Trichloromethylsulfenyl 1.2.4- thiadiazoles

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 condensation reaction of cyclic amidines with trichloromethylsulfenyl chloride yields sul-fenamides, which afford 5-arylimino-l,2,4-thiadiazolines on treatment with aromatic amines <84CHEC-I(6)463>. An example of this type of reaction starting from 2-amino-4-arylthiazoles (271) affords 3/f-thiazolo[2,3-c]-l,2,4-thiadiazoles (272), via the sulfenamide (270) (Scheme 60) <88IJC(B)501>. 

A useful method for the synthesis of 5-chloro-l,2,4-thiadiazoles (206) is the reaction of amidines with trichloromethylsulfenyl chloride (see Equation (30)). 3-Halo derivatives (349) (X = Cl, Br, I) (Equation (57)) have been obtained in moderate yields from the corresponding amines (348) via the Sandmeyer-Gatterman reaction <84CHEC-I(6)463>. 3-Chloro-l,2,4-thiadiazolin-5-ones (350) and (351) can be prepared by reacting chlorocarbonylsulfenyl chloride with carbodiimides or cyanamides respectively (Scheme 79) <84CHEC-I(6)463>. 

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. 

In a series of publications (75JOC2600, 70JOC1965, 73JOC3087), Potts and coworkers have reported that cyclic amidines (290) readily condense with trichloromethylsulfenyl chloride (329) to yield the sulfenamides (330 Scheme 119). Treatment of the latter compounds with aromatic amines in the presence of triethylamine results in cyclization, possibly via an intermediate such as (331), to produce bicyclic products of type (332). Heterocycles (290) which have been used successfully in this reaction include 2-amino-l,3,4-thiadiazoles, 3-aminopyridazines, 2-aminopyrimidines, 2-aminopyrazines, 2-aminopyridines, 3-aminoisoxazoles and 5-amino-1,2,4-thiadiazoles. The sulfenamide derivative (330) of 2-aminopyridine also was found to react with sodium sulfide and with diethyl malonate to produce (333) and (334) respectively. Attempts to hydrolyze (332) to (295) under acidic conditions failed. 

The reactions of 3-amino-5-methylisoxazole with l,3-bis-(dimethylamino)-2-azapropene 27 (94JHC535), isocyanate (87JHC501), and trichloromethylsulfenyl chloride (75JOC2600) gave isoxazolo[2,3-a]l, 3.5-triazincs 28, 29, and isoxazolo [3,2-c]thiadiazoles 30, respectively (Scheme 14). 

The cyclocondensation of amidines with trichloromethylsulfenyl chloride furnishes 5-chloro-1,2,4-thiadiazoles 4 ... 

With regard to the syntheses from fluorinated acyclic precursors, an approach to fluorinated 1,2,4-thiadiazoles utilized the oxidative heterocyclization of fluorinated thioacyl-amidines. For example, trilluoroacetamidine and ethyl chlorothiocarbonate will form the open-chain intermediate 132 which, upon oxidation with bromine, leads to 5-ethoxy-3-tiifluoromethyl-l,2,4-thiadiazole 133 (Scheme 35) [63], A direct heterocyclization into the thiadiazole 137 takes places from the reaction of the fluorinated (V-bromotrifluoroacetamidine 134, prepared by selective bromination of the corresponding trifluoroacetamidine 135, with ethyl xanthate [64], In addition, the 3-perfluoropropyl-5-chlorothiadiazole 137 is obtained in 52 % yield from the reaction of heptafluorobutyramidine hydrochloride 136 with trichloromethylsulfenyl chloride in the presence of a base (Scheme 35) [62],... 

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See also in sourсe #XX -- [ , ]

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