View source for Hunsdiecker reaction

{{Short description|Named reaction for synthesis of organic halides}}
{{Reactionbox
| Name = Hunsdiecker reaction
| Type = Substitution reaction
| NamedAfter = [[Heinz Hunsdiecker]] <br /> [[Cläre Hunsdiecker]] <br /> [[Alexander Borodin]]
| Section3 = {{Reactionbox Identifiers
   | OrganicChemistryNamed = hunsdiecker-reaction
   | RSC_ontology_id = 0000106
 }}
}}
The '''Hunsdiecker reaction''' (also called the '''Borodin reaction''' or the '''Hunsdiecker&ndash;Borodin reaction''') is a [[name reaction]] in [[organic chemistry]] whereby [[silver]] salts of [[carboxylic acid]]s react with a [[halogen]] to produce an [[organic halide]].<ref name = JJL />  It is an example of both a [[decarboxylation]] and a [[halogenation]] reaction as the product has one fewer carbon atoms than the starting material (lost as [[carbon dioxide]]) and a halogen atom is introduced its place.<ref name = Johnson1956 /><ref name = Wilson1957 /> A [[catalysis|catalytic]] approach has been developed.<ref name = Catalytic />

:[[Image:Hunsdiecker Reaction Scheme.png|400px|The Hunsdiecker reaction]]

==History==
The reaction is named after [[Cläre Hunsdiecker]] and her husband [[Heinz Hunsdiecker]], whose work in the 1930s<ref name = Patent1939>{{cite patent|title = Method of manufacturing organic chlorine and bromine derivatives|country = US|number = 2176181|status = patent|pubdate = 1939-10-17|fdate = 1936-04-02|pridate = 1935-04-08|inventorlink1 = Cläre Hunsdiecker|inventor1-last = Hunsdiecker|inventor1-first = C.|inventor2-last = Vogt|inventor2-first = E.|inventorlink3 = Heinz Hunsdiecker|inventor3-last = Hunsdiecker|inventor3-first = H.|url = https://www.google.com/patents/US2176181|assign1 = Hunsdiecker, C.; Vogt, E.; Hunsdiecker, H.}}</ref><ref name = ChemBer1941>{{cite journal|first1 = H.|last1 = Hunsdiecker|authorlink1  = Heinz Hunsdiecker|first2 = C.|last2 = Hunsdiecker|authorlink2 = Cläre Hunsdiecker|journal = [[Chemische Berichte]]|year = 1942|volume = 75|issue = 3|pages = 291–297|doi = 10.1002/cber.19420750309|title = Über den Abbau der Salze aliphatischer Säuren durch Brom|language = German|trans-title = About the degradation of salts of aliphatic acids by bromine}}</ref> developed it into a general method.<ref name = JJL />
The reaction was first demonstrated by [[Alexander Borodin]] in 1861 in his reports of the preparation of [[methyl bromide]] ({{chem2|CH3Br}}) from [[silver acetate]] ({{chem2|CH3CO2Ag}}).<ref name = Borodin1861a /><ref name = Borodin1861b /> Around the same time, Angelo Simonini, working as a student of [[Adolf Lieben]] at the [[University of Vienna]], investigated the reactions of silver carboxylates with [[iodine]].<ref name = Johnson1956 />  They found that the products formed are determined by the [[stoichiometry]] within the reaction mixture.  Using a carboxylate-to-iodine ratio of 1:1 leads to an alkyl iodide product, in line with Borodin's findings and the modern understanding of the Hunsdiecker reaction.  However, a 2:1 ratio favours the formation of an [[ester]] product that arises from decarboxylation of one carboxylate and coupling the resulting alkyl chain with the other.<ref name = Simonini1892 /><ref name = Simonini1893 />

:[[Image:Simonini Reaction Scheme.png|300px|The Simonini reaction]]

Using a 3:2 ratio of reactants leads to the formation of a 1:1 mixture of both products.<ref name = Simonini1892 /><ref name = Simonini1893 />  These processes are sometimes known as the '''Simonini reaction''' rather than as modifications of the Hunsdiecker reaction.<ref name = Johnson1956 /><ref name = Wilson1957 />

:3&nbsp;{{chem|R|COO||Ag}}  +  2&nbsp;{{chem|I|2}}  →  {{chem|RI}}  +  {{chem|RCOO||R}}  +  2&nbsp;{{chem|CO|2}}  +  3&nbsp;{{chem|AgI}}

