1.2.4- Triazoles 5-mercapto— from

Synthesis of 5-Mercapto-l,2,3-Triazole Derivatives from 5-Amino-l,2,3-Thiadiazoles... 

From 4-phenylthiosemicarbazide Freund and HempeH obtained a product to which they assigned the structure of a tetrazolinethione. When heated in alkaline solution it was isomerized to a compound which, on the basis of adequate chemical evidence, was considered to be 5-mercapto-l-phenyltetrazole. According to Lieber and Ramach-andran, however, the initial product is 5-phenylamino-l,2,3,4-thia-triazole. Lieber and Slutkin have also converted some di(thiosemi-... 

The thiol group was displaced from 3-mercapto-l,2,4-triazoles 59 using oxidation to yield the corresponding 3-unsubstituted compounds 60a-d in good yield (Equation 19) (Table 5) <2006S156>. 

Mercapto-l,2,4-triazole 67 reacted in a standard coulometric cell with the ortho-quinone generated electroche-mically from 1,2-dihydroxybenzene to give 4-(l//-l,2,4-triazole-3-ylsulfanyl)-l,2-benzenediol 68 via a Michael addition (Equation 23) <2005MI68>. 

Fused heterocyclic systems derived from 3-mercapto-l,2,4-triazole can be obtained by heterocyclization of 4-allyl-l,2,4-triazole-3-thione derivatives by treatment with halogens or mineral acids <1996T791>. Compounds 342 react with bromine yielding thiazolium halides 28 in good yield (Equation 64) <2000RJOC1033>. 

Liu et al. elaborated an efficient synthetic route to [l,2,4][5,l-A][l,3,5]thiadiazine-7-ones 122 <2000M953, 2000JFC111> starting from 3-mercapto[l,2,4]triazoles 121. These compounds were treated with N-substituted A-chloromethylcarbamoyl choride in dimethylformamide (DMF) solution at room temperature for 1-2 h to give the ring-closed products in high yield (>80%) (Scheme 22). 

Several ring-closure reactions for [l,2,4]triazolo[3,4- ][l,3,4]thiadizines have been described, and all these procedures started from 3-mercapto-4-amino[l,2,4]triazole 135 (Scheme 26). A common structural feature of the reagents is the presence of the CH2X (X = halogen atom) moiety which allows the alkylation at the sulfur atom followed by a ring-closure reaction via an elimination step. Some typical ring closures are shown in Scheme 26. 

Qualitative spot tests for aldehydes, in the presence of ketones, are generally only reliable for water-soluble compounds. This problem can be overcome by the use of 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald , Aldrich Chemical Company) in the presence of Aliquat (Scheme 5.27). Under aerial oxidation, the initially formed colourless cyclic adduct changes colour through red to purple. The colourless cyclic aminal can also be formed by ketones, but only the adducts derived from the aldehydes are oxidized to the purple bicyclic aromatic system [28]. Weakly electrophilic aldehydes, e.g., 4-methoxybenzaldehyde, reacts slowly, but will give the positive coloration upon gentle heating to ca. 70°C for one or two minutes. 

Coumarinyl-substituted thiazolo[3,2-h][l,2,4]triazoles have also been reported. They are available in one step by reaction of 5-aryl-3-mercapto[l,2, 4]triazoles with 3-bromoacetylcoumarin (ethanol, reflux, 8 h yield 44-65%) (81AP435) or in a two-step reaction from the corresponding S-alkylated intermediates with PPA [93MI2 94IJC(B)579]. 2-Aminothiazolo[3,2-h][l,2,4]triazoles are also available from 3-mercaptotriazoles. Treatment of 5-amino-3-mercaptotriazole with chloroacetone (DMF, K2CO3) and subsequent acid-catalyzed cyclization yields 146 [90JAP(K)02/142797]. 

V-Amino-3-mercapto-1,2,4-triazoles (240) add DMAD to give adducts 241 derived from initial attack by sulfur.168... 

