Editing Pyrrole (section)

==Reactions and reactivity==
Due to its [[Aromaticity|aromatic character]], pyrrole is difficult to [[hydrogenate]], does not easily react as a [[diene]] in [[Diels–Alder]] reactions, and does not undergo usual [[olefin]] reactions. Its reactivity is similar to that of [[benzene]] and [[aniline]], in that it is easy to alkylate and acylate. Under acidic conditions, pyrroles [[oxidize]] easily to [[polypyrrole]],<ref>{{cite book|editor1=Wang Jitao [王积涛]|editor2=Zhang Baoshen [张保申]|editor3=Wang Yongmei [王永梅]|editor4=Hu Qingmei [胡青眉]|year=2003|script-title=zh:有机化学|lang=zh|trans-title=Organic Chemistry|edition=2nd|publisher=Tianjin Nankai University|isbn=978-7-310-00620-5}}</ref> {{Citation needed|date=April 2025}}and thus many [[Electrophile|electrophilic]] reagents that are used in benzene chemistry are not applicable to pyrroles. In contrast, substituted pyrroles (including [[protecting group|protected]] pyrroles) have been used in a broad range of transformations.<ref name="Lubell"/>

===Reaction of pyrrole with electrophiles===
Pyrroles generally react with electrophiles at the α position (C2 or C5), due to the highest degree of stability of the protonated intermediate. 
[[File:Pyrrole Electrophilic Substitution.png|500px|center|class=skin-invert-image|Pyrrole electrophilic substitution]]  Pyrroles react easily with [[Nitrate|nitrating]] (e.g. [[Nitric acid|HNO<sub>3</sub>]]/[[Acetic anhydride|Ac<sub>2</sub>O]]), [[Sulfonate|sulfonating]] ([[Sulfur trioxide pyridine complex|Py·SO<sub>3</sub>]]), and [[halogen]]ating (e.g. [[N-Chlorosuccinimide|NCS]], [[N-Bromosuccinimide|NBS]], [[Bromine|Br<sub>2</sub>]], [[Sulfonyl chloride|SO<sub>2</sub>Cl<sub>2</sub>]], and [[Potassium iodide|KI]]/[[Hydrogen peroxide|H<sub>2</sub>O<sub>2</sub>]]) agents.<ref>{{cite encyclopedia|entry=Pyrrol|encyclopedia=Römpp Lexikon Chemie|trans-title=Römpp's Chemical Lexicon|publisher=Thieme|lang=de}}</ref> Halogenation generally provides polyhalogenated pyrroles, but monohalogenation can be performed. As is typical for electrophilic additions to pyrroles, halogenation generally occurs at the 2-position, but can also occur at the 3-position by silation of the nitrogen. This is a useful method for further functionalization of the generally less reactive 3-position.{{citation needed|date=July 2016}}

====Acylation====
[[Acylation]] generally occurs at the 2-position, through the use of various methods. Acylation with [[acid anhydride]]s and [[acid chloride]]s can occur with or without a catalyst.<ref>{{cite journal |doi=10.15227/orgsyn.051.0100 |title=Ethyl Pyrrole-2-Carboxylate |journal=Organic Syntheses |date=1971 |volume=51 |page=100|first1=Denis M.|last1=Bailey|first2=Robert E.|last2=Johnson|first3=Noel F.|last3=Albertson }}</ref> 2-Acylpyrroles are also obtained from reaction with nitriles, by the [[Houben–Hoesch reaction]]. Pyrrole aldehydes can be formed by a [[Vilsmeier–Haack reaction]].<ref>{{cite journal |doi=10.15227/orgsyn.036.0074 |title=2-Pyrrolealdehyde |journal=Organic Syntheses |date=1956 |volume=36 |page=74|first1=Robert M.|last1=Silverstein|first2=Edward E.|last2=Ryskiewicz|first3=Constance|last3=Willard
 }}</ref> 
[[File:PyrroleFormylation.png|400px|center|class=skin-invert-image|Vilsmeier–Haack formylation of pyrrole]]