==Reaction mechanism==
In terms of [[reaction mechanism]], the Hunsdiecker reaction is believed to involve [[Radical (chemistry)|organic radical]] intermediates. The silver salt '''1''' reacts with bromine to form the acyl hypohalite intermediate '''2'''. Formation of the [[diradical]] pair '''3''' allows for radical [[decarboxylation]] to form the diradical pair '''4''', which recombines to form the organic halide '''5'''. The trend in the yield of the resulting halide is primary&nbsp;>&nbsp;secondary&nbsp;>&nbsp;tertiary.<ref name = Johnson1956 /><ref name = Wilson1957 />

:[[File:Hunsdiecker Reaction Mechanism.png|Radicalic mechanism of Hunsdiecker reaction|650px]]

==Variations==
The reaction cannot be performed in [[protic solvent]]s, as these induce decomposition of the intermediate [[acetyl]] [[hypohalite]].{{cite needed|date=September 2023}}  

Other [[counterion]]s than silver typically have slow reaction rates.  The toxic<ref name=CRDrawbacks /> relativistic metals ([[mercury (element)|mercury]], [[thallium]], and [[lead]]) are preferred: inert counterions, such as the [[alkali metal]]s, have only rarely led to reported success.<ref name=Patai>{{cite book|pages=463–471|title=The chemistry of acyl halides|editor-last=Patai|editor-first=Saul|series=The Chemistry of Functional Groups|year=1972|publisher=John Wright & Sons / Interscience|place=Bristol / London|lccn=70-37114|isbn=0-471-66936-9|chapter=The acyl hypohalites|last1=Tanner|first1=Denis&nbsp;D.|last2=Bunce|first2=Nigel&nbsp;J.|doi=10.1002/9780470771273|url=https://archive.org/details/pataischemistryoffunctionalgroupsacylhalides1972/|via=the [[Internet Archive]]}}</ref>{{rp|464}}  The [[Kochi reaction]] is a variation on the Hunsdiecker reaction developed by [[Jay Kochi]] that uses [[lead(IV) acetate]] and [[lithium chloride]] ([[lithium bromide]] can also be used) to effect the halogenation and decarboxylation.<ref name = Kochi />
[[Image:Kochi reaction.svg|frameless|center|The Kochi reaction|250px]]

In the presence of [[multiple bond]]s, the intermediate acetyl hypohalite prefers to add to the bond, producing an α-haloester.   Steric considerations suppress this tendency in α,β-unsaturated carboxylic acids, which instead polymerize (see below).<ref name=Patai />{{rp|468}}  

[[Mercuric oxide]] and [[bromine]] convert 3-chlorocyclobutanecarboxylic acid  to 1-bromo-3-chlorocyclobutane. This is known as Cristol-Firth modification.<ref name = Lampman1971a /><ref name = Lampman1971b /><ref name = C3H5Br /> The 1,3-dihalocyclobutanes were key precursors to [[propellane]]s.<ref name = Wiberg1965>{{cite journal|first1 = K. B.|last1 = Wiberg|authorlink1 = Kenneth B. Wiberg|first2 = G. M.|last2 = Lampman|first3 = R. P.|last3 = Ciula|first4 = D. S.|last4 = Connor|first5 = P.|last5 = Schertler|first6 = J.|last6 = Lavanish|title = Bicyclo[1.1.0]butane|journal = [[Tetrahedron (journal)|Tetrahedron]]|year = 1965|volume = 21|issue = 10|pages = 2749–2769|doi = 10.1016/S0040-4020(01)98361-9}}</ref> The reaction has been applied to the preparation of ω-bromo [[ester]]s with chain lengths between five and seventeen carbon atoms, with the preparation of methyl 5-bromovalerate published in ''[[Organic Syntheses]]'' as an exemplar.<ref name = Omega-bromo />

