1.2.4- Thiadiazoles chemical properties

The chemistry of analogues and various derivatives of the compounds discussed is quite a rich field. Thiazoles, methylthiazoles, thiadiazoles, and benzothiazoles have been studied theoretically. The agreement of theoretical indices with the course of substitution reactions and some physico-chemical properties is satisfactory (1,2-thiazole,51 1,3-thiazole,52-56 thiadiazoles,56 benzo-l,3-thiazole53,54). 

No naturally occurring 1,2,4-thiadiazole having been reported so far, all compounds are of synthetic origin. The parent of the series, 1,2,4-thiadiazole, was first synthesized in 1955s by the sequence of reactions 8->9—>-10->-2,B 6 but remains relatively inaccessible. Because of its sensitivity it is not a practicable starting material for the preparation of derivatives these are therefore always built up directly by suitable cyclization reactions and subsequent modification of the substituentB as required. This section is confined to direct syntheses the numerous interconversions that furnish additional derivatives from the preformed 1,2,4-thiadiazole nucleus are considered with the chemical properties of the individual classes of compounds. 

Although 3,4-dichloro-l,2,5-thiadiazole-l,1-dioxide (76) is related structurally to 3,4-dichlorothiophene-1,1-dioxide their chemical properties are quite different. The thiophene compound is a reactive diene and readily dimerizes via an auto Diels-Alder reaction. Furthermore, its chlorine atoms are unreactive toward weak nucleophilic reagents like water and alcohol. The thiadiazole compound, on the other hand, shows no tendency to dimerize and is highly reactive toward water and alcohol. 

Chemical Properties of 1,3,4-Thiadiazoles. Thermal decomposition of cis-(288) proceeds at 50°C to give ( , -Bu C=NN=CHBu, but decomposition of fra s-(288) proceeds only at 145 C, giving (jE )-Bu HC=NNHCOBu and SO, which disproportionates to S and SO2. Several reactions of substituted 2-mercaptothiazoles with chloroacetamides, chlorodiaminotriazines, and ethyl bromoacetate-hydrazine-substituted benzaldehydes, and of 2,5-... 

Chemical Properties of 1,2,5-Thiadiazoles. Lithiation and carbonylation of one methyl of 3,4-dimethyl-1,2,5-thiadiazole were described, followed by subsequent transformation into alcohol, mesylate, and vinyl derivatives. The reaction of 2,5-dicyclohexyl-l,2,5-thiadiazole-3,4-dione with RC6H4-SO2N3 gave the compounds (294 R = 4-MeO or 3-O2N). ... 

Chemical Properties. - Cyclocondensation of 4-amino-1,2,3-thiadi-azoles with R1COCHR2COR3 gave 1,2,3-thiadiazolof3,4-aJpyrimidinium salts [317 R,R1, R2,R3 = mix of H,Me,Ph (for R2-R1< only)] in 17-7 yield333. 5-Amino-1,2,3-thiadiazole is converted to the Na or Ba salt of (318) with aqueous NaOH 1 or Ba(0H)2 8H2033, respectively. 5-Azido-4-carbethoxy-1,2,3-thiadiazole could not be prepared from NaN3 and the 5-chloro analogue the diazo compound (319) was isolated in 73 yield. Confirmation for (319) was derived from its spectral data and its thermolysis to ethyl a-... 

Chemical Properties. - 5-Acetonyl-1,2,4-thiadiazoles have been prepared from the corresponding 5-chloro compounds by treatment with fcBu acetoacetate3 1. 2-(1,2,4-Thiadiazol-5-yl)vinyl phos-... 

Chemical Properties. - 3>4-Dimethyl-1,2,5-thiadiazole reacts with benzyne to give (346),(347), MeCN and Sg. Similar results were obtained for the Se analogue, but yields were very low (1-2 ) . Unsymmetrical diamines (348) can be formed from 3,4-dimethoxy-1,2,5-thiadiazole 1-oxide by reaction with ArNH2 then NH. ... 

Thiadiazoles 195 Synthesis 195 Physical properties 196 Chemical properties 196... 

Chemical Properties.—5-Substituted 3-amino-l,2,4-thiadiazoles are very weak bases [pA"a = 0,8 0,3 for (45 R = Et)] aqueous solutions of their hydrochlorides are strongly acidic. On being acylated or sulphenylated, they yield mono-(46 X = Ac or o-NOaCeH4S) or di-acylamino-derivatives... 

Chemical Properties.—Complete sets of harmonic symmetry force constants have been calculated for 1,3,4-thiadiazole, based on observed vibrational... 

Pesin and his group have continued their investigation of benzo-2,1,3-thiadiazoles and have provided a summary of their recent work. In their opinion, the quinoid structure of benzo-2,1,3-thiadiazole and its selenium analogue is excluded by the sum of their physical and chemical properties, especially i.r. spectra. However, their preferred heteroaromatic structure... 

Similar effects, although with rather subtle differences, are also observed in the furazan and thiadiazole pyrimidine derivatives (91) and (92). These two molecules have quite different chemical properties, as evidenced both by the extremely facile nucleophilic substitution of the amino-group in (91), which is less easy in (92), and also by the ready photoaddition to the... 

Oxadiazoles resemble in their chemical properties the corresponding 1,2,4-thiadiazoles (discussed in detail on p. 256) [462]. 

Chemical Properties.—Photolytic Reactions. The mechanism of the photolysis of 1,2,3-thiadiazole involves the intermediate formation of the thioketen (20) and thiiren (19), which decompose to the observed photoproducts, carbon disulphide, and ethynethiol (18), respectively. The growth rates of bands of comparable intensity in the i.r. spectra of (20) and (18) indicate that these species are increasing at a similar rate. The photolysis of 4- and 5-deuteriothiadiazole was similarly studied. ... 

Chemical Properties.—Alkylation. Treatment of 3,5-diethoxy-l,2,4-thiadiazole (67) with benzyl bromide in boiling acetonitrile ( Hilbert-Johnson reaction ) slowly yields a monoalkylation product (68). Chloromethyl benzyl ether effects the alkylation rapidly in good yield. The use of ribosyl halides should make novel nucleosides accessible. ... 

Chemical Properties.—Alkylation. Methylation of 2-amino-5-benzoyl-l,3,4-thiadiazole and its derivatives has been systematically examined. The direction of methylation, which occurs at the N-3 atom of the ring and the exocyclic amino-group, is influenced by the structure of the substrate, the nature of the reagent (Mel, Me2S04, or CH2N2), and the reaction conditions. 2-(Substituted amino)-l,3,4-thiadiazoline-5-thiones (104) are 5-methylated to (105) by one equivalent of methyl iodide, in the presence or absence of alkali. Further methylation occurs at N-3 or N-4, but may lead to mixtures, the composition of which depends on the ratio of the reactants and on the degree of substitution of the 2-amino-group in (105). At 190 C, (105 R = R = Me) isomerizes to (106) ... 

Chemical Properties.—The rates of quaternization of 1,2,5-thiadiazole, 2,1,3-benzothiadiazole, and the corresponding selenium heterocycle have been examined by a competition method, using dimethyl sulphate in sulpholane, ... 

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