Acetanilide

Acetanilide can be produced by reacting acetic anhydride with aniline:

:C₆H₅NH₂ + (CH₃CO)₂O → C₆H₅NHCOCH₃ + CH₃COOH

The preparation used to be a traditional experiment in introductory organic chemistry lab classes,See, e.g., {{citation | title = The preparation of acetanilide from aniline | url = http://wwwchem.uwimona.edu.jm/lab_manuals/c10expt23.html | publisher = Department of Chemistry, University of the West Indies at Mona, Jamaica | access-date = 2009-08-26}}; {{citation | first1 = Wilkins | last2 = Lowe | first2 = Valerie C. | title = Preparation of Acetanilide from Nitrobenzene | journal = J. Chem. Educ. | volume = 56 | issue = 7 | pages = 488 | year = 1979 | doi = 10.1021/ed056p488 | last1 = Reeve| bibcode = 1979JChEd..56..488R }}: the latter preparation includes the reduction of nitrobenzene to aniline. but it has now been widely replaced by the preparation of either paracetamol or aspirin, both of which teach the same practical techniques (especially recrystallization of the product) but which avoid the use of aniline, a suspected carcinogen.

Acetanilide is slightly soluble in water, and stable under most conditions. Pure crystals are plate shaped and appear colorless, white, or in between.

Acetanilide is used as an inhibitor of hydrogen peroxide decomposition and is used to stabilize cellulose ester varnishes. It has also found uses in the intermediation in rubber accelerator synthesis, dyes and dye intermediate synthesis, and camphor synthesis.{{Cite web |last=PubChem |title=Acetanilide |url=https://pubchem.ncbi.nlm.nih.gov/compound/904 |access-date=2022-12-10 |website=pubchem.ncbi.nlm.nih.gov |language=en}} Acetanilide is used for the production of 4-acetamidobenzenesulfonyl chloride, a key intermediate for the manufacture of the sulfa drugs.{{cite book | title = Ashford's Dictionary of Industrial Chemicals | edition = Third | year = 2011 | page = 33}}

In the 19th century acetanilide was one of a large number of compounds used as experimental photographic developers.

During the same period of time, acetanilide was introduced into medical practice as a fever-reducing agent under the name Antifebrin.{{cite journal |last1=Cahn |first1=A. |last2=Hepp |first2=P. |year=1886 |title=Das Antifebrin, ein neues Fiebermittel |journal=Centralbl. Klin. Med.}} 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.{{cite journal |last1=Brodie |first1=B. B. |last2=Axelrod |first2=J. |year=1948 |title=The fate of acetanilide in man |journal=Journal of Pharmacology and Experimental Therapeutics |volume=94 |issue=1 |pages=29–38}}

Acetanilide derived herbicides have been used since the 1960s or earlier. These include alachlor, metolachlor and xylachlor.OWEN, M. D. K. (1982). A Comparison Of The Herbicidal Activity Of Several Chloroacetamides And Their Effects On Protein Synthesis In Carrot And Soybean Cell Suspension Cultures (Order No. 8218534). Available from ProQuest Dissertations & Theses Global. (303227220). Retrieved from https://www.proquest.com/dissertations-theses/comparison-herbicidal-activity-several/docview/303227220/se-2

Acetanilide was the first aniline derivative found to possess analgesic as well as antipyretic properties, and was quickly introduced into medical practice under the names of Antifebrin by A. Cahn and P. Hepp in 1886.{{citation | last1 = Cahn | first1 = A. | last2 = Hepp | first2 = P. | title = Das Antifebrin, ein neues Fiebermittel | journal = Centralbl. Klin. Med. | year = 1886 | volume = 7 | pages = 561–64}}. But its (apparent) unacceptable toxic effects, the most alarming being cyanosis due to methemoglobinemia and ultimately liver and kidney damage,{{citation | last1 = Brodie | first1 = B. B. | last2 = Axelrod | first2 = J. | author-link2 = Julius Axelrod | title = The estimation of acetanilide and its metabolic products, aniline, N-acetyl p-aminophenol and p-aminophenol (free and total conjugated) in biological fluids and tissues | journal = J. Pharmacol. Exp. Ther. | year = 1948 | volume = 94 | issue = 1 | pages = 22–28 | pmid = 18885610}}. prompted the search for supposedly less toxic aniline derivatives such as phenacetin.{{citation | last1 = Bertolini | first1 = A. | last2 = Ferrari | first2 = A. | last3 = Ottani | first3 = A. | last4 = Guerzoni | first4 = S. | last5 = Tacchi | first5 = R. | last6 = Leone | first6 = S. | title = Paracetamol: new vistas of an old drug | journal = CNS Drug Reviews | year = 2006 | volume = 12 | issue = 3–4 | pages = 250–75 | pmid = 17227290 | doi = 10.1111/j.1527-3458.2006.00250.x| pmc = 6506194 }}. After several conflicting results over the ensuing fifty years, it was established in 1948 that acetanilide was mostly metabolized to paracetamol (acetaminophen) in the human body, and that it was this metabolite that was responsible for the analgesic and antipyretic properties.Multiple sources:

• {{citation |last1=Lester |first1=D. |title=Metabolic fate of acetanilide and other aniline derivatives. II. Major metabolites of acetanilide in the blood |journal=J. Pharmacol. Exp. Ther. |volume=90 |issue=1 |pages=68–75 |year=1947 |pmid=20241897 |last2=Greenberg |first2=L. A.}}.
• {{citation |last1=Brodie |first1=B. B. |title=The fate of acetanilide in man |journal=J. Pharmacol. Exp. Ther. |volume=94 |issue=1 |pages=29–38 |year=1948 |url=http://profiles.nlm.nih.gov/HH/A/A/A/D/_/hhaaad.pdf |pmid=18885611 |last2=Axelrod |first2=J. |author-link2=Julius Axelrod}}
• {{citation |last1=Flinn |first1=Frederick B. |title=The effect on the pain threshold of N-acetyl p-aminophenol, a product derived in the body from acetanilide |journal=J. Pharmacol. Exp. Ther. |volume=94 |issue=1 |pages=76–77 |year=1948 |pmid=18885618 |last2=Brodie |first2=Bernard B.}}.
• Cahn, A., & Hepp, P. (1886). Das Antifebrin, ein neues Fiebermittel. Centralbl. Klin. Med.
• Brodie, B. B., & Axelrod, J. (1948). The fate of acetanilide in man. Journal of Pharmacology and Experimental Therapeutics, 94(1), 29–38. The observed methemoglobinemia after acetanilide administration was ascribed to the small proportion of acetanilide that is hydrolyzed to aniline in the body.

• Nitroacetanilide

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{{cite AV media|url=https://www.youtube.com/watch?v=eQNLmkj_GBo|date=May 21, 2017|title="Making an old pain and fever medication" by NileRed|website=YouTube|people=NileRed}}

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Category:Photographic chemicals

Category:Withdrawn drugs