Thioacetamide S-oxidation

The nature of thioamide-iS-oxides and their role in the formation of 1,2,4-thiadiazoles have recently been studied in detail by Walter and his co-workers.27,29-32 Treatment of thioacetamide at —30 to —10° with perhydrol saturated with ammonium sulfate furnishes a 58% yield of crystalline thioacetamide-S-oxide, which if pure may be kept almost indefinitely at 0°.29 Thioformamide-iS-oxide, the parent compound of this series, is even more stable than the methyl homolog.81 The reaction between thioacetamide-nS-oxide and thioacetamide proceeds less readily than that involving the aromatic analogs in dilute sulfuric acid at room temperature, N-acetylthioacetamide (6%) is... 

Thioacetamide acts as an indirect hepatotoxin and causes parenchymal cell necrosis. It can be metabolized in vivo to acetamide, which itself is carcinogenic. Acetamide is then hydrolyzed to acetate. Thioacetamide-induced liver necrosis has been explained by a scheme that includes the metabolic conversion of thioacetamide to its S-oxide, followed by the further metabolism of thioacetamide S-oxide to a reactive intermediate that can either bind to liver macromolecules or be further degraded to acetamide and polar products. Examples of thioacetamide s... 

Low et al. (2004) have proposed a model to explain thioacetamide-induced hepatotox-icity and cirrhosis in rat livers. The pathways of thioacetamide-induced liver fibrosis were found to be initiated by thioacetamide S-oxide derived from the biotransformation of thioacetamide by the microsomal flavin-adenine nucleotide containing monooxygenase and cytochrome P450 systems and involve oxidative stress and depletion of succinyl-CoA, thus affecting heme and iron metabolism. Karabay et al. (2005) observed such hepatic damage in rats with elevation of total nitrite level in livers and decrease in arginase activity. The authors have reported that nitrosative stress was essentially the critical factor in thioacetamide-induced hepatic failure in rats. 

HgS passed into an aq. soln. of thioacetamide S-oxide until a red color test with ferric chloride is negative thioacetamide. Y 87%. W. Walter, A. 633, 35 (1960). 

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