Thiourea 1,2,4-thiadiazolidines

Several related derivatives have also been utilized in this type of synthesis. Imino-chloromethanesulfenyl chlorides (184), prepared by the controlled addition of chlorine to isothiocyanates, react with amidines (161) to give 1,2,4-thiadiazolines (185) (71T4117). Chlorocarbonylsulfenyl chloride (186), prepared by the hydrolysis of trichloromethanesulfenyl chloride with sulfuric acid, reacted with ureas, thioureas and guanidines to give 1,2,4-thiadiazolidine derivatives (187) <70AG(E)54, 73CB3391). 

A similar transformation involving isocyanates instead of enamines has been reported. The imino thiadiazolidine 36 when reacted with methyl isocyanate affords a mixture of two compounds the bicyclic derivative 37 and the thiourea derivative 38 (Equation 10) <1997IJB399>. 

Type D synthesis, where the 3,4-CN bond is being formed, involves the reaction of thiosemicarbazones of aldehydes, ketones, and esters 97 with 3,3-pentamethyleneoxaziridine 98 to afford 5-imino-3,3-pentamethylene-l,2,4-thiadi-azolidines 99 (Equation 27). yV-Acylthioureas also undergo this transformation but, whereas this reaction is fairly general for thiosemicarbazones, only acetyl and benzoyl thioureas give 1,2,4-thiadiazolidines <1996CHEC-II(4)307>. There have been no new reports of type D syntheses since the publication of CHEC-II(1996). 

The reaction of 2,5-dimercapto-l,3,4-thiadiazolidine 34 with dialkylamines under Mannich reaction conditions gave N,S-aminomethylated thiadiazoles in 69-70% yields (Equation 24) <1998CHE1431>. With urea, thiourea, semicarbi-zide, or thiosemicarbazide, thiadiazolidine 34 gave N,N-aminomethylated thiadiazoles in 89-98% yields (Equation 25). 

The preparations of 1,2,4-thiadiazoles and 1,2,4-thiadiazolidines from thioureas are well known and have been summarized in three reviews those of Bambas,188 Sherman,189 and Kurzer.170 Contained in these reviews are discussions of the controversies that surrounded some of the products, notably Hector s bases, which resulted from oxidation of substituted thioureas.171,172 Subjects covered in the above reviews, but too extensive to outline in detail here, are the oxidation of amidinothioureas to 3,5-diamino-1,2,4-thiadiazoles (71),173,174 the oxidation of phenylthiourea175 and of substituted amidinothioureas176 to 3,5-diimino-l,2,4-thiadiazolidines (72, Hector s bases), the reaction of thiopseudoureas with trichloromethanesulfenyl chloride to form 3-alkylthio-5-chloro-l,2,4-thiadiazoles (73),177 the reaction of thiopseudoureas with sodium thiocyanate and bromine178 and the oxidation... 

Freund and Wolf10 reported that 2,4-diphenyl-l,2,4-thiadiazolidine-3,5-dithione was formed by heating l,3-diphenyl-2-thiourea with thiophosgene in benzene whereas, a 1,3-thiazetidine was produced at lower temperatures in ether (see Section II). Ohande181 has reported that 3,5-diamino-l,2,4-thiadiazoles are formed by the reaction of thiopseudoureas with carbon disulfide in the presence of bromine. Use has also been made of thioureas in the synthesis of 1,3,4-thiadiazolines (79) via reaction with the halohydrazones 78.185,186 The analogous reaction with solenoureas was recently reported by Bulka and Ehlers187 to yield 1,3,4-selenadiazolines. 

The reaction of trichloromethanesulfenyl chloride 617 with amidines 616 and a mild base is a general preparation for 5-chloro-l,2,4-thiadiazoles 618 <1965AHC(5)119>. Iminochloromethanesulfenyl chlorides 620 (from RNCS + C12) react with amidines 619 to give 1,2,4-thiadiazolines 621 <1971T4117>. Chlorocarbonylsulfenyl chloride 623 (prepared from trichloromethanesulfenyl chloride and sulfuric acid) reacts with ureas, thioureas, and guanidines to give 1,2,4-thiadiazolidine derivatives 624 (Scheme 274) <1973CB3391> (see also ). 

In an independent synthesis of both these isomeric products (38, 39), a (substituted) thiourea is condensed with a cyanamide or a carbodiimide (e.g., in acetone-hydrochloric add) which of the two products predominates is controlled in some degree by a choice of suitable conditions.55,56 The synthesis has been exemplified using arylcyanamides in conjunction with thiourea,56 1-alkyl-57 or 1,3-dimethylthiourea57 (see also Section f) it is of importance because the amidinothioureas (39) that are thus made accessible function as precursors of the 1,2,4-thiadiazolidines (31 etc.) (see Scheme 4). 

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