3- 1,2,5-thiadiazole 5,5-dioxide formation

The thermolysis of o-azidosulfonyl-f-anilines resulted in nitrene formation and trapping of the nitrene by the adjacent amino nitrogen to give a zwitterionic thiadiazole dioxide 108 from the dimethyl- or 6-membered heterocyclic ring precursor. The ring-opened/dealkylated derivative 109 was formed from other dialkyl or ring systems (Scheme 36) [74 JCS(P1)2451]. The pyrrolidino azide was unique in giving no thiadiazole, but rather products derived from a sulfonylnitrene precursor, perhaps in... 

The Hurd-Mori reaction,where a tosylhydrazone is converted by thionyl chloride to the corresponding thiadiazole, involves the formation of a 1,2,3-thiadiazole-3,3-dioxide. In one example, this type of compound was isolated and subsequently deoxygenated with thiourea <1991PS175>. There have been no further reports of S-linked sulfoxide or sulfone derivatives of 1,2,3-thiadiazoles since the publication of CHEC-II(1996). 

A formally antiaromatic 1,4-dihydropyrazinothiadiazole has been prepared and characterized by single crystal X-ray spectroscopy. The antiaromatic character of which has been supported computationally using NICS measurements <20070L1073>. CHIH-DFT computational studies on acenaphtho[l,2-f]-l,2,5-thiadiazole 1,1-dioxide led to simulations of its infrared (IR) and ultraviolate (LJV) spectra, the dipole moment and polarizability <2007JMT373>. 4,6-Dinitrobenzothiadiazole was determined to have an electrophilic reactivity of —8.40 which corresponds to a pK z° of 7.86 for Meisenheimer complexation with water and is close to the demarcation boundary (E = —8.5) between super-and normal-electrophiles and between reactive dienophiles and inert partners in Diels-Alder adduct formation <20070BC1744>. 

One procedure for the synthesis of these title ring systems appeared recently <2003S1079>. Yadav and Kapoor described that the transformation of some oxadiazole and thiadiazole derivatives bearing specially substituted methylsulfinyl side chain 131, when reacted with thionyl chloride, give ring-closed compounds 134. The reaction was carried out in pyridine under reflux conditions in 74-79% yield. As shown in Scheme 25, the authors assume that the first step is the formation of the sulfonium salt 132 which undergoes cyclization with hydrogen chloride and sulfur dioxide elimination to 133 and, finally, demethylation of this intermediate leads to the final product 134. 

The syntheses from [4+1] atom fragments, in which the Group 16 heteroatom is introduced between two nitrogen atoms, are the most widely applicable and versatile methods available for construction of the 1,2,5-thiadiazole ring system. These methods have been applied to the synthesis of monocyclic and polycyclic aromatic forms of these ring systems in addition to the direct formation of 1-oxides and 1,1-dioxides, 2-oxides, quaternary salts, and reduced forms. The earliest use of the [4+ 1] synthesis dates back to 1889 when Hinsburg prepared 2,1,3-benzothiadiazole (I) from o-phenylenediamine and sodium bisulfite. 

Due to the absorption of UV radiation by the reactant nucleophiles and the solvent in the zone of interest, application of classical spectrophotometric methods to follow the mechanism of formation of imidazo[4,5-f]-[l,2,5]thiadiazoles 51 from reaction of the parent thiadiazoles 1,1-dioxides 89 and ureas/thioureas was restricted. Consequently, details of the mechanism and equilibrium constants were established by CV <2004JP01091, 2003JP0220>. It was found that the reaction proceeded by a stepwise mechanism with an intramolecular second step as outlined in Scheme 4. In solution, this reaction was reversible, and the equilibrium could be shifted to the side of the reactants by a temperature increase. For example, a 3.54mM solution of 51b in DMF, with a 0.1 M NaC104 as supporting electrolyte, presented a featureless CV between 0.9 and —2.8 V which corroborated with the... 

The reaction of Tentagel-bound carboxylic esters with amidooximes has been used to prepare oxadiazoles (Entry 11, Table 15.20). Thiadiazoles have been prepared from support-bound iV-sulfonylhydrazones by treatment with thionyl chloride. Thiadiazole formation and cleavage from the support occurred simultaneously (Entry 12, Table 15.20). Perhydro-l-thia-2,5-diazole-2,2-dioxides (sulfahydantoins) have been prepared by aminosulfonylation of amino acids esterified with Wang resin, followed by ring-closure with simultaneous cleavage from the support [257]. 

The synthesis of 1,2,5-thiadiazoles from a-diamines was studied as early as 1897 when Michaelis attempted the preparation of the parent compound by reaction of ethylenediamine with sulfur dioxide. The product, however, was bissulfimic acid (28) which readily lost sulfur dioxide to form the betaine (28a). Later Shew reported that 3,4-dicyano-l,2,5-thiadiazole (30) results from the reaction of cis-diaminomaleonitrile (29, HCN tetramer) with thionyl chloride, a reaction which is analogous to 2,1,3-benzothiadiazole formation from o-phenylenediamines. The synthesis of the parent 1,2,5-thiadiazole and some alkyl analogs (32) was accomplished by reaction of salts of... 

The direct formation of disubstituted l,2,5-thiadiazole-l,l-dioxides (57) by condensation of a-diketones with sulfamide was reported by Wright and by Vorreither and Ziegler. The 1,2,5-thiadiazoline-1,1-dioxides (58) were prepared by a similar method employing a-hydroxy ketones. Hydrogenation of both 57 and 58 over Adams catalyst provided the corresponding disubstituted 1,2,5-thiadiazolidine-1,1 -dioxides (60). 2-Alkyl-l, 2,5-thiadiazoline-l, 1-... 

Phenyl-l,3,4-oxathiazol-2-one (370), prepared from primary amides and tri-chloromethanesulfenyl chloride, undergoes a ready thermal elimination of carbon dioxide with the formation of the nitrile sulfide ylide (371). This can be trapped by a wide variety of unsaturated dipolarophiles, and with an alkyne provides a ready route to isothiazoles (372) (see Chapter 4.17). Applications to 1,2,4-thiadiazole synthesis are described in Chapter 4.25. Thermolysis of l,3,4-oxadiazolin-5-ones (500 C/10 mmHg) results in the loss of CO2 and generation of the corresponding nitrilimine (78JOC2037). 

It has been found that some sulfonamides act as carbonic anhydrase (an enzyme that catalyzes the reaction between C02 and water with the formation of H+ and HC03"). The first compound prepared was acetazolamide (2-acetamido-1,3,4-thiadiazole-5-sulfonamide) 48, which increases the urine volume after administration184,185. Other agents like hydrochlorothiazide (6-chloro-3,4-dihydro-2i7-l,2,4-benzothiazine-7-sulfonamide-1,1-dioxide) 49 were developed later and are more effective. They inhibit... 

I = TS with 1,3-thiazole 1,1-dioxide II = TS with 1,3,4-thiadiazole 1,1-dioxide a = for addition of acetylene b = for addition of ethylene c = for exo addition of cyclopropene d = for endo addition of cyclopropene HOF = heat of formation computed by AMI E = total energy (a.u.) computed with B3LYP/6-3lG(d)/AMl AEi = activation barrier (kcal/mol) computed by AMI AEn = activation barrier (kcal/mol) computed with B3LYP/6-3lG(d)/AMl. 

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