Acetanilide, deacetylation

The role of deacetylation in methemoglobinemia induced by acetanilide (4.101) and phenacetin (4.107) has been demonstrated. Indeed, concomitant i.p. administration of BNPP considerably reduced the hematotoxicity of these compounds [87]. Recent studies have shown that /V-hydroxyphenetidine (4.144), a metabolite of deacetylated phenacetin, is responsible for hemolysis and methemoglobin formation [88]. 

Sulfoxide Reduction. Reduction of the sulfoxide of the mercapturic acid of 2-chloro-f+-isopropylacetanilide by Intestinal microflora has been shown in vitFo (9), but has not been demonstrated to occur in tissues. The excretion of this mercapturate sulfoxide, which is excreted into the intestine with the bile, in feces from germfree rats dosed with the acetanilide is vivo evidence for the reductive function of the intestinal microflora (49) in MftP catabolism. This reduction, in addition to deacetylation, is another source for cysteine conjugates which can be translocated to the tissues for metabolism or excretion, or remain in the intestine and further catabolized by the microflora. 

In 2015, Liu and coworkers reported the formal synthesis of tipifarnib, a farne-syltransferase inhibitor, by using a palladium-catalyzed C-H alkenylation as a key step (Scheme 16.35) [71]. Aniline derivative 160 reacted with AC2O to form an acetanilide intermediate, followed by ort/zo-palladation under the influence of a palladium catalyst to produce compound 162. Oxidative Heck reaction with 161 and cyclization/deacetylation then occurred to afford quinolinone 163 in 95% yield in one pot. This quinolinone was then converted to tipifarnib by the reported procedure [72]. 

Diarylamines. A mixture of 3,5-dichlorobromobenzene, acetanilide, Gu-powder, and K-carbonate heated 30 hrs. at 180-200° with stirring, and the product refluxed 15 hrs. with KOH in alcohol-water 3,5-dichlorodiphenylamine. Y 76.5%. F. e., deacetylation also with HGl, s. J. Hebky, O. Badek, and J. Kejha, Goll. 24, 3988 (1959). 

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