1.2.3- Thiadiazole-4-carboxylic acid/ester

Condensations of 5-methyl-substituted 1,2,4-thiadiazoles with aromatic aldehydes lead to 5-styrylthiadiazoles. With carboxylic acid esters, ethoxalyl derivatives are formed, and isoamyl nitrite produces the corresponding oximes <1982AHC285>. These reactions are restricted exclusively to the 5-methyl-substituted 1,2,4-thiadiazoles reflecting the greater reactivity of substituents in the 5-position compared to the 3-position in 1,2,4-thiadiazoles. 

Condensation of the 5-methyl group in (80) (R = Me, Et, Ph, SMe) with aromatic aldehydes leads to 5-styrylthiadiazoles (79). The action of carboxylic acid esters gives ethoxalyl derivatives (81) and that of isoamyl nitrite produces the oxime (82) (Scheme 20) <82AHC(32)285>. These reactions are restricted exclusively to the 5-methyl group in (80) (R = Me), reflecting the greater reactivity of substituents in the 5-position compared to the 3-position in 1,2,4-thiadiazoles. This point is further illustrated when (80) (R = Me) is selectively converted into the carboxylic acid (83) on treatment with n-butyllithium and carbon dioxide (Scheme 20) <84CHEC-I(6)463). 

Thiete structures have been suggested as fragmentation products in the mass spectra of a thietane fused to a 3-lactam, an ortho disulfide of a thiolbenzoate ester, -propanethiol, thiirane carboxylic acid esters, isothiazoles, thiazoles, 1,3-dithiole 2-thiones, 1,3-dithiolene-2-ones, S-ethyl thio-benzoate, and thianaphthene sulfones. Tetramethylthiete may have been formed on thermolysis of the p-toluenesulfonyl-hydrazone of 2,2,4,4-tetramethyl-3-thietanone. " Thiete 2-thione may be an intermediate in the decomposition of 1,2-ditholium salts by the action of bases. " 2,2-Diphenyl-2H-thiete is suggested as an intermediate in the reaction of diphenyldiazomethane with 1,2,3-benzo-thiadiazole which yields 9-phenylthioxanthene and three other products. ... 

Attempted hydrolysis of the ester group in the thienothiadiazine 66 using H2SO4 and AcOH at 100 °C gave a moderate yield of the ring-contracted thieno[2,3-carboxylic acid. Compound 67 was... 

SN/N Imidazo[2,l- ][l,3,4]thiadiazole 135 <2004S1067> (Figure 20), 136 and 137 (Table 44) <2004BMC5651> 6-aryl-2-aryloxymethylimidazo[2,l- ][l,3,4]thiadiazoles 120 (Table 45) <2005SC2881> NN/N 4-methyl-3-phenyl-2-phenylcarbamoyloxy-37/,47/-imidazo[l,2- ][l,2,4]triazole-3a-carboxylic acid ethyl ester 125 and 4,3a-dimethyl-3-phenyl-2-phenylcarbamoyloxy-37/,4/7-imidazo[l,2- ][l,2,4]triazole-6-carboxylic acid methyl ester 126 (Table 46) <2001JOC8528>. 

K. Other 1,2,4-Thiadiazole Derivatives 1. Carboxylic Acids and Esters... 

Alkylthio-l,3,4-thiadiazoles from dithiocarbazic acid esters and carboxylic acid dilorides... 

The reaction of Tentagel-bound carboxylic esters with amidooximes has been used to prepare oxadiazoles (Entry 11, Table 15.20). Thiadiazoles have been prepared from support-bound iV-sulfonylhydrazones by treatment with thionyl chloride. Thiadiazole formation and cleavage from the support occurred simultaneously (Entry 12, Table 15.20). Perhydro-l-thia-2,5-diazole-2,2-dioxides (sulfahydantoins) have been prepared by aminosulfonylation of amino acids esterified with Wang resin, followed by ring-closure with simultaneous cleavage from the support [257]. 

By contrast, solvolysis of (109) in absolute ethanol produces dicyanoethylenes (112) as the primary products. The phenyl derivative (112 R = Ph) is too insoluble to react with hot 95% ethanol but the methyl derivative (113) yields a 1 1 mixture of nitrile (114) and ester (116), presumably via acylnitrile (115), in about 90% yield as indicated in Scheme 50. The carboxylate esters (110) are readily saponified to the acids (117) which readily undergo decarboxylation at 100 °C to produce 3-substituted 1,2,4-thiadiazoles (118) in good yields (Scheme 51) (74JOC962). 

---