=== Reaction with α,β-unsaturated carboxylic acids ===
[[File:Microwave-Induced_Hunsdiecker_Rxn_with_NXS.png|alt=|thumb|424x424px|Synthesis of β-arylvinyl halide by microwave-induced Hunsdiecker reaction.]]
For unsaturated conmpounds, the radical conditions associated with the Hunsdiecker reaction can also induce [[polymerization]] instead of decarboxylation.<ref name=Patai />{{rp|468}}  Consequently, reactions with [[Α,β-Unsaturated carbonyl compound|α,β-unsaturated]] carboxylic acids typically give low yield.<ref name=CRDrawbacks>{{Cite journal|last1=Chowdhury|first1=Shantanu|last2=Roy|first2=Sujit|date=1997-01-01|title=The First Example of a Catalytic Hunsdiecker Reaction: Synthesis of β-Halostyrenes|journal=The Journal of Organic Chemistry|volume=62|issue=1|pages=199–200|doi=10.1021/jo951991f|pmid=11671382|issn=0022-3263}}</ref> Kuang ''et al'' have found that an alternate radical halogenating agent, N-halosuccinimide, combined with a [[lithium acetate]] catalyst, gives a higher yield of β-halostyrenes. The reaction also improves in the presence of [[Microwave chemistry|microwave irradiation]], which preferentially synthesizes (''E'')-β-arylvinyl halides.<ref name=":0">{{Cite journal|last1=Kuang|first1=Chunxiang|last2=Senboku|first2=Hisanori|last3=Tokuda|first3=Masao|date=2000|title=Stereoselective Synthesis of (E)-β-Arylvinyl Halides by Microwave-Induced Hunsdiecker Reaction|journal=Synlett|language=en|volume=2000|issue=10|pages=1439–1442|doi=10.1055/s-2000-7658|issn=0936-5214}}</ref> 

For a [[Green chemistry|green]] metal-free reaction, [[tetrabutylammonium trifluoroacetate]] serves as an alternative catalyst.<ref>{{Cite journal|last1=Naskar|first1=Dinabandhu|last2=Chowdhury|first2=Shantanu|last3=Roy|first3=Sujit|date=1998-02-12|title=Is metal necessary in the Hunsdiecker-Borodin reaction?|url=http://www.sciencedirect.com/science/article/pii/S0040403997106396|journal=Tetrahedron Letters|language=en|volume=39|issue=7|pages=699–702|doi=10.1016/S0040-4039(97)10639-6|issn=0040-4039}}</ref>  However, it only exhibits comparable yields to the original lithium acetate when performed with [[micellar solubilization|micellular surfactants]].<ref name=":0" /><ref>{{Cite journal|last1=Das|first1=Jaya Prakash|last2=Roy|first2=Sujit|date=2002-11-01|title=Catalytic Hunsdiecker Reaction of α,β-Unsaturated Carboxylic Acids: How Efficient Is the Catalyst?|journal=The Journal of Organic Chemistry|volume=67|issue=22|pages=7861–7864|doi=10.1021/jo025868h|pmid=12398515|issn=0022-3263}}</ref><ref>{{Cite journal|last1=Rajanna|first1=K. C.|last2=Reddy|first2=N. Maasi|last3=Reddy|first3=M. Rajender|last4=Saiprakash|first4=P. K.|date=2007-04-01|title=Micellar Mediated Halodecarboxylation of α,β-Unsaturated Aliphatic and Aromatic Carboxylic Acids—A Novel Green Hunsdiecker–Borodin Reaction|journal=Journal of Dispersion Science and Technology|volume=28|issue=4|pages=613–616|doi=10.1080/01932690701282690|s2cid=96943205|issn=0193-2691}}</ref>

==See also==
*[[Barton decarboxylation]]
*[[Barton–McCombie deoxygenation]]

==References==
{{Reflist|refs =

<ref name = Borodin1861a>{{cite journal|first = A.|last = Borodin|authorlink = Alexander Borodin|journal = [[Annalen der Chemie und Pharmacie]]|year = 1861|volume = 119|pages = 121–123|doi = 10.1002/jlac.18611190113|title = Ueber Bromvaleriansäure und Brombuttersäure|language = German|trans-title = About bromovaleric acid and bromobutyric acid|url = https://zenodo.org/record/1427169}}</ref>

<ref name = Borodin1861b>{{cite journal|first = A.|last = Borodin|authorlink = Alexander Borodin|journal = [[Zeitschrift für Chemie und Pharmacie]]|year = 1861|volume = 4|pages = 5–7|url = https://babel.hathitrust.org/cgi/pt?id=uc1.b3645096;view=1up;seq=39|title = Ueber de Monobrombaldriansäure und Monobrombuttersäure|language = German|trans-title = About the monobromovaleric acid and monobromobutyric acid}}</ref>

<ref name = C3H5Br>{{OrgSynth|title = Bromocyclopropane|last1 = Meek|first1 = J. S.|last2 = Osuga|first2 = D. T.|volume = 43|pages = 9|collvol = 5|collvolpages = 126|year = 1963|prep = cv5p0126|doi = 10.15227/orgsyn.043.0009|abbr = yes}}</ref>

