1,2,4-Thiadiazoles, mercapto

A similar conclusion has also been reached in the case of 5-mercapto-1,2,4-thiadiazoles 207 [76AHC(S1), pp. 405, 414 96CHEC-II(4)307] although the question remains open of which of the three possible thione forms is the energetically favored tautomer (Scheme 70). 

Type B syntheses are characterized by the reaction of an amidoxime 77 with carbon disulfide to afford 5-mercapto-1,2,4-thiadiazoles 78. The corresponding 5-amino derivatives 80 are obtained from the reaction of iV-sulfenylami-dines 79 with arylisothiocyanates (Scheme 8) <1996CHEC-II(4)307>. 

Amino and 5-amino-1,2,4-thiadiazoles both exist predominantly in the amino forms. The IR spectrum of 5-mercapto-1,2,4-thiadiazole does not show a clear SH absorption as would be expected for structure (10), therefore the thione tautomers (11) and (12) have been suggested (Scheme 6). Similarly IR evidence suggests that perthiocyanic acid exists as the dithione (13) as opposed to (14) <84CHEC-I(6)463>. 

Mono- and di-thiocyanato-1,2,4-thiadiazoles, obtained by the stepwise action of cyanogen bromide on barium 3,5-dimercapto-l,2,4-thiadiazole, and on 5-chloro- and 5-hydroxy-3-mercapto-1,2,4-thiadiazole, are somewhat labile. The structures of certain of their transformation products (e.g. mono- and di-sulfides), which may have one of several isomeric forms, are not fully elucidated. The reactivity of their cyano group, resembling that in cyanogen halides, is noteworthy it is easily removed by the action of alkalis, the parent thiol being regenerated.202... 

A reaction that is formally comparable to Thiemann s synthesis of 5-mercapto-1,2,4-thiadiazoles (141) from amidoximes (143) is the condensation... 

The action of trifluorobutenyl bromide (CF2=CFCH2CH2Br) on 3-phenyl-5-mercapto-l,2,4-thiadiazole and numerous analogs produces 5-(3,4,4-trifluoro-3-butenyl)thio derivatives (435), which are useful nema-tocides.344 The 5-alkylthio compound (436) is the product of the S-alkylation using l-(/ -chloro-2,4-dichlorophenetyl)imidazole.345 The formation of the monosulfide (437) from 3-isopropyl-5-mercapto-1,2,4-thiadiazole occurs under standard conditions.346... 

Corrosion Inhibitors, using mercapto-thiadiazoles which also give an extreme pressure/antiwear boost,... 

Blajiev, O. and A. Hubin, Inhibition of copper corrosion in chloride solutions by amino-mercapto-thiadiazol and methyl-mercapto-thiadiazol An impedance spectroscopy and a quantum-chemical investigation. Electrochimica Acta, 2004. 49(17-18) p. 2761-2770. 

Theoretically, a large number of materials may be applied as corrosion inhibitors for copper, but only a few of these have been thoroughly investigated. Azoles, especially triazoles, were studied as effective copper corrosion inhibitors (Lee and Nobe, 1986 Crundwell, 1992 Fiaud, 1995). Copper corrosion is reduced by mercaptobenzo-thia-zole (Weisstuch et al., 1971) through chemisorption, and by mercapto-thiadiazole through physical sorption (Chaudhary, 1997). Stricter environmental restrictions forced researchers to develop more environmentally friendly additives. 

With 2% of an EP sulphur additive (a di-mercapto-thiadiazole derivative). 

Thiadiazole, 2-amino-5-mercapto-azo dyes from, 1, 330 radioprotective agent, 6, 576 tautomerism, 6, 557... 

According to REM, hydrazine hydrate Is reacted with 2 mols of ammonium thiocyanate to produce 1,2-bislthlocarbamoyl) hydrazine which by loss of ammonia and rearrangement produces 5-amino-2-mercapto-1,3,4-thiadiazole. That compound is acetyied with acetic anhydride. 

Then, as described in U.S. Patent 2,55416, the 2-acetylamido-5-mercapto-1,3,4-thiadiazole is converted to the sulfonyl chloride by passing chlorine gas into a cooled (5°-10°C) solution in 33% acetic acid (66 parts to 4 parts of mercapto compound) used as a reaction medium. Chlorine treatment is continued for two hours. The crude product can be dried and purified by recrystallization from ethylene chloride. The pure compound is a white crystalline solid, MP l94°C,with decomposition, when heated rapidly. The crude damp sulfonyl chloride is converted to the sulfonamide by addition to a large excess of liquid ammonia. The product is purified by recrystallization from water. The pure compound is a white, crystalline solid, MP 259°C, with decomposition. The yield of sulfonamide was 85% of theory based on mercapto compound. 

Figure 17-12. Biocides for hydraulic fracturing fluids 2-mercaptobenzoim-idazole, 2-mercaptobenzothiazole, 2-mercaptobenzoxazole, 2-mercapto-thiazoline, 2,5-dimercapto-1,3,4-thiadiazole, and 2-imidazolidinethion.

