Thiadiazolidine

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). 

Thione S-imides, such as the fluorenethione S-tosylimide (68), have been known for about ten years. Saito and co-workers93 have studied the cycloaddition reactions of 68 with compounds containing homonuclear and heteronuclear double bonds. In almost every case the imide (68) reacted as a 1,3-dipole with alkenes, for example, isothiazoline derivatives (such as 69) were formed and with azines the 1,2,4-thiadiazolidine derivatives (70) were produced.93... 

The number of X-ray structures published since the publication of CHEC-II(1996) has increased, underlining the importance of this technique in structure elucidation. The structure of a number of 1,2,4-thiadiazoles and 1,2,4-thiadiazolidines has been determined by X-ray techniques and they are listed in Table 1. The first preparation of an A7-oxide derivative of a 1,2,4-thiadiazole 2 has been reported. The X-ray structure of compound 2 shows that it has a nearly planar ring this conformation is stabilized by hydrogen bonding with the carboxamide group <1999J(P1)2243>. 

The relationship between the structure of 1,2,4-thiadiazolidines and their H NMR spectral solvent effects has been studied by measurement of the NMR chemical shift differences (Av) of 39 derivatives in various solvents (CgDg, CCU) for methyl or methylene groups attached to an sp2-hybridized nitrogen, Av correlates linearly with Hammett a constants and for those attached to an sp3 4-hybridized nitrogen, with Taft a° constants <1982AHC285>. 

The 5-amino-1,2,4-thiadiazolidine 29 can be acylated with acetic anhydride in pyridine at N-2 to give the iV-acyl derivative 30 (Equation 7) <1998JHC1435>. 

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. 

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). 

X-ray crystallographic techniques have greatly aided progress in deducing the chemistry of 1,2,4-thiadiazoles. The structures of a number of 1,2,4-thiadiazoles and 1,2,4-thiadiazolidines have been determined by x-ray techniques, and are listed in Table 1. 

Ethyl-4-phenyl-5-phenylimino-1,2,4-thiadiazolidin-3-thione 86BCJ987... 

Ethyl-5-ethylimino-2-phenyl-3-phenylimino-1,2,4-thiadiazolidine 80AX(B)2703... 

Carbon-13 NMR spectral data have appeared more widely in the literature over the past 12 years. The C NM R chemical shifts for a variety of 1,2,4-thiadiazoles and 1,2,4-thiadiazolidines derivatives are listed in Table 2. 

In 1991 L abbe reported that the 1,2,4-thiadiazolidine (71) and the 1,2,4-dithiazolidine (72) are interconvertible in the presence of electrophilic nitriles and give the 1,2,4-thiadiazoline-5-ones (73) as products (Scheme 18) <9UOC3268>. It is suggested that the reaction goes by a consecutive... 

The IR spectrum of 1,2,4-thiadiazolidine-3,5-dione indicates that the dithione structure (13) predominates. However, the dithione can be readily dialkylated on sulfur and treatment with 1-chloro-4-nitrobenzene in aqueous sodium hydroxide yields (150) (Scheme 33) <89EUP330020>. 

Two products are isolated from the reaction of 4-methyl-5-methylimino-l,2,4-dithiazolidine-3-thione (108) with nitriles (Scheme 23) its 1,2,4-thiadiazolidine isomer (109) and a 1,2,4-thia-diazolidine derivative incorporating the nitrile unit (112). A sequence of 1,3-cycloaddition-elim-ination steps via heteropentalene intermediates is proposed for the process <9lJOC3268). 

A reversible rearrangement of 1,2,4-thiadiazolidine (109) (Scheme 22) occurs in acetone with participation of the latter apparently via heterapentalene intermediate formed by reversible 1,3-cycloaddition of the carbonyl group to the S=C—S entity <92JHC69>. 

Oxaziridines (235) heated with phenylisothiocyanate at 80-100°C afford 1,2,4-dithiazolidines (236), (237) and 1,2,4-thiadiazolidines (238) in proportions depending on R (Equation (27)). At a higher temperature (105-110°C, R = Bu, c-QHn) the reaction takes another course <74JOC957, 86JOC407,86BCJ987>. Thiaziridinimine (239) is postulated as an intermediate reacting with a second molecule of PhNCS. 

The sultam (146) yields the 1,2,4-dithiazolidine (174), thiazolidine (175) or 1,2,4-thiadiazolidine derivatives (176) on heating with an excess of several heterocumulene dipolarophiles (Scheme 29). It is formally acting as a masked 1,3-dipole resulting from elimination of the sulfene moiety (PhCH SOj) <78JOC4951>. 

Compounds of molecular formulae (RNCS)20 and (RNCS)2S, for which 1,2,4-thiadiazolidine structures have been considered, are obtainable from isothiocyanate esters on oxidation the latter series is also accessible from dithiocarbamates. 

The experimental evidence as a whole suggests that both isothiocyanate oxides and sulfides, in the form of their salts, possess the dithiazolidine structures 153 and 155, respectively the lower alkyl isothiocyanate oxides when liberated rearrange to the 1,2,4-thiadiazolidines (152), but the higher homologs do not. In the isothiocyanate sulfides,... 

Isomerization of this cyclic disulfide (see above) affords the 1,2,4-thiadiazolidine (159), also obtainable directly from sodium methyl dithiocarbamate by conveying the wet, finely powdered salt under oxidative conditions through a pneumatic dryer.166 The production of alkyl (and phenyl) homologs by this procedure is claimed in the patent literature,166 but no physical constants are given. It is recalled that the isomerization 158->159 had previously been thought to be confined to the methyl homologs.160,164... 

The use of Hector s base (5-imino-4-phenyl-3-phenylimino-1,2,4-thiadiazolidine) as a sensitive reagent for carbon disulfide, and the nature of the product34,60 formed by the interaction of these compounds have been discussed by Feigl et ol.237... 

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