Acetanilide is theorganic compound with the formulaC6H5NHC(O)CH3. It is the N-acetylated derivative ofaniline.[7] It is an odourlesssolid chemical of leaf or flake-like appearance. It is also known asN-phenylacetamide,acetanil, oracetanilid, and was formerly known by thetrade nameAntifebrin.
The preparation used to be a traditional experiment in introductory organic chemistry lab classes,[8] but it has now been widely replaced by the preparation of eitherparacetamol oraspirin, both of which teach the same practical techniques (especiallyrecrystallization of the product) but which avoid the use of aniline, a suspectedcarcinogen.
Acetanilide is slightly soluble in water, and stable under most conditions.[5] Pure crystals are plate shaped and appear colorless, white, or in between.
Acetanilide is used as aninhibitor ofhydrogen peroxide decomposition and is used to stabilizecelluloseester varnishes.[7] It has also found uses in the intermediation inrubber accelerator synthesis, dyes and dye intermediate synthesis, andcamphor synthesis.[9] Acetanilide is used for the production of 4-acetamidobenzenesulfonyl chloride, a key intermediate for the manufacture of thesulfa drugs.[10]
In the 19th century acetanilide was one of a large number of compounds used as experimentalphotographic developers.
During the same period of time, acetanilide was introduced into medical practice as a fever-reducing agent under the name Antifebrin.[11] It was one of the first aniline derivatives found to possess analgesic and antipyretic properties. However, its use was later discontinued due to toxic side effects, including methemoglobinemia, which led to cyanosis.[12]
Acetanilide was the first aniline derivative found to possessanalgesic as well asantipyretic properties, and was quickly introduced into medical practice under the names of Antifebrin by A. Cahn and P. Hepp in 1886.[11] But its (apparent) unacceptable toxic effects, the most alarming beingcyanosis due tomethemoglobinemia and ultimately liver and kidney damage,[14] prompted the search for supposedly less toxic aniline derivatives such asphenacetin.[15] After several conflicting results over the ensuing fifty years, it was established in 1948 that acetanilide was mostlymetabolized to paracetamol (acetaminophen) in the human body, and that it was this metabolite that was responsible for the analgesic and antipyretic properties.[16][12][17][11] The observed methemoglobinemia after acetanilide administration was ascribed to the small proportion of acetanilide that ishydrolyzed to aniline in the body.
^ab"Front Matter".Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge:The Royal Society of Chemistry. 2014. p. 846.doi:10.1039/9781849733069-FP001.ISBN978-0-85404-182-4.N-Phenyl derivatives of primary amides are called 'anilides' and may be named using the term 'anilide' in place of 'amide' in systematic or retained names of amides. (…) However, names expressingN-substitution by a phenyl group on an amide are preferred IUPAC names.
^See, e.g.,The preparation of acetanilide from aniline, Department of Chemistry, University of the West Indies at Mona, Jamaica, retrieved2009-08-26;Reeve, Wilkins; Lowe, Valerie C. (1979), "Preparation of Acetanilide from Nitrobenzene",J. Chem. Educ.,56 (7): 488,Bibcode:1979JChEd..56..488R,doi:10.1021/ed056p488: the latter preparation includes the reduction of nitrobenzene to aniline.
^Brodie, B. B.;Axelrod, J. (1948), "The estimation of acetanilide and its metabolic products, aniline,N-acetylp-aminophenol andp-aminophenol (free and total conjugated) in biological fluids and tissues",J. Pharmacol. Exp. Ther.,94 (1):22–28,PMID18885610.
^Lester, D.; Greenberg, L. A. (1947), "Metabolic fate of acetanilide and other aniline derivatives. II. Major metabolites of acetanilide in the blood",J. Pharmacol. Exp. Ther.,90 (1):68–75,PMID20241897.
^Flinn, Frederick B.; Brodie, Bernard B. (1948), "The effect on the pain threshold ofN-acetylp-aminophenol, a product derived in the body from acetanilide",J. Pharmacol. Exp. Ther.,94 (1):76–77,PMID18885618.