<ref name = Catalytic>{{cite journal|title = Silver-Catalyzed Decarboxylative Chlorination of Aliphatic Carboxylic Acids|first1 = Zhentao|last1 = Wang|first2 = Lin|last2 = Zhu|first3 = Feng|last3 = Yin|first4 = Zhongquan|last4 = Su|first5 = Zhaodong|last5 = Li|first6 = Chaozhong|last6 = Li|journal = [[Journal of the American Chemical Society]]|year = 2012|volume = 134|issue = 9|pages = 4258–4263|doi = 10.1021/ja210361z|pmid = 22316183}}</ref>

<ref name = JJL>{{cite book|title = Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications|edition = 5th|publisher = [[Springer Science & Business Media]]|pages = 327–328|first = J. J.|last = Li|chapter = Hunsdiecker&ndash;Borodin Reaction|chapter-url = https://books.google.com/books?id=HoXBBAAAQBAJ&pg=PA327|isbn = 9783319039794|date = 2014-01-30}}</ref>

<ref name = Johnson1956>{{cite journal|last1 = Johnson|first1 = R. G.|last2 = Ingham|first2 = R. K.|journal = [[Chem. Rev.]]|year = 1956|volume = 56|issue = 2|pages = 219–269|doi = 10.1021/cr50008a002|title = The Degradation of Carboxylic Acid Salts by Means of Halogen &ndash; the Hunsdiecker Reaction}}</ref>

<ref name = Kochi>{{cite journal|title = A New Method for Halodecarboxylation of Acids Using Lead(IV) Acetate|first = J. K.|last = Kochi|authorlink = Jay Kochi|journal = [[Journal of the American Chemical Society]]|year = 1965|volume = 87|issue = 11|pages = 2500–2502|doi = 10.1021/ja01089a041}}</ref>

<ref name = Lampman1971a>{{OrgSynth|year = 1971|title = Mercury(II) oxide-modified Hunsdiecker reaction: 1-Bromo-3-chlorocyclobutane|last1 = Lampman|first1 = G. M.|last2 = Aumiller|first2 = J. C.|volume = 51|pages = 106|abbr = yes|collvol = 6|collvolpages = 179|prep = cv6p0179|doi = 10.15227/orgsyn.051.0106}}</ref>

<ref name = Lampman1971b>{{OrgSynth|first1 = G. M.|last1 = Lampman|first2 = J. C.|last2 = Aumiller|title = Bicyclo[1.1.0]butane|year = 1971|volume = 51 |pages = 55|prep = CV6P0133|collvol = 6|collvolpages = 133|abbr = yes|doi = 10.15227/orgsyn.051.0055}}</ref>

<ref name = Omega-bromo>{{OrgSynth|title = Methyl 5-bromovalerate (Valeric acid, δ-bromo-, methyl ester)|last1 = Allen|first1 = C. F. H.|last2 = Wilson|first2 = C. V.|collvol = 3|collvolpages = 578|year = 1946|prep = cv3p0578|volume = 26|pages = 52|abbr = yes|doi = 10.15227/orgsyn.026.0052}}</ref>

<ref name = Simonini1892>{{cite journal|title = Über den Abbau der fetten Säuren zu kohlenstoffärmeren Alkoholen|language = German|trans-title = About the breakdown of fatty acids to lower carbon alcohols|last = Simonini|first = A.|journal = Monatshefte für Chemie und verwandte Teile anderer Wissenschaften|year = 1892|volume = 13|issue = 1|pages = 320–325|doi = 10.1007/BF01523646|s2cid = 197766447}}</ref>

<ref name = Simonini1893>{{cite journal|title = Über den Abbau der fetten Säuren zu kohlenstoffärmeren Alkoholen|language = German|trans-title = About the breakdown of fatty acids to lower carbon alcohols|last = Simonini|first = A.|journal = Monatshefte für Chemie und verwandte Teile anderer Wissenschaften|year = 1893|volume = 14|issue = 1|pages = 81–92|doi = 10.1007/BF01517859|s2cid = 104367588}}</ref>

<ref name = Wilson1957>{{cite journal|last = Wilson|first = C. V.|journal = [[Org. React.]]|year = 1957|volume = 9|pages = 332–387|title = The Reaction of Halogens with Silver Salts of Carboxylic Acids|doi = 10.1002/0471264180.or009.05|isbn = 0471264180}}</ref>

}}

== External links ==
* [https://commons.wikimedia.org/wiki/File:Hundsdiecker_startAnimGif.gif Animation of the reaction mechanism]
{{Organic reactions}}
{{DEFAULTSORT:Hunsdiecker Reaction}}
[[Category:1861 in science]]
[[Category:1861 introductions]]
[[Category:Free radical reactions]]
[[Category:Halogenation reactions]]
[[Category:Name reactions]]