1,3,4-Thiadiazolium salts synthesis

The oxidative cyclization of thioacylamidines 83 is one of the best methods for the synthesis of unsymmetrical 3,5-diaryl- or dialkyl-1,2,4-thiadiazoles 84 (Equation 23) <2004HOU277>. Typical oxidants used in the cyclization step include bromine, iodine, or nitric acid, and, more recently, hydrogen peroxide in the presence of perchloric acid has been used. N-Substituted thioacylamidines give rise to 1,2,4-thiadiazolium salts <1997JOC3480>. 

A variation using thioacylguanidines affords 5-substituted-3-amino-l,2,4-thiadiazoles. If an amidinothiourea is oxidized, 5-amino-l,2,4-thiadiazoles are obtained. A recent example of this type of synthesis has been reported the amidinothiourea 87 was oxidized to the 1,2,4-thiadiazolium salt 88 on treatment with bromine (Equation 25) <2003SC2053>. 

A short synthesis of imidazoles 47 was discovered on the basis of the reaction of 3,5-diaryl-l,2,4-dithiazolium triiodides 46 (X = I3) with glycinates or aminoacetonitrile. Intermediate (thiocarbonyl)amidines 48 were oxidized in situ to 1,2,4-thiadiazolium salts 49 by the triiodide anion resulting in imidazoles 47. The same reaction with 3,5-diaryl-l,2,4-dithiazolium perchlorates 46 (X = C104) stops at the formation of amidines 48 due to the lack of an oxidizing counterion (Scheme 3) <1997JOC3480>. 

Hafner s synthesis of azulene, the cyclopentadienyl anion can also be used to introduce the five-membered fragment. This anion reacts with heterocyclic quaternary salts in a complex manner the pseudoazulene, however, is obtained in one step. The total yields are only about 10%, but it is possible to use starting materials that are easily available in large quantities. This variant was applied to prepare 2f/-cyclopenta[d]pyridazines (56) using thiadiazolium salts " and cyclopenta[c ]thiopyranes (31) using N-methyl thiazoliumbromide. °... 

A novel, one pot ring transformation / desulphurisation of substituted 1,2,4-thiadiazolium salts (86), which provides a versatile synthesis of imidazoles has been reported by Liebscher and Rolfs. Thus, the thiadiazolium salts (86) which were prepared by oxidation of A-(thiocarbonyl)-A -methylamidines (85), underwent smooth conversion into imidazoles (87) under the previous oxidative conditions <97JOC3480>. 

The 1,3-dipolar cycloaddition of 2-diazopropane with diarylideneacetones is temperature dependent, leading to mono-, di-, and tri-substitution products. The 1,3-dipolar cycloaddition of diazomethane and diazoacetate with 5-sulfur-2(5//)furanones provides a synthesis of furoisoxazolines. The 1,3-dipolar cycloaddition of 1-aza-2-azoniaallene cations with isothiocyanates produces 1,3,4-thiadiazolium salts and 1,2,4-thazolium salts. 

Aromatic thioamides react with MeC(0)CHClC(0)C02Et to give a 3 1 ratio of ethyl 5-acetyl-2-aryl-thiazole-4-carboxylates and the isomeric products (2). Modifications of the Hantzsch synthesis continue to appear. Thus, 2-aryl-5-aroyl-thiazoles may be prepared from the JV -thioaroyl-iViV-dimethyl-formamidines ArC(S)N=CHNMea and a-bromo-ketones [strictly speaking, this is a Type F (C—N—C—S + C) synthesis], whilst 5-amino-2-phenyl-l,2,3-thiadiazolium salts [e.g. (3)] and compounds with the general structure RCHgCN (e.g. R = CN or COaEt) yield 4-amino-thiazoles. ... 

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