1.2.4- Dithiazolidine

Thiurets — see 1,2,4-Dithiazolidines, diimino-Thonzylamine antihistamine, 3, 153 Thorpe reaction benzothiophenes from, 4, 876 Thorpe-Ziegler cyclization, 2, 74 Three-membered heterocyclic compounds basicity, 7, 23... 

A number of ring systems have been converted into 1,2,4-thiadiazole derivatives. The most common include 5-imino-1,2,4-dithiazolidines, isoxazoles, oxadiazoles, and 5-imino-l,2,3,4-thiatriazolines. In general, a ring-opening reaction is followed by rotation and ring closure, or the heterocyclic ring may act as a masked 1,3-dipole which reacts with a suitable dipolarophile. 

In the 1,2,4-dithiazolidine series, 4-phenyl-3-aroylimino-5-methylimino-1,2,4-dithiazolidine (15) rearranges under the influence of benzoyl isothiocyanate into the 3-aroylimino-4-methyl-5-phenylimino-l,2,4-dithiazolidine (16) (78JOC4951). The Dimroth rearrangement is suggested to occur via a betaine as intermediate (Scheme IV.IO). It is of interest to mention that the isomerization of 15 into 16 was not observed with the Lewis acids aluminum trichloride or benzoyl chloride. 

The sulfur atoms in certain 1,2,4-dithiazolidines can be replaced by hydroxylamine to give 1,2,4-oxadiazoles <80PHA48>. 

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... 

A related cycloaddition/elimination reaction occurs when 5-imino-1,2,4-dithiazolidin-3-ones (300) or -3-thiones (306) are treated with phenylisocyanate to afford 2-phenyl-5-imino-1,2,4-thia-diazolidin-3-ones (307) (Equation (45)) <92JPR685>. 

Dithiazolidines containing o-quinonemethide structural units in the 3,5-positions (e.g. (99)) are converted by reagents with an activated CHj group into a range of condensed heterocyclic compounds not easily accessible otherwise (Scheme 14) <85S535,86PHA283>. 

Phenylthiosemicarbazones (198) of aromatic aldehydes and ketones give 1,2,4-dithiazolidines (199) with the same reagent, whereas those of aliphatic ketones produce 1,2,4-triazolines only (Equation (20)) <91JHC1957>. Aromatic and heteroaromatic thiodihydrazones (200) in the same reaction conditions afford 1,2,4-dithiazolidines (201) (Equation (21)) <91JHC1957>. 

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. 

Thioxo-1,2,4-dithiazolidines can be obtained from thioxo-l,2,4-thiadiazolidines by Dimroth rearrangement (Scheme 47) or reversibly by addition and elimination of acetone (Scheme 22). 1,2,4-Dithiazole type products are also obtained from thiocarbonyl isothiocyanates (154) by reaction with CI2 <84CHEC-I(6)897>, PhMgBr, Sj, or CS2. Other routes include reactions of carbonyl isothiocyanates and thiocarbonyl isocyanates with P4S10 or Sg <84Chec-I(6)897> and sulfonyl isocyanates with dialkyl thioketenes. Phenylisothiocyanate heated with N,C-disubstituted oxaziridines affords 3,5-diimino-l,2,4-dithiazolidines (226, 227). Other miscellaneous syntheses of 1,2,4-dithiazoline derivatives include cyclization of A7-thioacyl hexafluoroacetonimine to 5,5-bis(trifluoromethyl)-... 

Amino-1,2,4-dithiazole-5-thione may be used for corrosion inhibition of Cu-)-Zn powder mixture <86Mi 413-03) or for inhibition of polymer ageing <85URPl 142485) A-alkoxy derivatives inhibit corrosion of iron <91URP1650683,82MI413-06,82MI413-07). 1,2,4-Dithiazolidines (247 = H,... 

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>. 

Freund,168-160 formulating the oxides as substituted 1,2,4-thia-diazolidines (152) and the sulphides as 1,2,4-dithiazolidines (155), justified the assignment of unlike hetero-nuclei on the grounds that sulfides were also obtainable by the action of bromine on alkyl dithiocarbamates (see below), while oxides were unobtainable by the corresponding reaction of alkyl thiocarbamates. Hantzsch and... 