Reaction of sodio 7-aminocephalosporanic acid with l-(lH)-tetrazoylacetic acid gave intermediate 27. Reaction of this last with 2-mercapto-5-methyl-1,3,4-thiadiazole led to the widely used parenteral cephalosporin, cefazolin (28). 

Mercapto-l,2,4-thiadiazoles exist as an equilibrium of tautomers with the equilibrium favoring the thione tautomer. They are acidic with a pA a of around 5. A variety of methylating agents (e.g., diazomethane, dimethyl sulfate and methyl iodide) give S-methylated products and no N-methylation has been observed. They are readily oxidized to sulfoxides and sulfones with either z-chloroperbenzoic acid or hydrogen peroxide in acetic acid <1996CHEC-II(4)307>. There have been no new publications on S-linked substituents since the publication of CHEC-II(1996). 

The enhanced reactivity of 5-halogeno-l,2,4-thiadiazoles over 3-halogeno-l,2,4-thiadiazoles has been mentioned before (see Section 5.08.7.1). Nucleophilic substitution at this center is a common route to other 1,2,4-thiadiazoles, including 5-hydroxy, alkoxy, mercapto, alkylthio, amino, sulfonamido, hydrazino, hydroxylamino, and azido derivatives. Halogens in the 3-position of 1,2,4-thiadiazoles are inert toward most nucleophilic reagents, but displacement of the 3-halogen atom can be achieved by reaction with sodium alkoxide in the appropriate alcohol <1996CHEC-II(4)307>. 

Oxidative cyclization of dithiobiuret under basic conditions provides bis(5-amino-l,2,4-thiadiazolyl)-3,3 -disulfide 92 via oxidative dimerization of the intermediate 5-amino-3-mercapto-l,2,4-thiadiazole 91. However, alkylation of disulfide 91 under basic conditions gives the thioalkyl-l,2,4-thiadiazole 93 (Scheme 9) <2003H(60)1401>. 

Amidines and amidoximes react with carbon disulfide and a mixture of carbon disulfide and sulfur to afford 5-mercapto-l,2,4-thiadiazole derivatives (see Section 5.08.9.3). 

Tautomerism was reviewed quite extensively in CHEC(1984) <1984CHEC(6)545> and CHEC-II(1996) <1996CHEC-II(4)379>. The tautomeric ability of the 2-mercapto-5-methyl-l,3,4-thiadiazole 9 was studied by its reaction with the electrophilic Cl3 FnCSCl <2003JP01>. 2-Mercapto-5-methyl-l,3,4-thiadiazole 9 was considered to exist mainly as the thione tautomer however, electrophilic substitution occurred on the thiol (Scheme 1). 

High-vacuum pyrolysis of 2,5-dimercapto-l,3,4-thiadiazole 34 and 2-mercapto-5-methyl-l,3,4-thiadiazole 9 performed between ambient and 800 °C gave products that were trapped by matrix-isolation techniques and characterized by IR spectroscopy. Pyrolysis of the dimercaptothiadiazole 34 gave HNCS, CS2, and HCN (Equation 2), whereas the thiadiazolethione 9 showed a more complex fragmentation pattern forming HNCS, CH3NCS, HCN, and CS2 (Equation 3) <2002J(P2)1620>. 

Halogenation of 2-methyl-l,3,4-thiadiazole 9 can be achieved under free radical conditions. Trichloro- and tribromomcthyl-l, 3,4-thiadiazolcs have been obtained by this method <1980LA1216>. Rapid and selective free radical monochlorination of the 2-mercapto-5-methyl-l,3,4-thiadiazole 9 was achieved using sodium hypochlorite under microwave conditions (Equation 27) <1998JCM586>. 

The sulfide groups in mesoionic 1,3,4-thiadiazolium salts are activated toward nucleophilic substitution. The mercapto substituent of the thiadiazolium salt 117 can be displaced by cyclohexylamine to afford the 2//-thiadiazol-imine 118 (Equation 37) <2004BML4607>. 

Scheme 44 also shows two further synthetic routes to [l,3,4]thiadiazolo[2,3-c][l,2,4]triazinones. Reaction of the 3-mercapto- or 3-methylsulfanyltriazinone 221 (R1 = H or R1 = Me) with a set of isothiocyanates was reported to give the 2-amino-substituted fused ring system 222 in medium to good yield (36-84%) <1997JHC1351>. Derivative 223 was described to undergo cyclization to a fused thiadiazole 224 by treatment with carbon disulfide in the presence of potassium hydroxide in ethanol <2001PHA376>. 

Amino-5-mercapto-l,3,4-thiadiazole was reacted with EMME in boiling DMF for 16 hr to afford thiadiazolo[3,2,-n]pyrimidine-6-carboxylate (1131, X = S, R = SH) in 80% yield [85EUP150507]. 

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