1.3.4- Thiadiazoles, substituted

The synthesis of numerous thiadiazoles substituted in the 5-position with carbamoyl or heteroaryl moieties and hydroxyl or amino groups in the 2-position (Scheme 20), was achieved by reacting dithioesters with semicarbazide or thiosemicarbazide and cyclizing the resulting acylated sem-... 

Ring protons of 1,2,3-thiadiazoles are known to undergo rapid deuterium exchange under basic conditions (74AHC(16)l). Practically, this led to the conversion of 4-substituted thiadiazoles into thioethers and thiafulvenes (Scheme 4) (68CJC2251,68CJC1057). Thiadiazoles substituted in the 5-position can be deprotonated and then alkylated (equation 17) (68CJC1057). 

Substituted-1,3,4-thiadiazol-2-yl)-4-quinazolones 2-Amino-5-(l-iftethyl-2-nitro-5-imidazolyl)-1,3,4-thiadiazole 2-Anilino-5-(amino-oxy)methyl-l,3,4-thiadiazole Substituted 2-acylamino-1,3>4-thiadiazoles l,3,4-Thiadiazol-2-yl- -mercaptocinnamamides N-(2-Anilino-l,3,4-thiadiazol-S-ylmethoxy)phthalimide N -(l,3,4-Thiadiazol-2-yl)-N -benzylidenesulphanUainides 2-p -AminobenzenesuIphonamido-S-ethyl 1,3,4-... 

Curing Systems. The most commonly used vulcanizing agent for the polyethers not containing AGE, that is, ECH and ECH—EO, is 2-mercaptoimidazoline, also called ethylenethiourea [96-45-7]. Other commercially appHed curing agents include derivatives of 2,5-dimercapto-l,3,4-thiadiazole, trithiocyanuric acid and derivatives, bisphenols, diamines, and other substituted thioureas. 

For both azole and benzazole rings the introduction of further heteroatoms into the ring affects the ease of quaternization. In series with the same number and orientation of heteroatoms, rate constants increase in the order X = 0requires stronger reagents and conditions methyl fluorosulfonate is sometimes used (78AHC(22)71). The 1-or 2-substituted 1,2,3-triazoles are difficult to alkylate, but methyl fluorosulfonate succeeds (7IACS2087). 

Thiadiazoles are quaternized to give 3- or mixtures of 2- and 3-alkyl quaternary salts. In 5-amino-1,2,4-thiadiazole, quaternization takes place at the 4-position (90) (64AHC(3il). 1-Substituted 1,2,4-triazoles are quaternized in the 4-position (91), and 4-substituted 1.2,4-triazoles are quaternized in the 1- or the 2-position (92) 64AHC(3)l). 

Attempted diazotization in dilute acid sometimes yields primary nitroso compounds. Reactions of 3- and 5-amino-1,2,4-thiadiazoles with sodium nitrite and acid give primary nitrosamines (e.g. 432->433) (65AHC(5)n9) which can be related to the secondary nitrosamines (434) prepared in the normal way. 1-Substituted 5-aminotetrazoles with nitrous acid give stable primary nitrosamines (435). Primary nitrosamines have been isolated in the imidazole series. 

Acetanilides, benzoyl-colour couplers in colour photography, 1, 372 Acetanilides, pivaloyl-colour couplers in colour photography, 1, 372 Acetazolamide — see l,3,4-Thiadiazole-2-sulfonamide, 5-acetamido-Acetic acid, acetamidocyano-ethyl ester, 1, 307 Acetic acid, 2-acylphenyl-isochroman-3-one synthesis from, 3, 858 Acetic acid, 3-benzo[6]thiophenyl-biological activity, 4, 912 Acetic acid, l,2-benzoxazol-3-yl-electrophilic substitution, 6, 48... 

A reliable calculation of polarizabilities requires an adequate description of the outer part of the electron density. For this reason Kassimi and Lin [98JPC(A)9906] used augmented basis sets of triple- quality to study polarizabilities and dipole moments of thiazoles and thiadiazoles. They expect their results to be reliable within 5%. In addition, the authors provide MP2/6-31G geometries for most of their structures. Hyperpolarizabilities for substituted thiazoles obtained from calculations at lower levels are also provided [99MI2]. 

When 7r-deficient thiadiazoles are fused to an azine, electrophilic substitution is possible only in the presence of strongly electron-donating substituents (74BCJ2813) (Scheme 56). Some [l,3,4]thiadiazolo[3,2-a]pyrimidin-5-ones were brominated next to the oxo group (90DOK743). 

A rearrangement involving a fluctuating 1,2,3-thiadiazole ring has been found by Haddock et al. (1970) after diazotization of 7-amino-6-substituted 1,2,3-benzothia-diazoles (Scheme 6-46). 

A range of 4-substituted l,3-dithiole-2-thiones (71) and 2,6-substituted 1,4-dithiafulvalenes (73) were synthesised from 4-substimted 1,2,3-thiadiazoles (72). Reaction of (72) with NaH in a mixture of CS2 and acetonitrile led to the formation of (71), whereas absence of CS2 gave fulvalenes (73). This route was found to be very efficient for the preparation of 4-formyl-1,3-dithiole-2-thione (71 R = CHO), which was previously difficult to prepare, and thus allowed the synthesis of the novel 2,6(7)-bisformyltetraAiafulvalene (74) <96T3171>. 

Thiadiazoles have proven of some utility as aromatic nuclei for medicinal agents. For example, the previous volume detailed the preparation of a series of "azolamide" diuretic agents based on this class of heterocycle. It is thus of note that the 1,2,5-thiadiazole ring provides the nucleus for a clinically useful agent for treatment of hypertension which operates by an entirely different mechanism, p-adrenergic blockade. In its preparation, reaction of the amide-nitrile 211 with sulfur monochloride leads directly to the substituted thiadiazole 212. ... 

They have been several recent investigations of the reactions of disulfur dichloride with other organic substrates. Rokach and co-workers37 have found that 2-aminoacetamides afford 2-substituted l,2,5-thiadiazol-3(2J7)-ones (33). This illustrates a frequent facet of such reactions the elision of the second sulfur atom. A similar reaction, with loss of a sulfur atom, occurs with 2-alkylaminophenyl acetamides.38... 

Thiadiazoles (57) are produced by the reaction of fV-substituted hydrazones (58 R1, R2 = alkyl, aryl, H R3 = acetyl, ester, tosylate, etc.) with thionyl chloride.67... 

An ab initio theoretical study was conducted on 1,2,5-oxadiazole and 3-phenyl-l,2,5-oxadiazole to determine the molecular structures of these heterocyclic compounds. The rotational energy barrier between Ph ring and diazole nucleus was also evaluated. No considerable change of bond lengths inside the diazole nucleus was observed in the Ph-substituted heterocyclic compounds as compared to the oxadiazole and thiadiazole alone <2001MI215>. 

The thermally induced rearrangements in the furoxan series have also been found. In particular, the transformation of 3-R-substituted 4-(3-ethoxycarbonylthioureido)-l,2,5-oxadiazole 2-oxides into derivatives of 5-amino-3-(a-nitroalkyl)-l,2,4-thiadiazole and into (5-amino-l,2,4-thiadiazol-3-yl)nitroformaldehyde arylhydrazones has been reported (Equation 8) <2003MC188>. 

The X-ray structure for the 4-substituted 1,2,3-thiadiazole 11 has been published <2003JHC929>, and the values obtained for bond lengths and angles are in close agreement with those obtained for 4-phenyl-l,2,3-thiadiazole 10. 

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