Thiadiazolidines synthesis

The problem of the synthesis of highly substituted olefins from ketones according to this principle was solved by D.H.R. Barton. The ketones are first connected to azines by hydrazine and secondly treated with hydrogen sulfide to yield 1,3,4-thiadiazolidines. In this heterocycle the substituents of the prospective olefin are too far from each other to produce problems. Mild oxidation of the hydrazine nitrogens produces d -l,3,4-thiadiazolines. The decisive step of carbon-carbon bond formation is achieved in a thermal reaction a nitrogen molecule is cleaved off and the biradical formed recombines immediately since its two reactive centers are hold together by the sulfur atom. The thiirane (episulfide) can be finally desulfurized by phosphines or phosphites, and the desired olefin is formed. With very large substituents the 1,3,4-thiadiazolidines do not form with hydrazine. In such cases, however, direct thiadiazoline formation from thiones and diazo compounds is often possible, or a thermal reaction between alkylideneazinophosphoranes and thiones may be successful (D.H.R. Barton, 1972, 1974, 1975). 

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). 

Several examples of 1,2,4-thiadiazolidin-3-one 5,5-dioxides 191-194 were isolated as by-products in the synthesis of sulfonopeptides. These are formed by refluxing in benzene or toluene the corresponding acylazides. These sulfonyl-hydantoins are extremely labile in protic solvents (96T(52)5303). 

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 5(4H)-oxazolones (32) and miinchnones with triphenylvinylphos-phonium bromide (33) provides a mild synthesis of substituted pyrroles (34) (Scheme 11). The cycloaddition-elimination reactions of 5-imino-l,2,4-thiadiazolidin-3-ones with enamines and ester enolates produce 2-iminothiazolidines. " Chiral isomtinchnone dipoles show jr-facial diastereoselectivity with IV-phenyl- or A -methyl-maleimide in refluxing benzene. ... 

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. 

Three-membered rings should in principle be accessible by reaction of heteroaldehyde and -ketone complexes with Q sources. This was verified by the synthesis of the thiirane complex 143 from thiobenzaldehyde complex 99a and diphenyl diazomethane [Eq. (30)]. The reaction was assumed to proceed via a 1,3,4-thiadiazolidine complex as the intermediate that loses dinitrogen to give 143.254... 

Thiadiazolidines cannot be prepared by catalytic or chemical reductions. Reagents vigorous enough to reduce the double bonds in a 1,2,4-thiadiazole ring also cleave the ring (see Section 4.25.3.1.8). No other synthesis of 1,2,4-thiadiazolidines has been reported. 

This is the most widely used procedure for the synthesis of thiadiazoles, thiadiazolines, thiadiazolidines and mesoionic thiadiazoles. It is classified into the following subsections. 

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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