1,2,5-Thiadiazole 1,1-dioxides synthesis

Another example of thiadiazole 1,1 -dioxide synthesis using sulfuryl chloride is the reaction with benzilbis(trimethylsilyl)imine, which has been reported to afford the 3,4-diphenyl derivative 97a (68LA174). 

A new method for the synthesis of 1,2,5-thiadiazoline 5,5-dioxides 231 was achieved by reacting activated aryl nucleophiles to the C=N double bond of the corresponding thiadiazoles 230 in the presence of AlClj as a catalyst at room temperature (00MI4). The yields of 4-aryl-derivatives ranged from 38 to 92%. 

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. 

Only two examples of the synthesis of pyrrolo[3,4-r-]pyridazines that begin with a pyridazine have been reported. The first involves a Diels-Alder reaction. Thus pyridazine 88 under thermal conditions provides the heterodiene 89 intermediate with loss of CO2, which is trapped / situ with A -phenyldiazamaleimide to form 90 in the yields shown (Scheme 8) <20010L3647>. Alternatively, the thiadiazole 1,1-dioxide 91 can produce 89 by loss of SO2. 

The synthesis and preliminary biological activity of substituted 7-alkylseleno-l,4-dihydro[l,6]naphthyridines have been reported <2000DOC218> along with their further synthetic ttansformations <2001RCB122>. There have also been reports of the preparation of selenium-containing fused heterocycles. The C=0 function in benzothiophen-3-ones, 3,4-dihydrothiopyrano[3,2-. ]benzothiophen-4(2//)-ones, and 3,4-dihydro-2//,5//-thiopyrano[2, 3 4,5]thiopyrano[3,2-/ ]ben-zothiophen-4-ones reacts with selenium dioxide and thionyl chloride to give fused 1,2,3-selena and thiadiazoles via their semicarbazones <1999IJB308>. 

The modified cephalosporin ceftobiprole (31-8), yet another compound that contains a double bond at the ring carbon, though in this case with a rather complex extended side chain, has shown activity in the clinic against some strains of multidrug resistant bacteria. The synthesis starts with the weU-precedented acylation of the cephalosporin (31-2), available in several steps from the commercially available 7-acetoxy cephalosporanic acid, with the activated thiadiazole carboxylic acid (31-1). The hydroxyl group in the product (31-3) is then oxidized with manganese dioxide to afford the corresponding aldehyde (31-4). This product is then condensed with the fcw-pyrrolidyl phosphonium salt (31-5), itself protected with the... 

In certain bicyclic and polycyclic thiadiazoles the ring can be hydrolytically cleaved to an o-diamine and sulfur dioxide. This process is a reversal of the reaction pathway involved in the synthesis of thiadiazoles from o -diamines and thionyl chloride or iV-sulfinylaniline under anhydrous conditions (see Section 4.26.5.1.1), and is analogous to, but much slower than, the hydrolysis of sulfurdiimides. In contrast to (1), which steam distilled without decomposition, steam distillation of [l,2,5]thiadiazolo[3,4-c][l,2,5]thiadiazole (21) produced only oxamide. Under milder conditions (75 °C, 12 h) a mixture of the diamine (22), oxamide and elemental sulfur was obtained (75JOC2749). Similar hydrolytic instability was observed in thiadiazole rings angularly joined to an anthraquinone (70RCR923) and ben-zofuroxan (78CPB3896). 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

Applications of Lalezari and Hurd-Mori reactions are also highlighted in the synthesis of a new class of 1,2,3-selenadiazoles 243 and 1,2,3-thiadiazoles 244 <07JHC1165>. Reaction of sulfonylacetate 241 with semicarbazide 237 gives semicarbazone 242, and oxidative cyclization of 242 with selenium dioxide in acetic acid at 60-70 °C furnishes selenadiazole 243. Compound 242 also undergoes Hurd-Mori reaction with excess thionyl chloride to give thiadiazole 244. 

D. Synthesis of 1,2,5-Thiadiazole-l,1-dioxides and Reduced Forms of 1,2,5-Thiadiazole. ... 

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... 

A unique thiadiazole synthesis from the industrial raw materials sulfur dioxide and potassium cyanide has been reported by Ross and... 

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). 

Most syntheses of the title compounds from nonheterocyclic materials use similar strategies, generally based on sulfamides or sulfuryl chloride reactivities. A classification of the known methods, according to the fragments used, is gathered below. Very few methods of synthesis of thiadiazole 1,1-dioxide derivatives from other heterocyclic compounds are known. 

A new synthesis of lH,3/f-2,l,3-benzothiadiazole-2,2-dioxide has been reported by Acheson and collaborators370. The reaction of N,N -dibenzyl-1,2-diaminobenzene (383) with thionyl chloride (equation 127) gives the l,3-dibenzyl-lH,3//-2,l,3-benzothiadiazole-2-oxide (384) which, on oxidation with m-chloroperbenzoic acid, yields the iV,iV -dibenzylated thiadiazole-2,2-dioxide (385). Debenzylation of 385 leads to the parent thiadiazole-2,2-dioxide (386), which heretofore was not readily synthesized. 

Hofmann s classical synthesis of 3,5-disubstituted 1,2,4-thiadiazoles by the oxidation of thioamides (1869)3 continues to be further exemplified. The oxidants employed include iodine,9-11 bromine,12 chlorine,13 and nitrous acid,14 as well as /V-chlorobenzamidine (which is recovered as benzamidine)15 and IV-sulfinyl-p-toluenesulfonamide (which evolves sulfur dioxide in the process).16 Irradiation with UV light in the presence of oxygen effects the same reaction, but has not been used on a preparative scale.17... 

Anil Kumar and coworkers have also reported the synthesis of IL-grafted sulfonyl hydrazine 87 and reacted with various ketones to afford the resxiltant IL-supported hydrazones (Scheme 10) [41]. IL-boxmd hydrazones were converted to 1,2,3-selenadiazoles 88 and 1,2,3-thiadiazoles 89 in the presence of selenixim dioxide and thionyl chloride, respectively. Present process provides access toward the library synthesis of 1,2,3-thiadiazoles and 1,2,3-selenadiazoles under mild reaction condition. 

The condensation of sulphamide and diethyl oxalate produces 3,4-dihydroxy-1,2,5-thiadiazole 1,1-dioxide as the dipotassium salt in high yield. The free acid (177) is an excellent precursor for the preparation of other functional derivatives, and for building up fused ring systems incorporating the 1,2,5-thiadiazole 1,1-dioxide structure (see below). The two isomeric benzothiadiazole acetoximes (178) and (179) undergo the Beckmann reaction, resulting in the fission of their carbocyclic ring. This provides an effective synthesis of novel ajS-unsaturated 1,2,5-thiadiazoles (180 X = COaH, Y = CR=CHCN X =... 

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