Editing Paracetamol (section)

==Chemistry==

===Synthesis===

====Classical methods====
The classical methods for the production of paracetamol involve the [[acetylation]] of [[4-aminophenol]] with [[acetic anhydride]] as the last step. They differ in how 4-aminophenol is prepared. In one method, [[nitration]] of [[phenol]] with [[nitric acid]] affords [[4-nitrophenol]], which is reduced to 4-aminophenol by [[hydrogenation]] over [[Raney nickel]]. In another method, [[nitrobenzene]] is reduced [[electrolysis|electrolytically]] giving 4-aminophenol directly. Additionally, 4-nitrophenol can be selectively reduced by [[Tin(II) chloride|Tin(II) Chloride]] in [[absolute ethanol]] or [[ethyl acetate]] to produce a 91% yield of 4-aminophenol.<ref name = Ullmann/><ref>{{cite web |url=https://patents.google.com/patent/US2998450A/en |title=US Patent 2998450 |date= |website= |publisher= |access-date= |quote= |archive-date=14 April 2021 |archive-url=https://web.archive.org/web/20210414033102/https://patents.google.com/patent/US2998450A/en |url-status=live }}</ref><ref>{{cite journal |vauthors = Bellamy FD, Ou K |date= January 1984 |title=Selective reduction of aromatic nitro compounds with stannous chloride in non acidic and non aqueous medium |journal=Tetrahedron Letters |volume=25 |issue=8 |pages=839–842 |doi=10.1016/S0040-4039(01)80041-1 |doi-access =  |title-link = doi }}</ref>
[[Image: Classic syntheses of paracetamol.png|class=skin-invert-image|thumb|center|upright=2|Classical methods for the production of paracetamol]]

====Celanese synthesis====
An alternative industrial synthesis developed at [[Celanese]] involves firstly direct acylation of phenol with acetic anhydride in the presence of [[hydrogen fluoride]] to a ketone, then the conversion of the ketone with [[hydroxylamine]] to a [[ketoxime]], and finally the acid-catalyzed [[Beckmann rearrangement]] of the cetoxime to the para-acetylaminophenol product.<ref name = Ullmann>{{Ullmann |title = Analgesics and Antipyretics |vauthors = Friderichs E, Christoph T, Buschmann H |doi = 10.1002/14356007.a02_269.pub2 |date=15 July 2007 |isbn=3-527-30673-0}}</ref><ref>{{cite patent |country = US |number = 4524217 |status = patent |title = Process for producing N-acyl-hydroxy aromatic amines |pubdate = 18 June 1985 |inventor = Davenport KG, Hilton CB |assign1 = Celanese Corporation}}</ref>

[[File: Celanese method for the preparation of paracetamol.png|class=skin-invert-image|thumb|center|upright=2|Celanese method for the preparation of paracetamol]]

===Reactions===

[[File:Парацетамол 9.jpg|thumb|right|Paracetamol crystals (crystallized from an aqueous solution) under a microscope]]
''4''-Aminophenol may be obtained by the amide [[hydrolysis]] of paracetamol. This reaction is also used to determine paracetamol in urine samples: After hydrolysis with hydrochloric acid, ''4''-aminophenol reacts in ammonia solution with a phenol derivate, e.g. salicylic acid, to form an [[indophenol]] dye under oxidization by air.<ref>{{cite journal| vauthors = Novotny PE, Elser RC| title = Indophenol method for acetaminophen in serum examined| journal = [[Clin. Chem.]]| volume = 30| issue = 6| pages = 884–6| year = 1984| doi = 10.1093/clinchem/30.6.884| pmid = 6723045| doi-access = free |title-link = doi }}</ref>