Thiadi azoles

In 1955, Hurd and Mori first described the preparation of 1,2,3-thiadiazole as an unexpected product from the reaction of the hydrazone 5 and thionyl chloride. The authors were attempting to prepare the six membered anhydride 7 in an analogous manner to the 5-membered anhydride 9, prepared from 8 using thionyl chloride. However, when the hydrazone 5 and thionyl chloride were mixed and heated at 60°C for 1 hour followed by cooling, the thiadiazole acid 6 precipitated out and was isolated by filtration. This serendipitous discovery led to a significant advance in the synthesis of thiadi azoles. 

The structure of the intermediate obtained from 3-phenyl-5-amino-l,2,4-thiadi-azole (Goerdeler and Deselaers, 1958) was elucidated by UV- and IR-spectroscopy. The results are consistent with the nitrosoamine structure 3.18. Its UV spectrum (Fig. 3.4) is very similar to that of the A-methyl-TV-nitroso compound 3.19, but different from that of the isomeric compound 3.20 with a methyl group in the 4-position (Goerdeler and Deselaers, 1958). The spectrum of this 4-methyl derivative is expected to be similar to that of the nitrosoamine structure 3.21, which is obviously not present, at least not in detectable tautomeric equilibrium concentration. 

The oxidation of A-alkoxythiocarbonylamidines 121 is a good method for the preparation of 5-alkoxy-l,2,4-thiadi-azoles 122, and this is a variation of a type C synthesis (see Section 5.08.9.4) (Equation 32) <1996GHEC-II(4)307>. 

Instead of the corresponding cyclized product, only the N-(, 2,4-thiadi-azol-3-yl)aminomethylenemalonate (1133) was obtained in 12% yield from the reaction of 3-amino-5-ethoxycarbonylamino-l,2,4-thiadiazole and EMME in polyphosphoric acid at 110°C for 3 hr (77JHC621). 

The product Ci4Hn,N4S, obtained from the meso-ionic 1,3,4-thiadi-azole-2-thione (251, R = R = Ph) and dimethylazodicarboxylate was initially regarded as the six-membered meso-ionic heterocycle 259. However, subsequent studies have established that the product is, in fact, 2-phenyl-5-phenylazo-l,3,4-thiadiazole (260). ... 

When N-substituted pyrrole 37 and trithiazyl trichloride (NSCfis are heated at reflux in carbon tetrachloride, IH-pyrrolo[2,3-r 4,5-. V-Substituted pyrrolo[2,3-f]-l,2,5-thiadi-azole 38 is believed to be an intermediate in this reaction (Equation 2). The enamine character of the carbon-carbon double bond of 38 is presumed to be enhanced compared to pyrrole 37, rendering 38 more reactive toward (NSCfis. 

Nitram ino-1 3,4-thiadi ozol e, C3 H4N403 S, crysts, mp 177°. Was prepd by nitrating with coned HNOs the 2-amino-l,3,4-thiadi-azole dissolved in coned HaS04... 

Mercapto-thiadi azole Butanedioldiglycidylether No charge effect... 

Pyrido[2.3-d]pyrimidin 4-Hydroxy-2-mercapto- E9c, 136 (4-COOR — 2-(=N — COOR) -[Pg.354]

Thiazolidinediones are another class of heterocyclic carboxylic acid surrogates commonly used for peroxisome proliferator-activated receptors (PPAR) agonists, as potent antihyperglycemic and lipid activity modulators. Other interesting, but less studied heterocyclic surrogates are 3,5-dioxo-l,2,4-oxadiazohdine, 3-hydroxy-1,2,5-thiadiazoles, l,2,4-oxadiazole-5(4//)-ones, 1,2,4-thiadi-azole-5(4H)-ones , 3,5-difluoro-4-hydroxyphenyl, and 3 -hydroxy-7-pyrones. ... 

---