When benzylbromide is allowed to react with 4-(3-mercapto-5-phenyl-[l,2,4]triazol-4-ylmethyl)-benzamide (32) in order to synthesize the corresponding thiobenzyl adduct 4-(3-benzylsulfanyl-5-phenyl-[l,2,4]tria-zol-4-ylmethyl)-benzamide (33), a nucleophilic sulfur-based resin (34) is employed to trap excess benzylbromide from the reaction mixture affording a final clean product (33).28 In addition, a basic Amberlite (OH-) is added to assist in the efficient deprotonation of the mercapto functionality in (34) as depicted in Fig. 13. 

Amino-5-mercapto-l,2,4-triazole [16691-43-3] M. 116.1, m 298 , pKeskd 3.0, pKEst(2) Recrystd from H2O and dried in vacuo. The acetyl derivative has m 325° (dec) after recrystn from H2O. [Beilstein 26, 3rd/4th SuppI p. 1351.] Also recrystd from EtOH/H20 (3 1, Ig in 50 mL, 50% recovery), m 300-302° dec subject to heating rate (Xmax 263nm, log e 4.12), and S-Benzyl derivative when crystd from CgHg/EtOH (20 1), or CHClj/EtaO has m 109-111° [Godfrey and Kruzer J Chem Soc 3437 7960]. 

The synthesis of [3,4-r]-annulated compounds started from 6-hydrazinopurine derivatives 273. The first method involved reaction with aliphatic or aromatic ortho esters closing the third triazole ring and giving 274 (R = Aik, Aryl). Use of carbon disulfide instead of the ortho esters produced the 3-mercapto-tricyclic 274 (R = SH). 

Thiazolo[2,3-c thiazoles [C2N3-C3NS]. The reaction of 3-mercapto-5-(3-pyridyl)- ,2,4-triazole with 4-BrC6H4COCH2Br gave the sulphide this cyclizes with PPA to give (120), and not (121). 2,3-Dihydro-derivatives of the latter ring system may be obtained from the reaction between acyl-hydrazines and C1(CH2)2NCS in the presence of EtaN. ... 

Aryl-2-(carboxymethyl)(or carboxyethyl)thiazolo[3, 4 2,3]-l,2,4-triazolo[5,4-3]-l,3,3-thiadiazines 234 are obtained from 2-aryl-3-thioureido-4-thiazolidinones 235, which are formed by the addition-condensation of aldehyde thiosemi-carbazones 237 and mercaptoacetic acid. Compounds 235 undergo chemoselective intramolecular heterocyclizations to 5-aryl-2-mercapto-l,5-dihydrothiazolo[3,4- ]-l,2,4-triazoles 236, which in turn undergo condensation with a-amino acids to yield 1,3,5-thiadiazines 234 (Scheme 44) <1994JFA811>. 

Sodium hydroxide 5-Mercapto-l,2,3-triazoles from 5-amino-l,2,3-thiadiazoles... 

IR data for Co(II), Ni(II) and Cu(II) complexes of pyridine-2-(17f)-thione-3-cyano-4,6-dimethyl-5-phenylazo) and related ligands show coordination through the thioenol S and cyano N atoms." " The Co(II), Ni(II), Zn(II) and Cd(II) complexes of lH-l,2,4-triazole-3-thiol and 3-amino-5-mercapto-1,2,4-triazole have IR spectra consistent with ligand coordination through the ring N and exocyclic S atoms." Rh, Ir, Pd and Pt complexes containing mono-, di- and trisubstituted thioureas, all show IR bands from -coordinated ligands." ... 

There were some literature reports on the reactions of T2,4-triazoles. 3-Bromo- and 3-iodo-N,S-dibenzyl-5-mercapto-l,2,4-triazoles 140 participated in Suzuki—Miyaura cross-coupling reactions with aryl, heteroaryl, and vinyl boronic acid derivatives to give 141, followed by deprotection with aluminum chloride to give 5-hetero(aryl)-3-mercapto-l,2,4-triazoles 142 (13TL4524). Multiple regioisomers of arylated 1,2,4-triazoles via C-H arylation could be obtained from judicious reactions of SEM- and THP-protected 1,2,4-triazoles (13JOC738). 

El-Sayed AM, Khodairy A (1998) Synthesis of new fused and spiroheterocycles derived from 4-amino-5-mercapto-3-trifluoromethyl-l,2,4-triazole. Phosphoras Sulfur Silicon 132 41—52... 

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