Convenient Preparations of 3,5-Disubstituted 1,2,4-Thiadiazoles by Oxidative Dimerization of Thioamides

Takikawa, Yuji; Shimada, Kazuaki; Sato, Katsuyuki; Sato, Shinichi; Takizawa, Saburo

doi:10.1246/bcsj.58.995

Cited by 53 publications

(17 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the appearance of this product was not predicted, chemical oxidation of thioamides is a known route to the synthesis of 3,5-disubstituted-1,2,4-thiadiazoles (39). The spontaneous dimerization of various thioamide S-oxides in the presence of acid or heat to form 3,5-disubstituted-1,2,4-thiadiazoles has been reported (9,12).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolism of Thioamides by Ralstonia pickettii TA

Dodge¹,

Richman

Johnson

et al. 2006

Appl Environ Microbiol

View full text Add to dashboard Cite

Information on bacterial thioamide metabolism has focused on transformation of the antituberculosis drug ethionamide and related compounds by Mycobacterium tuberculosis. To study this metabolism more generally, a bacterium that grew using thioacetamide as the sole nitrogen source was isolated via enrichment culture. The bacterium was identified as Ralstonia pickettii and designated strain TA. Cells grown on thioacetamide also transformed other thioamide compounds. Transformation of the thioamides tested was dependent on oxygen. During thioamide degradation, sulfur was detected in the medium at the oxidation level of sulfite, further suggesting an oxygenase mechanism. R. pickettii TA did not grow on thiobenzamide as a nitrogen source, but resting cells converted thiobenzamide to benzamide, with thiobenzamide S-oxide and benzonitrile detected as intermediates. Thioacetamide S-oxide was detected as an intermediate during thioacetamide degradation, but the only accumulating metabolite of thioacetamide was identified as 3,5-dimethyl-1,2,4-thiadiazole, a compound shown to derive from spontaneous reaction of thioacetamide and oxygenated thioacetamide species. This dead-end metabolite accounted for only ca. 12% of the metabolized thioacetamide. Neither acetonitrile nor acetamide was detected during thioacetamide degradation, but R. pickettii grew on both compounds as nitrogen and carbon sources. It is proposed that R. pickettii TA degrades thioamides via a mechanism involving consecutive oxygenations of the thioamide sulfur atom.Amide compounds are very common in biological systems, but thioamides are rare. Correspondingly, reports of amide metabolism are very common, whereas comparatively little has been reported on bacterial thioamide metabolism. Thioamides are found naturally in the copper-chelating compound methanobactin described in Methylosinus trichosporium OB3b (24). The antibiotic sulfinemycin, produced by Streptomyces albus NRRL 3384, has a primary thioamide S-oxide moiety (28). Thioacetamide has applications in leather, textile, paper, rubber, and petroleum industries (36), and 2,6-dichlorothiobenzamide (chlorthiamid) is used as a herbicide (20). Thioamide compounds such as 2-ethyl-4-pyridinecarbothioamide (ethionamide) are important second-line drugs in the treatment of multidrug-resistant Mycobacterium tuberculosis and M. leprae (34,35). In M. tuberculosis, oxidation of the thioamide sulfur is a necessary step in converting the prodrug ethionamide to its active form (5, 13).It is currently unclear how bacteria would metabolize thioamides in a manner that supports growth. There are two biochemically logical mechanisms by which thioamides could be metabolized to liberate ammonia and thus support growth as a nitrogen source. First, enzymes could directly hydrolyze the thioamide C-N bond. These reactions have been shown to be catalyzed by some peptidases, but thioamides are typically hydrolyzed slowly compared to structurally analogous amides (4,7,8,29). A second mechanism involves oxygenation of the sulfur ato...

show abstract

Section: Discussionmentioning

confidence: 99%

“…Synthesis and characterization of 3,5-dimethyl-1,2,4-thiadiazole has been described previously (39,44). For the present study, synthesis was based on a generalized protocol for 3,5-disubstituted 1,2,4-thiadiazoles (39). Acetyl chloride (2.5 ml) was added gradually over 4 min to 4.91 g of thioacetamide dissolved in 100 ml of DMSO.…”

Section: Methodsmentioning

confidence: 99%

Metabolism of Thioamides by Ralstonia pickettii TA

Dodge¹,

Richman

Johnson

et al. 2006

Appl Environ Microbiol

View full text Add to dashboard Cite

show abstract

“…The subsequent hydrolysis of F might lead to intermediacy, thioamide S-oxide G. Our previous findings showed that when thioamide S-oxide was treated with electrophilic reagents or Lewis acids, the corresponding 3,5-disubstituted 1,2,4-thiadiazole was efficiently afforded [33]. In the present case, it was assumed that the resulting thioamide S-oxides G might also cause self-condensation by contact with silica gel or p-toluenesulfonic acid to give 6.…”

Section: Amentioning

confidence: 99%

Novel conversion of 6H‐1,3,5‐oxathiazine S‐oxides into 5‐membered heterocyclic compounds

Rafiqul

Shimada

Aoyagi

et al. 2004

Heteroatom Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…Various types of oxidants have been employed for the C-S coupling of benzothioamide derivatives to the corresponding thiadiazoles such as halogens [4] [12], nitrous acid, [5] hydrogen peroxide, [6] thionyl chloride, [7] a mixture of HCl-dimethylsulfoxide (DMSO), [8] and pyridinium salt-DMSO. [9] Meanwhile, the reaction of 1-monosubstituted thioureas with bis(acyloxyiodo)arene derivatives has been utilized as a synthetic procedure to obtain 3,5-bis-(phenylamino)-1,2,4-thiadiazoles. [10] Thiadiazoles are interesting building blocks in medicinal chemistry [11][12][13] and industrial chemical [14] that are easy to access.…”

Section: Introductionmentioning

confidence: 99%