View source for Reimer–Tiemann reaction

{{Short description|Chemical reaction for ortho-formylation of phenols}}
{{Reactionbox
| Name = Reimer–Tiemann reaction also known as RT reaction
| NamedAfter = Karl Reimer <br/> [[Ferdinand Tiemann]]
| Type = Substitution reaction
| Section3 = {{Reactionbox Identifiers
 | RSC_ontology_id = 0000072
 }}
}}

The '''Reimer–Tiemann reaction''' is a [[chemical reaction]] used for the ''[[Arene substitution pattern|ortho]]''-[[Formylation reaction|formylation]] of [[phenols]].<ref name=March>{{JerryMarch|page=726-7}}</ref> 
<ref name="2005Review">{{Cite book|last1=Wynberg and Meijer, Egbert|title=The Reimer–Tiemann Reaction|year=2005|page=14|doi=10.1002/0471264180.or028.01|first1=Hans|last2=Meijer|first2=Egbert W.|isbn=9780471264187}}</ref><ref>{{cite book|title=Organic Reactions, Volume 28|last=Dauben, William G.|publisher=Wiley-Interscience|year=1982|isbn=978-0471861416|location=Hoboken, NJ|pages=1–36|doi=10.1002/0471264180.or028.01|chapter = The Reimer-Tiemann Reaction}}</ref><ref>{{Citation |last=Wynberg |first=Hans |title=3.4 - The Reimer–Tiemann Reaction |date=1991-01-01 |url=https://www.sciencedirect.com/science/article/pii/B9780080523491000482 |work=Comprehensive Organic Synthesis |pages=769–775 |editor-last=Trost |editor-first=Barry M. |place=Oxford |publisher=Pergamon |language=en |doi=10.1016/b978-0-08-052349-1.00048-2 |isbn=978-0-08-052349-1 |access-date=2022-02-28 |editor2-last=Fleming |editor2-first=Ian|url-access=subscription }}</ref> with the simplest example being the conversion of [[phenol]] to [[salicylaldehyde]]. The reaction was first reported by [[Karl Reimer]] and [[Ferdinand Tiemann]].<ref name = R-T/>

[[File:Reimer-Tiemann Reaction Scheme.png|center|300px|The Reimer-Tiemann reaction]]

==Reaction mechanism==
[[File:Reimer-Tiemann_Reaction_Mechanism.png|thumb|right|350px|The mechanism of the Reimer-Tiemann reaction]]
[[Chloroform]] ('''1''') is deprotonated by a strong base (normally [[hydroxide]]) to form the chloroform carbanion ('''2''') which will quickly alpha-eliminate to give [[dichlorocarbene]] ('''3'''); this is the principal reactive species. The hydroxide will also deprotonate the phenol ('''4''') to give a negatively charged phenoxide ('''5'''). The negative charge is delocalised into the aromatic ring, making it far more nucleophilic. Nucleophilic attack on the dichlorocarbene gives an intermediate dichloromethyl substituted phenol ('''7'''). After basic hydrolysis, the desired product ('''9''') is formed.<ref>{{cite journal|last1=Hine|first1=Jack|last2=Van Der Veen|first2=James M.|title=The Mechanism of the Reimer-Tiemann Reaction|journal=Journal of the American Chemical Society|date=December 1959|volume=81|issue=24|pages=6446–6449|doi=10.1021/ja01533a028|bibcode=1959JAChS..81.6446H }}</ref>

===Selectivity===
By virtue of its two [[electron-withdrawing group|electron-withdrawing]] chlorine groups, the carbene ('''3''') is highly electron deficient and is attracted to the electron rich phenoxide ('''5'''). This interaction favors selective ''ortho''-formylation, consistent with other [[electrophilic aromatic substitution]] reactions.

==Reaction conditions==
Hydroxides are not readily soluble in chloroform, thus the reaction is generally carried out in a [[Multiphasic liquid|biphasic]] solvent system. In the simplest sense this consists of an aqueous hydroxide solution and an organic phase containing the chloroform. Therefore, the two reagents are separated and must be brought together for the reaction to take place. This can be achieved by rapid mixing, [[phase-transfer catalyst]]s, or an [[emulsion|emulsifying]] agent such as [[1,4-dioxane]] as solvent.

The reaction typically needs to be heated to initiate the process; however, once started, the Reimer–Tiemann Reaction can be highly exothermic. This combination of properties makes it prone to [[thermal runaway]]s.