===Reaction of deprotonated pyrrole===
The NH proton in pyrroles is moderately acidic with a [[Acid dissociation constant|p''K''<sub>a</sub>]] of 17.5.<ref>{{cite book|first1=C.&nbsp;W.|last1=Bird|first2=G.&nbsp;W.&nbsp;H.|last2=Cheeseman|title=Comprehensive Heterocyclic Chemistry|url=http://www.sciencedirect.com/science/article/pii/B9780080965192000527|publisher=Pergamon|year=1984|pages=39–88|isbn=978-0-08-096519-2|postscript=None}}, although note that {{cite journal|doi=10.1016/S0040-4020(01)89212-7|journal=Tetrahedron|volume=45|issue=23|pages=7501–7504|year=1989|publisher=Pergamon|location=Great Britain|title=The acid-base properties of pyrrole and its benzologs indole and carbazole: a re-examination from the excess acidity method|first1=M.|last1=Balón|first2=M.&nbsp;C.|last2=Carmona|first3=M.&nbsp;A.|last3=Muñoz|first4=J.|last4=Hidalgo|postscript=None}} suggests that figure's revision to 17.3.</ref> Pyrrole can be deprotonated with strong bases such as [[butyllithium]] and [[sodium hydride]].<ref>{{cite book|first1=Heinz-Gerhard|last1=Franck|first2=Jürgen&nbsp;Walter|last2=Stadelhofer|title=Industrielle Aromatenchemie: Rohstoffe, Verfahren, Produkte|trans-title=Industrial Chemistry of the Aromatics: Raw materials, processes, products|lang=de|publisher=Springer|location=Berlin|year=1987|isbn=978-3-662-07876-1|pages=403–404}}</ref> The resulting alkali pyrrolide is [[nucleophilic]]. Treating this conjugate base with an electrophile such as [[iodomethane]] gives ''N''-methylpyrrole. 

''N''-Metalated pyrrole can react with electrophiles at the N or C positions, depending on the coordinating metal. More ionic nitrogen–metal bonds (such as with lithium, sodium, and potassium) and more solvating solvents lead to ''N''-alkylation. Nitrophilic metals, such as MgX, lead to alkylation at C (mainly C2), due to a higher degree of coordination to the nitrogen atom.  In the cases of ''N''-substituted pyrroles, metalation of the carbons is more facile. Alkyl groups can be introduced as electrophiles, or by cross-coupling reactions.{{citation needed|date=July 2016}} 
[[File:Pyrrole C Metallation.jpg|center|class=skin-invert-image|Pyrrole ''C''-metalation]]

Substitution at C3 can be achieved through the use of ''N''-substituted 3-bromopyrrole, which can be synthesized by bromination of ''N''-silylpyrrole with [[N-Bromosuccinimide|NBS]].{{citation needed|date=July 2016}}

===Reductions===
Pyrroles can undergo reductions to [[pyrrolidines]] and to [[pyrrolines]].<ref>{{cite book|author=Lyastukhin, Voronov [Ластухін, Воронов]|year=2006|script-title=uk:Органічна хімія|url=https://archive.org/details/isbn_9667022196|lang=uk|trans-title=Organic Chemistry|pages=781–782|isbn=966-7022-19-6}}</ref> For example, [[Birch reduction]] of pyrrole esters and amides produced pyrrolines, with the regioselectivity depending on the position of the electron-withdrawing group.{{citation needed|date=July 2016}}

===Cyclization reactions===
Pyrroles with ''N''-substitution can undergo [[cycloaddition]] reactions such as [4+2]-, [2+2]-, and [2+1]-cyclizations. Diels-Alder cyclizations can occur with the pyrrole acting as a diene, especially in the presence of an electron-withdrawing group on the nitrogen. Vinylpyrroles can also act as dienes.{{citation needed|date=July 2016}} 
[[File:Pyrrole DA.svg|center|class=skin-invert-image|300px|Pyrrole DA]]

Pyrroles can react with [[carbene]]s, such as [[dichlorocarbene]], in a [2+1]-cycloaddition. With [[dichlorocarbene]], a dichlorocyclopropane intermediate is formed, which breaks down to form [[3-Chloropyridine|3-chloropyridine]] (the Ciamician–Dennstedt rearrangement).<ref>{{cite journal|last1=Ciamician |first1=G. L. |last2=Dennstedt |first2=M. |title=Ueber die Einwirkung des Chloroforms auf die Kaliumverbindung Pyrrols |trans-title=On the reaction of chloroform with the potassium compound of pyrrole |journal=Berichte der Deutschen Chemischen Gesellschaft  |volume=14 |pages=1153–1162 |date=1881 |url=https://babel.hathitrust.org/cgi/pt?id=hvd.cl1hza;view=1up;seq=1223 |doi=10.1002/cber.188101401240}}</ref><ref>{{cite book|last=Corwin |first=Alsoph Henry |editor-first=Robert Cooley |editor-last=Elderfield |title=Heterocyclic Compounds |volume=1 |location=New York, NY |publisher=Wiley |date=1950 |page=309}}</ref><ref>{{cite book|last=Mosher|first=H. S.  |editor-first=Robert Cooley |editor-last=Elderfield |title=Heterocyclic Compounds |volume=1 |location=New York, NY |publisher=Wiley |date=1950 |page=475}}</ref> 
[[File:Ciamician-Dennstedt Rearrangement.png|500px|center|class=skin-invert-image|Ciamician–Dennstedt rearrangement]]