Properties of 1,2,5-Thiadiazoles

spectra of a series of 2-amino-l,3,4-thiadiazoles have been compared with those of the selena-analogues. The dependence of the chemical shifts of the NH protons on temperature and concentration reflects their participation in intermolecular hydrogen-bonding.  

The quaternization by methyl iodide of a series of 2-alkyl-5-methyl-1,3,4-thiadiazoles has been studied quantitatively by a spectrometric method. The product distribution due to quaternization at N-3 and N-4 in a series of 2,5-disubstituted 1,3,4-thiadiazoles has been determined. The observed influence of alkyl substituents on product distribution is almost the same as in comparable thiazoles, but is less pronounced than in the pyridazine series, probably owing to differences in the geometry of their respective transition states.  

Chanon, H. Lund, and J. Metzger, Tetrahedron Letters, 1972, 3857. H. Lund, Acta Chem. Scand., 1973, 27, 391. 

In the course of their work on meso-ionic five-membered heterocyclic systems, Grashey et ai described the production, by several routes, of 2-amino-1,3,4-thiadiazolium salts (115), and their ready conversion, by alkalis, into the meso-ionic l,2,4-triazole-3-thiones (116) (see also these Reports, Vol. 2, p. 746, ref. 105). It probably occurs by deprotonation of (115), attack by the nucleophile at position 5, followed by ring-cleavage and recyclization to (116). Transformations involving 2-mercapto-analogues 

While diaza-heteroaromatic compounds (e.g. pyrimidines, diazoles) can, in principle, form diquatemary salts without loss of aromaticity, the introduction of the second alkyl group is difficult, undoubtedly because of the reduction in nucleophilicity of the second ring-nitrogen resulting from the quatemization of the first. Diquatemary salts of thiadiazoles of type 

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Physical Properties of 1,2,3-Thiadiazoles. Lanthanide-induced shifts have been used for elucidation of the structure of thermally generated monoxides of 1,2,3-thiadiazoles ( H and C). A calculation has been developed for the evaluation of lanthanide-induced shifts according to the McConnell-Robertson equation. The o and Or parameters of triazoles were also determined by n.m.r. spectroscopy. ... 

Physical Properties of 1,2,4-Thiadiazoles. The X-ray determination of the 1 1 adduct between Hector s Base (274 R = H) and methyl isocyanate shows that it forms without a heterocyclic rearrangement the compound is a 5-(iV-methylthiocarbamoylimino)4-phenyl-3-phenylamino-4//-l,2,4-thia-diazoline [274 R = MeNHC(S)]... 

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). ... 

The remarkable pestiddal properties of 1,2,4-thiadiazole derivatives, especially of organophosphorus compounds, and of 5-ethoxy-3-trichloro-methyl-1,2,4-thiadiazole and its analogs are the subject of brief separate Sections. Screening programs and individual studies continue3 to reveal a variety of other biological activities of 1,2,4-thiadiazoles. 

Properties of 1,2,4-Thiadiazoles. Proton n.m.r. spectroscopy of the products of the condensation of 5-amino-3-methyl-1,2,4-thiadiazole with nitriles RCN shows that they consist of an equilibrium mixture of (213a) and (213b), which does not occur with the corresponding 1,2,4-oxadiazoles. The structure of the product (214 X = O) obtained by the reaction of Hector s Base (214 X = NH) with mineral acid has been elucidated by means of X-ray crystallography.An... 

In the field of thiadiazole chemistry the study of meso-ionic compounds stimulates interest (75, 98—113). The parent thiadiazoles have been obtained for the first time only in recent years they have now been joined by 1,3,4-selenadiazole (75, 120), whose physical properties have been compared with those of relevant analogues in studies of bonding in these systems. The nature of the products formed in the photolysis of 1,2,3-thiadiazoles is accounted for in terms of a transient thiocarbene intermediate (75, 10). 

