatives underwent a 2 1 reaction with hydrazine (under the same conditions) to give the azines 49a, b, c, respectively, in 72-88% yields. ... 

Two related syntheses of this period must be noted. The malonamide derivative 63, when heated with ammoniacal cupric sulfate (1(X) C, 3 h), yielded 95% of 4-amino-2-phenyl-l,2,3-triazole-5-carboxamide, which was converted to 8-phenyl-8-azapurin-6-one in 67% yield by refluxing with triethyl orthoformate and acetic anhydride (4 h). Alternatively, the triazole amide was changed to the thioamide with phosphorus pentasulfide (79% conversion). This thioamide produced 8-phenyl-8-azapurine-6-thione when... 

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