1.3.4- Thiadiazole, 2-trichloromethyl

Bis(ethoxycarbonylamino)-l, 2,4-thiadiazole 4-Methyl-3-trichloromethyl-l,2,4-thiadiazolin-5-thione 4-Methyl-3-(/i-toluenesulfonyl)-l,2,4-thiadiazolin-5-thione 4-Methyl-3-ethoxycarbonyl-l,2,4-thiadiazolin-5-thione... 

Amidines and cyclic amidines are also converted into 1,2,4-thiadiazoles by reaction with isothiocyanates, imino-sulfenyl chlorides, di- and trichloromethyl sulfenyl chlorides, and carbon disulfide in the presence of sulfur. Ureas, thioureas, guanidines, carbodiimides, and cyanimides react with chlorocarbonylsulfenyl chloride to produce 1,2,4-thiadiazol-5-one derivatives in another example of a type B synthesis <1996CHEC-II(4)307>. 

A useful method for the synthesis of 5-chloro-l,2,4-thiadiazoles 125 is the reaction of amidines with trichloromethyl-sulfenyl chloride (Equation 34). 

Ethoxy-3-trichloromethyl-l,2,4-thiadiazole has excellent pesticidal and fungicidal properties. It is a commercial product, whose most common trade name is Terrazole. 

Reaction of 5-trichloromethyl-1,2,4-thiadiazoles with secondary amines leads to amides. For example, treatment of (84) with piperidine gives (86) which presumably arises by nucleophilic displacement of chloride ion from the trichloromethyl group, followed by hydrolysis during work up of the resulting dichloro compound (85) (Scheme 21) <86PS(26)151>. 

The excellent pesticidal and fungicidal properties of 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole (363) are well known <82AHC(32)285). It is a commercial product and is marketed under a variety of names of which Terrazole is the most common. Since 1984, a variety of 1,2,4-thiadiazole derivatives have been found to possess fungicidal activity. Thus, compounds such as (364), (365), and (366) and... 

Chemical Name 5-ethoxy-3-(trichloromethyl)-l,2,4-thiadiazole ethyl 3-trichloromethyl-l,2,4-thiadiazolyl ether Uses as fungicide for control of Phytophthora and Pythium spp. in cotton, ornamentals, vegetables, groundnuts, cucurbits, tomatoes, and other crops also used as a nitrification inhibitor in maize, cotton and wheat. 

A wide variety of reagents have been used to convert amidines (282) into 1,2,4-thiadiazoles. Treatment of (282) with sodium hypochlorite followed by potassium thiocyanate at pH 3 produces 5-amino derivatives (284) in moderate to good yields (Scheme 98). In one example an unstable intermediate (283 R = OMe, R = H) was isolated but not fully characterized (65AHC(5)119). Products of type (285) are obtained when amidines are treated with iminochloromethylsulfenyl chlorides (269 Scheme 99) (71T4117). When R is aryl (285) is the exclusive product whereas a mixture of isomers is obtained when R is aroyl. 5-Amino-l,2,4-thiadiazoles related to (284) and (285) also are formed in good yields when (V-haloamidines are treated with isothiocyanates. Thus, 5-methylamino-3-trichloromethyl-1,2,4-thiadiazole (287) is obtained in 73% yield from the reaction of A-bromotri-chloroacetamidine (286) with methyl isothiocyanate (Scheme 100) (78USP4107377). 

Similar reactions have been carried out with amidines (67NEP6610627). Thus tri-chloroacetamidine (309) reacts with chlorothioformate esters to produce thioacyl products (310) which are readily oxidized to 5-alkoxy-3-trichloromethyl-l,2,4-thiadiazoles (311). The yields in both steps are about 80% (Scheme 111). The bromine oxidation of N-thiocarbamyl derivatives (312) of cyclic amidines (2-aminopyridine, 2-aminothiazole, 2-aminopyrimidine) yields thiadiazolium salts (313) (71JPR1148). In the 2-aminopyridine series, products of type (230 Scheme 81) are obtained in 20-73% yield when R is an ethoxycar-bonyl group (750PP55). 

Dialkyl-l,3,4-thiadiazoles are prepared in high yield by the one-pot reaction between an aldehyde, hydrazine hydrate and elemental sulfur (Scheme 32). Chlorination of the 2,5-dimethylthiadiazole yields the bis(trichloromethyl) derivative which undergoes a wealth of reactions with various nucleophiles (80LA1216). 

A trichloromethyl group can be converted by antimony trifluoride into a trifluoromethyl group in the 1,2,4-thiadiazole series (Scheme 121). 

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