The oxidation of dithiobiuret and its homologs yields the so-called thiurets (for asummary, see ref. 134), for which a 1,2,4-dithiazolidine structure (319 and 320) is generally accepted. Their formulation as 3-thiono-l,2,4-thiadiazolidines (317 and 318) has been discussed,1 but the weight of the available evidence supports the cyclic disulfide structure (319 and 320)184 originally proposed.188... 

Substituted thiatriazoline-5-thiones are probably formed in the reaction between alkyl azides and phenyl isothiocyanate.66 In this case the reaction is conducted at 80-100° in the absence of solvent, and the primary products cannot be obtained. With two equivalents of phenyl isothiocyanate, 4-alkyl-3,5 -bis(pheny limino)-1,2,4-dithiazolidines are formed in 29-65% yield [Eq. (20)]. 

A classic example of this reaction is the Dimroth rearrangement, which is initiated thermally or in the presence of base catalysts and can usually occur with the retention or cleavage of the S-S bond depending on the nature of the substituents. The former pathway is typical of 3,5-diimino- and 5-imino-l,2,4-dithiazolidine-3-one derivatives and involves a rupture of one C-N bond, rotation of the N-C-N moiety around the S-C bond, and formation of a new 1,2,4-dithiazolidine derivative. The second pathway occurs when at least one N-substituent is an alkyl group and involves a rupture of the S-S bond, rotation of the N-C-S moiety around the N-C bond, and formation of the 1,2,4-thiadiazolidine derivative (Scheme 14) <1996CHEC-II(4)453>. 

Similar to the conjugated 1,2,4-dithiazole derivatives, 1,2,4-dithiazolidines are disposed toward nucleophilic attacks at carbon and sulfur atoms. Thus, 3,5-bis(arylimino)-l,2,4-dithiazolidine hydrobromides 83 are transformed into4//-3,5-bis(arylimino)-l,2,4-triazoles 84 at reflux with a hydrazine hydrate excess in ethanol (Equation 10) <2004MI534>. Aniline and benzylamine also attack 1,2,4-dithiazolidines 23 at 3,5-carbon atoms <1996CHEC-II(4)453>. 

Only a few examples of a nucleophilic attack at the nitrogen atom of 1,2,4-dithiazolidine derivatives are known. 5-Imino-l,2,4-dithiazolidine-3-thione gives tribenzyl-substituted 5-imino-l,2,4-thiadiazolidine-3-thione with an excess of boiling benzylamine <1996CHEC-II(4)453>. l,2,4-Dithiazolidine-3,5-dione 12 forms the potassium salt 11 under the action of KOH in ethanol or KH in MeCN (Scheme 15) <2000SL1622>. 

The unsubstituted nitrogen atom in 1,2,4-dithiazolidines is more prone to electrophilic reactions. Both the potassium salt 11 and the initial product 12 can participate in alkylation and acylation reactions. Alkylation of salt 11 with alkyl halides is carried out in DMF or MeCN and compound 12 can react with alkyl halides in MeCN in the presence of inorganic bases (NaH, Bu OK, AcONa, NaHCOj, CS2CO3) NaHCO( proved to be the base of choice. Yields of alkylation products 26 in some cases reach 85-90%. Compound 12 was acylated by benzoyl chloride in pyridine to form the iV-benzoyl derivative 25 (Scheme 15) <2000SL1622, 20030BC3015>. 

Thioamides of 3-oxoacids 118 are transformed into 1,2,4-dithiazolidines 29 by treatment with cerium ammonium nitrate (CAN) in MeOH or with CF3SC1 in CH2CI2 (Equation 16) <1996SC4165, 2001SC189>. The thermal conversion of 6/7-1,3,5-oxathiazine A-oxides 119 in refluxing benzene results in 1,2,4-oxathiazolines 20 with extrusion of R CHO. This reaction involves the heterodiene intermediate 120, which can be independently trapped by the reaction with EtOH (Scheme 32) <2003TL2517, 2004HAC175>. 

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