2.4 Dithiobiuret

Treating 5.5 g of 2-amino-4,5-dimethylthiazole HCl with 0.66 g of solid sodium hydroxide 15 min at 220°C yields 53% of 4.4. 5.5 -tetramethyT 2,2 -dithiazolylamine, whose structure w as proved by identification with the produa obtained from the reaction between dithiobiuret and 3-bromo-2-butanone (467). This result is comparable to the reaction between 2-aminopyridine and its hydrochloride to yield bis(pyridyl-2)amine (468). Gronowitz applied this reaction to 2-aminothiazole, refluxing it with its hydrochloride 4 hr in benzene and obtained the dimeric 2-aminothiazole (236). He proposed a mechanism (Scheme 143) that involves the addition of a proton to the 5-position of the ring to give 234. The carbocation formed then reacts on the 5-position of a second... 

TABLE IM9. DITHIAZOLYLAMINES FROM DITHIOBIURET AND a-HALOCARBONYL COMPOUNDS... 

Dithiobenzoic acid metal complexes, 2, 646 colours, 2, 646 Dithiobiuret metal complexes, 2, 640 Dithiocarbamates chelating resins mineral processing, 6,826 Dithiocarbamic acid metal complexes, 2,585 amine exchange, 1,428 photographic emulsions, 6,98 nickel poisoning, 6,768 tellurium(Il) complexes photothermography, 6,121 Dithiocarbazic acid metal complexes, 2,803 Dithiocarbimic acid metal complexes, 2,588 Dithiocarbimic acid, cyano-metal complexes, 2,808 Dithiocarboxylic acids metal complexes, 2,646 Dithiodiacetic acid metal complexes, 2, 806 Dithiodiketones... 

Oxidative cyclization of dithiobiuret under basic conditions provides bis(5-amino-l,2,4-thiadiazolyl)-3,3 -disulfide 92 via oxidative dimerization of the intermediate 5-amino-3-mercapto-l,2,4-thiadiazole 91. However, alkylation of disulfide 91 under basic conditions gives the thioalkyl-l,2,4-thiadiazole 93 (Scheme 9) <2003H(60)1401>. 

The sulphur atoms in dithiobiuret can be successively alkylated. It is therefore possible to synthesise 1,5-disubstituted biguanides carrying unlike substituents by the stepwise alkylation and replacement of the alkylthio-groups of dithiobimet, as has been described (295) for Paludrine (XXVIII, R = p-ClCeH4). 

The reaction has been extended to the synthesis of the analogous 3-alkylthio heterocycles (123) from the appropriate dithiobiurets (122).132 1-Substituted 2,4-dithiobiurets (125), unlike their monothio-biuret analogs (118), are unsuitable as precursors of 1,2,4-thiadiazoles, since in any oxidation the two thiol groups may be expected to react preferentially, resulting in the formation of cyclic disulfides (126). The formulation of such oxidation products as 1,2,4-thiadiazoles has indeed been discussed by Bambas1 however, the available evidence133 favors the cyclic disulfide structure.134... 

Oxidative cyclization of the isomeric 1 -substituted substituted amino group in the ring formation and may therefore be expected to occur less readily.1 2 This is confirmed by the observation139 that oxidation of 1,5-diaryl- S,2-ethylisodithiobiurets (127 R = R = aryl ... 

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... 

Treatment of 5-alkyl(or aryl)amino-3-alkylthio-l,2,4-thiadiazoles with hydrogen sulfide in pyridine-triethylamine, or with sodium in liquid ammonia, yields 1-substituted dithiobiurets.182 Since, in the... 

Fromm12 proposed that l,3-diazetidine-2-thiones were the products of the reaction between dithiobiurets and aldehydes or ketones, which he called aldurets and keturets, respectively. These structures were subsequently shown to be hexahydrotriazines by Fairfull and Peak.13 Kurzer,3 in his review of dithiobiurets, summarized the structural work on aldurets and keturets. Dixon and Taylor14 claimed that 1,3-diazeti-dine-2-thiones wrere the products of the acid-catalyzed treatment of... 

Dithiobiurets react with a-halo ketones79-82 or aldehydes (generated in situ)63 to yield 2-thiureidothiazoles (40), which can be converted in two steps to 2-guanidinothiazoles.81 However, Beyer and Hantschel81 found that 2-guanidinothiazoles could be more conveniently prepared via the reaction of 1-amidino-2-thiourea with a-halo ketones or aldehydes. 

Iwataki83 reported that l,l-dimethyl-2,4-dithiobiuret formed 3-(N, iVr-dimethylthiocarbamoyl)-2-iminothiazolidin-4-one upon reaction with chloroacetyl chloride in acetone in the presence of pyridine however, the same reaction with sodium acetate used as a base produced 2-(3,3-dimethylthiureido )-2-thiazolin-4-one.83... 

In a series of papers, Fromm and co-workers,12,64,188,189 beginning in 1893, showed that dithiobiurets could be oxidized with agents such as ferric chloride or halogens to salts of 3,5-diimino-l,2,4-dithiazolines (80) or 3-amino-5-imino-5/f-l,2,4-dithiazoles (81). These heterocycles were named thiurets by Fromm, and that term has persisted in the later... 

Formaldehyde has been employed to prepare analogs of 159 with a higher degree of saturation. Thus 160 may be made by treating 1,1,5-trimethyl-2,4-dithiobiuret with refluxing aqueous formaldehyde,197 and... 

Less useful preparations of 1,3,5-thiadiazines in which they are formed as components of mixtures include that of Chase and Walker.262 They isolated a thiadiazine as a product of the reaction of thiourea, bromine, and p-chlorophenylacetonitrile in acetone. The function of the nitrile, which was not incorporated into the product, is not apparent. The product of a similar reaction, without the nitrile, was assigned a dithiazine structure by Baumann.304 Oliver and Stokes202 also reported that a 1,3,5-thiadiazine is formed among the myriad of identified products of the 15-month air oxidation of l,l,5,5-tetramethyl-2,4-dithiobiuret. 

Dithiobiuret complex. X-Ray structure shows PdS4 42 planar, ligands n on-planar... 

Dithiobiuret (28 dtbH) by loss of a proton from its iminothiol tautomer (29) forms neutral complexes [M(dtb)2] (M =Ni, Pd, Pt, Cu and Cd) the nickel complex is diamagnetic.81 In the complex [Pd(dtb)2] die four sulfur atoms are arranged in approximately square-planar arrangement with a mean Pd—S distance of 2.295 A.82... 

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