View source for Pyrazolone

{{Short description|Chemical compound}}
'''Pyrazolone''' is 5-membered [[heterocycle]] containing two adjacent [[nitrogen]] atoms. It can be viewed as a derivative of [[pyrazole]] possessing an additional [[ketone|carbonyl]] (C=O) group.  Compounds containing this functional group are useful commercially in [[Analgesic|analgesics]] and dyes.<ref name=KO>{{cite book |doi=10.1002/0471238961.1625180111151814.a01|chapter=Pyrazoles, Pyrazolines, and Pyrazolones|title=Kirk-Othmer Encyclopedia of Chemical Technology|year=2000|last1=Kornis|first1=Gabe I.|isbn=0471238961}}</ref>

==Structure and synthesis==
Pyrazolone can exist in two isomers: 3-pyrazolone and 4-pyrazolone. 
<div class="skin-invert-image">{{multiple image
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 | image1=1,2-Dihydro-3H-pyrazol-3-one Structural Formula V1.svg
 | image2=4H-Pyrazol-4-one Structural Formula V1.svg
 | footer = Chemical structures of 3-pyrazolone (left) and 4-pyrazolone (right)
}}</div>{{clear-left}}

These isomers can interconvert via lactam–lactim and imine–enamine [[tautomerism]]; these conversion often display [[photochromism]].  For pyrazolone derivatives, the 3-pyrazolone isomer can be stabilized with ''N''-alkyl or ''N''-aryl substituents.

:[[File:Lactam-Lactim-Tautomerie Pyrazolone.svg|class=skin-invert-image|left|400px|frameless]]{{clear-left}}

The first synthesis of pyrazolones was  reported in 1883 by [[Ludwig Knorr]], via a condensation reaction between [[ethyl acetoacetate]] and [[phenylhydrazine]].<ref>{{cite journal|last1=Knorr|first1=Ludwig|title=Einwirkung von Acetessigester auf Phenylhydrazin|journal=Berichte der Deutschen Chemischen Gesellschaft|date=July 1883|volume=16|issue=2|pages=2597–2599|doi=10.1002/cber.188301602194|language=German|url=https://zenodo.org/record/1425305}}</ref>
:[[File:KnorrPrep.png|class=skin-invert-image|left|420px|frameless]]{{clear-left}}
Many pyrazolones are produced by functionalization of preformed pyrazolones.

==Applications==
===Pharmaceuticals===
{{missing information|section|safety profile of analgesics (which ones are withdrawn and whether there is a common theme in adverse effects)|date=August 2022}}
[[File:Phenazone2DCSD.svg|class=skin-invert-image|thumb|200px|right|[[Antipyrine]] (phenazone), the earliest pyrazolone based drug]]

Pyrazolones are amongst the oldest synthetic pharmaceuticals, starting with the introduction of [[antipyrine]] (phenazone) in 1880s.<ref name=pharma1>{{cite journal|last1=Brogden|first1=Rex N.|s2cid=2761563|title=Pyrazolone Derivatives|journal=Drugs|date=1986|volume=32|issue=Supplement 4|pages=60–70|doi=10.2165/00003495-198600324-00006|pmid=3552586}}</ref><ref>{{cite journal|last1=Brune|first1=Kay|title=The early history of non-opioid analgesics|journal=Acute Pain|date=December 1997|volume=1|issue=1|pages=33–40|doi=10.1016/S1366-0071(97)80033-2}}</ref> The compounds generally act as [[analgesics]] and include [[dipyrone]] (Metamizole), [[aminophenazone]], [[ampyrone]], [[famprofazone]], [[morazone]], [[nifenazone]], [[piperylon]] and [[propyphenazone]]. Of these [[dipyrone]] is perhaps the most widely used.<ref name=pharma1 /><ref name=Zhao>{{cite journal |doi=10.1016/j.ejmech.2019.111893|title=Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect|year=2020|last1=Zhao|first1=Zefeng|last2=Dai|first2=Xufen|last3=Li|first3=Chenyang|last4=Wang|first4=Xiao|last5=Tian|first5=Jiale|last6=Feng|first6=Ying|last7=Xie|first7=Jing|last8=Ma|first8=Cong|last9=Nie|first9=Zhuang|last10=Fan|first10=Peinan|last11=Qian|first11=Mingcheng|last12=He|first12=Xirui|last13=Wu|first13=Shaoping|last14=Zhang|first14=Yongmin|last15=Zheng|first15=Xiaohui|journal=European Journal of Medicinal Chemistry|volume=186|page=111893|pmid=31761383|pmc=7115706}}</ref>  

The basic structure has been also used in a number of newer drugs of other effects.<ref name=Zhao/> [[Edaravone]] is useful for prevention and/or therapy of arterial wall injury.<ref>{{cite journal |doi=10.1016/j.bmc.2020.115463|title=Chemical reactivity and uses of 1-phenyl-3-methyl-5-pyrazolone (PMP), also known as edaravone|year=2020|last1=Bailly|first1=Christian|last2=Hecquet|first2=Paul-Emile|last3=Kouach|first3=Mostafa|last4=Thuru|first4=Xavier|last5=Goossens|first5=Jean-François|journal=Bioorganic & Medicinal Chemistry|volume=28|issue=10|page=115463|pmid=32241621|s2cid=214766793 }}</ref>  [[Eltrombopag]] is used to address low blood platelet count.

===Dyes===
Pyrazolone groups are present in several important dyes. They are commonly used in combination with [[azo group]]s to give a sub-family of azo dyes; sometimes referred to as azopyrazolones ([[tartrazine]], [[orange B]], [[mordant red 19]], [[yellow 2G]]).  [[Acid Yellow 17]], [[Acid Yellow 23]] (tartrazine), [[Pigment Yellow 13]], and [[Pigment Red 38]] are produced on the multi-ton scale annually.<ref name=KO/>

===Ligands===
Pyrazolones have been studied as ligands.<ref>{{cite journal|last1=CASAS|first1=J|last2=GARCIATASENDE|first2=M|last3=SANCHEZ|first3=A|last4=SORDO|first4=J|last5=TOUCEDA|first5=A|title=Coordination modes of 5-pyrazolones: A solid-state overview|journal=Coordination Chemistry Reviews|date=June 2007|volume=251|issue=11–12|pages=1561–1589|doi=10.1016/j.ccr.2007.02.010}}</ref>

==References==
{{reflist}}

==External links==
* {{MeshName|Pyrazolones}}
* [https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=351317 Pubchem - 3-Pyrazolone]
* [https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=19753145 Pubchem - 4-Pyrazolone]

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[[Category:Pyrazolones| ]]