Functionalization of Thiadiazole. Mesoionic compounds prepared on the 1,2,3-thiadiazolium scaffold have been studied for their chemical and biological properties and are known to display monoamine oxidase inhibitory activity. The reaction of 1,2,3-thiadiazole with /7-toluenesulfonic acid affords quantitative conversion to thiazolium /7-toluenesulfonate. The thiazolium tosylate can be reacted with sulfur in the presence of sodium hydride in DMF to afford the 5-thiolated mesoionic compound in 48% yield (eqs 1 and 2). ... 

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. ... 

The excellent pesticidal and fungicidal properties of 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole (363) are well known <82AHC(32)285). It is a commercial product and is marketed under a variety of names of which Terrazole is the most common. Since 1984, a variety of 1,2,4-thiadiazole derivatives have been found to possess fungicidal activity. Thus, compounds such as (364), (365), and (366) and... 

Azine approach. Diazotization of 2-amino-3-hydroxypyridines might be expected to yield the bicyclic ring system (631) by bond formation between the oxygen and the diazonium group in the first formed diazonium salt fused 1,2,3-thiadiazoles and -triazoles are formed by this type of reaction. Compounds prepared by this method, however, are highly unstable and have spectroscopic properties consistent with the pyridodiazooxide structure (630) (74CS(6)222>. 

Azole approach. 3,4-Diamino-l,2,5-thiadiazole reacts with 1,2-dicarbonyl compounds to form pyrazines (747) (76JHC13). From the reaction of 1,2,5-thiadiazole 1,1-oxides such as (748) with o-phenylenediamine, the l,3-dihydro[l,2,5]thiadiazolo[3,4-Z>]quinoxaline 2,2-dioxide (749) is formed. To understand this reaction it is pointed out that the 1,2,5-thiadiazole 1,1-dioxide ring is to be regarded as alicyclic rather than aromatic and is strongly 7r-electron deficient. Substituents with leaving properties in the 3,4-positions are therefore readily displaced as in the reaction of (748) (75JOC2743). 

P.A.Wandrey, "Some Explosive Properties of Substituted 1,2,3-thiadiazole Compounds", OECD-IGUS Literature Lists 183 (1979)... 

The 1,2,5-thiadiazole ring is susceptible to reductive cleavage by a number of reagents including zinc and mineral acids,sodium and alcohol,and Raney nickel. Reduction occurs at the N—S bond (also the site of cleavage of 1,2,3- and 1,2,4-thiadiazoles) with formation of hydrogen sulMe and regeneration of the NCCN portion of the molecule in a reduced form. This property has been employed as a method of structure proof of 1,2,5-thiadiazoles in a number of cases. 

Most activity in this area has centered around the isolation of so-called pseudo-bases (82) in which the cyano group is replaced by a hydroxy group. Thus the pseudo-base is obtained, in addition to the normal Reissert compound, from S-nitroisoquinoline, " 3-methyl-5-nitroisoquinoline, 6-nitroquinoline, and phthalazine. Heating the pseudo-bases in alcohol gives rise to the ethers 83. A discussion of some of the chemistry and properties of the pseudo-bases has appeared. The formation of the pseudo-bases can be suppressed and that of the Reissert compounds increased by the use of a phase-transfer catalyst. Pseudo-bases have also been obtained in attempts to form Reissert compounds from 1,6-naphthyridine and 4,6-phenanthroline. 2-Phenyl-1,2,3-thiadiazole and benzoyl chloride in the presence of cyanide gave 84 and imidazo[l,5-a]pyrazines with acid chloride gave 85 in reactions analogous to the pseudo-base formation. 

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-... 

In 1975, Russo reported that when N,N -diphenylbenzidine or N,N -diphenyl-l,4-phenylene diamine were interfacially polymerized with a mixture of 1,2,5-thiadiazole and 3,4-furan dicarbonyl chloride, co-polyamides were obtained having good heat resistance, dielectric properties, and mechanical properties, "comparable to those of other construction materials."... 

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, ... 

The 1,2,4-thiadiazole moiety has been incorporated in (3-lactam antibacterials to modulate pharmacokinetic properties and more recently into a cephalosporin. The cephalosporin 129 displays a good balance of serum stability and in vitro activity. The cephalosporin derivative 48 (see Section 5.08.7.4) also shows good pharmacokinetic properties <2001JAN364>. 

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