1,3,4-Thiadiazolium salts

Thus quaternized thiazoles (170) consume two equivalents of OH on titration because the pseudo bases (171) ring open to (172), which form anions (173). Quaternized oxazoles (174) are readily attacked by hydroxide to give open-chain products such as (175) (74AHC(17)99), and quaternized 1,3,4-oxadiazoles behave similarly. Quaternary isothiazoles (e.g. 176) are cleaved by hydroxide (72AHC(l4)l), as are 1,2,4-thiadiazolium salts (177 178). 

A considerable extension of that method was reached by the condensation of 1,2- and 1,3-dithiolium- 1,3-thiaselenium- and 1,2,4-thiadiazolium salts with pyrroles, 2- or 4-phenyl- 2,4-diphenyl- and 4,5-diphenyl imidazoles (70TL481). At room temperature and in acetonitrile solution some of... 

The benzyl 1,2,4-thiadiazolium salt 59 can be isomerized to the 5-imino-l,2,4-thiadiazolidine 60 when treated with a strong base like potassium /-butoxide (Equation 17) <1997ZOR1728>. If the 2-substituent is replaced with a tosylmethyl group and the 5-position substituent is a diphenylamino in place of an aniline such as compound 61, then a rearrangement occurs to give an imidazole 62 (Equation 18) <1997ZOR1728>. 

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>. 

The desilylation of 3,5-diaryl-1,2,4-thiadiazolium salts 740 with CsF results in ring expansion to afford substituted 2/7-1,3,5-thiadiazines 741 in moderate yield (Scheme 319) <1999J(P1)1709, CHEC-III(9.09.10.2)514>. 

A novel ring transformation/desulfurization of substituted 2-methyl-l,2,4-thiadiazolium salts 1481 provides a versatile entry to imidazoles 1482 with a variety of substituents. The starting 1,2,4-thiadiazolium salts 1481 can be prepared from A -(thiocarbonyl)-A -methylamidines 1480 under mild oxidative conditions. Related salts, 1,2,4-dithiazolium triiodides 1483, also react with amines to form imidazoles 1484 <1997JOC3480>. Alternatively, A -(thiocarbonyl)-A -methylamidines 1485 can be transformed into 1-substituted imidazoles 1487 via A-methylation followed by elimination of methylthiol (Scheme 383) <1997JOC3480>. 

Trisubstituted imidazoles are accessible via desulfurization / ring transformation of substituted 2-methyl-1,2,4-thiadiazolium salts <97JOC3480>. 

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>. 

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