==Scope==
The Reimer–Tiemann reaction is effective for other hydroxy-aromatic compounds, such as [[naphthol]]s.<ref>{{cite journal|last1=Russell|first1=Alfred|last2=Lockhart|first2=Luther B.|title=2-HYDROXY-1-NAPHTHALDEHYDE|journal=Organic Syntheses|date=1942|volume=22|pages=63|doi=10.15227/orgsyn.022.0063}}</ref> Electron rich heterocycles such as [[pyrroles]] and [[indoles]] are also known to react.

Dichlorocarbenes can react with alkenes and amines to form dichlorocyclopropanes and [[isocyanide]]s respectively. As such the Reimer–Tiemann reaction may be unsuitable for substrates bearing these functional groups. In addition, many compounds can not withstand being heated with hydroxide.

==Comparison to other methods==
The direct [[formylation reaction|formylation]] of aromatic [[chemical compound|compounds]] can be accomplished by various methods such as the [[Gattermann reaction]], [[Gattermann–Koch reaction]], [[Vilsmeier–Haack reaction]], or [[Duff reaction]]; however, in terms of ease and safety of operations, the Reimer–Tiemann reaction is often the most advantageous route chosen in chemical synthesis. Of the reactions mentioned before, the Reimer–Tiemann reaction is the only route not requiring [[acidic]] and/or [[anhydrous]] conditions.<ref name=2005Review /> Additionally the Gattermann—Koch  reaction is not applicable to phenol [[Substrate (chemistry)|substrates]].

==Variations==
Using [[carbon tetrachloride]] instead of chloroform gives a [[carboxylic acid]] product instead of an aldehyde.<ref>{{cite journal|last1=Gaonkar|first1=A.V.|last2=Kirtany|first2=J.K.|title=ChemInform Abstract: Reimer-Tiemann Reaction Using Carbon Tetrachloride|journal=ChemInform|date=2010|volume=22|issue=41|page=1991|doi=10.1002/chin.199141092}}</ref> For example, this reaction variant with phenol would yield [[salicylic acid]].

==Historical references==
Reimer and Tiemann published several papers on the subject.<ref name=Reimer>{{cite journal|last1=Reimer|first1=K.|title=Ueber eine neue Bildungsweise aromatischer Aldehyde|journal=Berichte der Deutschen Chemischen Gesellschaft|date=1876|volume=9|pages=423–424|url=https://babel.hathitrust.org/cgi/pt?id=hvd.cl1hyz;view=1up;seq=469|trans-title=On a new way of forming aromatic aldehydes|language=de|doi=10.1002/cber.187600901134}}</ref><ref>Reimer, Karl (1883) [[:File:A.W.v. Hofmann Nachruf 1883 auf K. Reimer.pdf|"Sitzung vom 22. Januar 1883"]]. ''Berichte der deutschen chemischen Gesellschaft''. '''16''', p. 101.</ref>
<ref name = R-T>{{cite journal |last1=Reimer |first1=Karl |last2=Tiemann |first2=Ferdinand |author-link2=Ferdinand Tiemann |title=Ueber die Einwirkung von Chloroform auf alkalische Phenolate |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1876 |volume=9 |pages=824–828 |doi=10.1002/cber.187600901247 |url=https://zenodo.org/record/1425102 |trans-title=The effect of chloroform on phenol and especially on the alkaline solution of aromatic oxyacids |language=German}}</ref><ref>{{cite journal|last1=Reimer|first1=K.|last2=Tiemann|first2=Ferdinand |author-link2=Ferdinand Tiemann |title=Ueber die Einwirkung von Chloroform auf Phenole und besonders aromatische Oxysäuren in alkalischer Lösung|journal=Berichte der Deutschen Chemischen Gesellschaft|year=1876|volume=9|issue=2|pages=1268–1278|doi=10.1002/cber.18760090270|url=https://babel.hathitrust.org/cgi/pt?id=hvd.cl1hz1;view=1up;seq=240|trans-title=On the effect of chloroform on phenols and particularly aromatic oxyacids in alkaline solution}}</ref>  The early work has been reviewed.<ref>{{cite journal|last=Wynberg|first=Hans|title=The Reimer-Tiemann Reaction|journal=Chemical Reviews|year=1960|volume=60|issue=2|pages=169–184|doi=10.1021/cr60204a003}}</ref>

==References==
{{reflist|3}}
{{Organic reactions}}
{{DEFAULTSORT:Reimer-Tiemann reaction}}
[[Category:Addition reactions]]
[[Category:Carbon-carbon bond forming reactions]]
[[Category:Name reactions]]
[[Category:Formylation reactions]]