1,2,4-Thiadiazole, 5-chloro-3-mercapto

Amidines are converted into 1,2,4-thiadiazoles by reaction with isothiocyanates, iminosulfenyl chlorides, di- and trichloromethyl sulfenyl chlorides, and carbon disulfide in the presence of sulfur <82AHC(32)285> for example, 5-mercapto-3-methyl-l,2,4-thiadiazole (205) is obtained by the treatment of acetamidine with carbon disulfide and sulfur under basic conditions (Equation (29)) <85JAP85255783>. A useful method for the synthesis of 5-chloro-l, 2,4-thiadiazole (206) (R = 6-methyl-2-pyridyl) involves the reaction of amidines with trichloromethylsulfenyl chloride (Equation (30)) <91JAP9183590>. 

The unstable sodium salt of 5-chloro-3-mercapto-l,2,4-thiadiazole (336)151 reacts also with cyanogen bromide forming 5-chloro-3-thio-cyanato-l,2,4-thiadiazole (337).202 The sparingly soluble neutral sodium salt of 5-hydroxy-3-thiocyanato-l,2,4-thiadiazole (339) is similarly obtained (336->338->339) its free acid, like other 5-hydroxy-l,2,4-thiadiazoles, is fairly strong, but unstable.202... 

PhCH2), obtained in their turn by treatment of 3-alkyl(or aralkyl) thio-5-chloro-l,2,4-thiadiazoles (344 R = Me or PhCH2) with ammonium sulfide.91 Additional support in favor of structure 340 for perthiocyanic acid is the alternative production of its disodium salt (343) from 5-chloro-3-mercapto-l,2,4-thiadiazole (344 R = Na) and sodium sulfide.151... 

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... 

Amidines (282 R = H) also condense with carbon disulfide in the presence of sulfur to produce 5-mercapto-l,2,4-thiadiazoles (17) in reasonable yields, as indicated in Scheme 101 (68BRP1116198). A general method for the synthesis of 5-chloro-l,2,4-thiadiazoles (289 X = Cl) involves the reaction of amidines with trichloromethylsulfenyl chloride (288 X = Cl) in the presence of a base under mild conditions (Scheme 102) (65AHC(5)119). A variety of 3-substituted thiadiazoles (118) are obtained when dichloromethylsulfenyl chloride (288 X = H) is used in this reaction. 

C8H6CIN04 methyl 5-chloro-2-nitrobenzoate 51282-49-6 18.00 1 4530 1 12908 C8H6N2S3 5-mercapto-3-phenyl-2H-1,3,4-thiadiazole-2-t 17654-88-5 25.00 1.4341 2... 

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... 

The interaction of sodium perthiocyanate (438) and suitable bifunctional dihalides readily produces polymers (444) which are claimed to be useful catalysts in the production of polyurethane foams. The use of l,4-di(chloro-methyl)benzene in ethanol, for example, gives 444 (R = p-CH2C6H4CH2, terminating in p-CH2C6H4CH2OEt, mol wt 2960) in 90% yield.354 5-Mercapto-3-methylthio-1,2,4-thiadiazole yields the tin-containing derivatives 445 (R = Bu, Ph, or cyclohexyl n = 1-3) on treatment with alkyltin halides in tetrahydrofuran.355... 

Chlorolysis. The action of chlorine on mercapto-l,2,4-thiadiazoles yields sulfenyl chlorides, sulfonyl chlorides, or chloro compounds, depending on the nature of the starting materials and the experimental conditions.147 Thus treatment of 3-tert-butylthio-l,2,4-thiadiazole with one mole of chlorine yields bis(l,2,4-thiadiazol-3-yl) disulfide (446) as a stable colorless solid. An excess of chlorine converts this to the 3-sulfonyl chloride (447), and further, with loss of sulfur dioxide, to the 3-chloro compound (448). Under appropriate conditions, the chlorolysis (to 448) may be performed in one operation (45%). The 3-sulfonyl chloride (447) yields sulfonamides nearly quantitatively the 3-chloro substituent in 448 is relatively inert (see Section IV.B).147... 

Acetamido-5-mercapto-l, 3,4-thiadiazole is prepared as described under acetazolamide. This on treatment with/>-chlorobenzyl ehloride forms the corresponding />-chloro benzyl mercapto derivative, which when reacted with methyl bromide in the presenee of sodium methoxide yields the acetylamino thiadiazoline derivative. On oxidation with aqueous ehlorine it gives rise to the 2-sulphonyl chloride derivative which finally yields methazolamide on amidation with ammonia. 

Further examples of 5-mercapto-triazoles 59 and bis-triazolo[l,3,6]thiadia-zepines 60 have been reported by these authors [60]. Compounds 59 and 60, resulting from one or two Dimroth rearrangements, respectively, were obtained in one step by ccaidensation of 1,2-phenylenediamine with 5-chloro-l,2,3-thiadiazoles 56. The product distribution is highly dependent upon the reaction time and the presence of EtsN (Scheme 19). Without base, only 59 was obtained, whereas in the... 

---