1.2.5- Thiadiazole reductive cleavage

Isothiazoles are reductively desulfurized by Raney nickel, e.g. as in Scheme 31 (72AHC(l4)l). 1,2,5-Thiadiazoles are subject to reductive cleavage by zinc in acid, sodium in alcohol, or Raney nickel, e.g. Scheme 32 (68AHC(9)107). 

The 1,2,5-thiadiazole ring is susceptible to reductive cleavage by a number of reagents including zinc and mineral acids,sodium and alcohol,and Raney nickel. Reduction occurs at the N—S bond (also the site of cleavage of 1,2,3- and 1,2,4-thiadiazoles) with formation of hydrogen sulMe and regeneration of the NCCN portion of the molecule in a reduced form. This property has been employed as a method of structure proof of 1,2,5-thiadiazoles in a number of cases. 

Reductive Removal of Mercapto-groups. 2-Mercapto-l,3,4-thiadiazole, and the parent thiadiazole, which were hitherto only accessible by multi-stage syntheses, may readily be prepared from 2,5-dimercapto-l,3,4-thiadiazole by the successive removal of its mercapto-groups, by reductive cleavage of carbon-sulphur bonds with sodium in liquid ammonia. The 2-amino-5-mercapto-compound is similarly convertible into 2-amino-l,3,4-thiadiazole (up to 65%). ... 

Thiadiazolidines cannot be prepared by reduction of the corresponding thiadiazoles or thiadiazolines because cleavage of the ring would occur in preference to reduction as a consequence of the harsh conditions required. No preparations of 1,2,4-thiadiazolidines have been reported. 

Reactions of 1,2,4-thiadiazoles with radicals and electron deficient species are virtually unknown. Catalytic and dissolving metal reductions usually result in S—N bond cleavage. For example, the 5-anilino-3-hydroxy derivative (51) gives a good yield of l-phenyl-2-thiobiuret (52) on Zn-HCl reduction (Scheme 27). Reduction of the diamino derivative (53) gives amidinothiourea (54) from which it may be prepared by oxidation (Scheme 28). Under similar conditions, cleavage of the 3,5-diphenyl derivative (55) results in loss of sulfur and formation of benzylbenzamidine (56 Scheme 29). Reduction of 5-alkylamino-or 5-arylamino-3-alkylthio derivatives (57) with H2S in pyridine-triethylamine or sodium in liquid ammonia yields 1-substituted dithiobiurets (58 Scheme 30). 

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