1, 2, 4-Thiadiazole-5-sulfonic acids

In another variation of a type E synthesis, thioamides or thioureas condense with /V,/V-dimcthylacylamide dimethyl acetal to give imino compounds which react with amino-transfer reagents like hydroxylamine-O-sulfonic acid and mesitylsulfonyloxyamine (MSH) to give 3,5-substituted-l,2,4-thiadiazoles in excellent yields <1996CHEC-II(4)307>. There have been no new reports of type E syntheses since the publication of CHEC-II(1996). 

Etaconazole heterocyclic nitrogen, triazole Ethalfluralin dinitroaniline Ethametsulfuron sulfonyl urea Ethephon phosphoro organic, phosphonic acid Ethidimuron urea, thiadiazole, sulfone Ethiofencarb carbamate... 

Sulfonic acids of simple 1,3,4-thiadiazoles appear not to have been prepared. The dipotassium salt of the 2,5-disulfonic acid was synthesized as early as 1899 by Busch and Ziegele by oxidation of the dipotassium salt of 2,5-dimercapto-l,3,4-thiadiazole with potassium permanganate. In the same way Petri and Glemser prepared 5-hydroxy-2,2 -azo-l,3,4-thiadiazole-5 -sulfonic acid dipotassium salt (125) from 2,2 -azo-l,3,4-thiadiazoline-5(4)-thione (76). 

Hydroxylamino-4,5-dihydroimidazolium-<9-sulfonate 303 is prepared by reacting 2-chloro-4,5-dihydroimidazole with hydroxylamine-O-sulfonic acid. Reaction of 303 with carbon disulfide in the presence of triethylamine presumably proceeds via intermediate 304 to yield the 6,7-dihydro-5//-imidazo[2,l-c][l,2,4]thiadiazole-3-thione 305 by a tandem nucleophilic addition-electrophilic amination reaction <03JOC4791>. In an interesting photochemical reaction, irradiation of 5-phenyl-1,2,4-thiadiazole 306 results in the formation of benzonitrile 307 <03JOC4855>. 

Several Cr111 complexes with activated amido donor ligands (e.g., amides of carboxylic or sulfonic acids) have been described, but none of them have been crystallographically characterized.132,479 Complexes of Cr111 with 2-sulfonamide-1,3,4-thiadiazol derivatives act as potent inhibitors of carbonic anhydrases and may have potential use as anti-inflammatory or antidiabetic drugs.479,480... 

When a sulfonamide reacts with aqueous acid or aqueous hydroxide, the amine (or ammonia) is released along with the parent sulfonic acid. Butanesulfonamide (191), for example, reacts with aqueous hydroxide (followed by an acid neutralization step) to give butanesulfonic acid (190) and ammonia. Sulfonamides are quite stable molecules and they are used in a variety of applications, particularly those sulfonamides derived from benzene derivatives (see Chapter 21). Sulfanilamide (192), for example, is a potent antibacterial agent and isobuzole (193), with the formal name of JV-(5-isobutyl-l,3,4-thiadiazol-2-yl)-p-methoxy-benzenesulfonamide, has hypoglycemic (antidiabetic) properties. 

Mercapto-l,2,4-thiadiazoles exist as an equilibrium of tautomers with the equilibrium favoring the thione tautomer. They are acidic with a pA a of around 5. A variety of methylating agents (e.g., diazomethane, dimethyl sulfate and methyl iodide) give S-methylated products and no N-methylation has been observed. They are readily oxidized to sulfoxides and sulfones with either z-chloroperbenzoic acid or hydrogen peroxide in acetic acid <1996CHEC-II(4)307>. There have been no new publications on S-linked substituents since the publication of CHEC-II(1996). 

Thiadiazole sulfides are readily oxidised to the corresponding sulfoxides and sulfones. For example, the sulfide (139) is converted into the sulfoxide (140) (Equation (19)) using m-chloroperbenzoic acid <84CHEC-I(6)463> and reaction of the 5-methylthio derivative (137) (R = Ph) with hydrogen peroxide in acetic acid gives the sulfone (141) (R = Ph) (Equation (20)) (89MI 408-0l>. 

The sulfur in alkylthio groups of 1,2,4-thiadiazoles may be oxidized successively to the sulfoxide and sulfone stage. Thus, 5-amino(or anilino)-3-alkylthio- 1,2,4-thiadiazoles (321 R = NH2 or PhNH)85,133 and 3-alkylthio-1,2,4-thiadiazoles (321 R = H),90 on treatment with one or two moles of monoperphthalic acid, yield the appropriate oxidation products (322 and 323). Hydrogen peroxide or chlorine may replace the less convenient per-acid as the oxidizing reagent.86 By careful... 

Due to the low electron density at the carbon atoms in 1,3,4-thiadiazole, such reactions as nitration, sulfonation, acetylation, halogenation, etc. normally do not take place. However, 2-amino-substituted 1,3,4-thiadiazoles (73a-i) react with bromine in acetic acid to give the 5-bromo derivatives (74a-i). Similarly, the thiadiazolines (75b) and (75d-f) yield the corresponding 5-bromo derivatives (76b) and (76d-f). The thiadiazoline (75a), however,... 

Thiete structures have been suggested as fragmentation products in the mass spectra of a thietane fused to a 3-lactam, an ortho disulfide of a thiolbenzoate ester, -propanethiol, thiirane carboxylic acid esters, isothiazoles, thiazoles, 1,3-dithiole 2-thiones, 1,3-dithiolene-2-ones, S-ethyl thio-benzoate, and thianaphthene sulfones. Tetramethylthiete may have been formed on thermolysis of the p-toluenesulfonyl-hydrazone of 2,2,4,4-tetramethyl-3-thietanone. " Thiete 2-thione may be an intermediate in the decomposition of 1,2-ditholium salts by the action of bases. " 2,2-Diphenyl-2H-thiete is suggested as an intermediate in the reaction of diphenyldiazomethane with 1,2,3-benzo-thiadiazole which yields 9-phenylthioxanthene and three other products. ... 

Bis(4-aminophenoxy)benzophenone-3,3 -disulfonic acid, 496 4,4 -Bis(4-aminophenoxy)biphenyl, 461 4,4 -Bis-(p-aminophenoxy)diphenyl-1,3,4-thiadiazole, 307 Bis[4-(p-aminophenoxy)phenoxy]dimethylsilane, 479 2,2 -Bis[4-(4-amino-phenoxy) phenyl] hexafluoroisopropylidene, 477 1,3-Bis [5 -[3"-(p-aminophenoxy)-pheny 1]-oxadiazol-2-yl]benzene, 307 2,2 -Bis(4-(4-aminophenoxy)phenyl)propane, 477, 487 Bis(aminophenoxy phenyl)-sulfone, 489 B is [4-(3 -anrinophenoxy)phenyl] sulfone, 503 A,A -Bis(4-aminophenyl)-A, A -diphenyl-l,4-phenylenediamine, 468... 

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