Hunsdiecker reaction

The Hunsdiecker reaction (also called the Borodin reaction or the Hunsdiecker–Borodin reaction) is a name reaction in organic chemistry whereby silver salts of carboxylic acids react with a halogen to produce an organic halide.[1] 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. The reaction was first demonstrated by Alexander Borodin in his 1861 reports of the preparation of methyl bromide ( CH3Br ) from silver acetate ( CH3CO2Ag ).[2][3] Shortly after, the approach was applied to the degradation of fatty acids in the laboratory of Adolf Lieben.[4][5] However, it is named for Cläre Hunsdiecker and her husband Heinz Hunsdiecker, whose work in the 1930s[6][7] developed it into a general method.[1] Several reviews have been published,[8][9] and a catalytic approach has been developed.[10]

Hunsdiecker reaction
Named after Heinz Hunsdiecker
Cläre Hunsdiecker
Alexander Borodin
Reaction type Substitution reaction
Identifiers
Organic Chemistry Portal hunsdiecker-reaction
RSC ontology ID RXNO:0000106
The Hunsdiecker reaction

HistoryEdit

Alexander Borodin first observed the reaction in 1861 when he prepared methyl bromide from silver acetate.[2][3] The reaction is a decarboxylation in that alkyl halide product has one fewer carbon atoms than its parent carboxylate, lost as carbon dioxide.[1][8]

CH
3
CO
2
Ag
  +   Br
2
  →   CH
3
Br
  +   CO
2
  +   AgBr

Around the same time, Angelo Simonini was working as a student of Adolf Lieben at the University of Vienna, investigating the reactions of silver carboxylates with iodine.[8] 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.[4][5]

 

Using a 3:2 ratio of reactants leads to the formation of a 1:1 mixture of both products.[4][5] These processes are sometimes known as the Simonini reaction rather than as modifications of the Hunsdiecker reaction.[8][9]

RCO
2
Ag
  +   2 I
2
  →   RI   +   RCO
2
R
  +   2 CO
2
  +   3 AgI

It is now well established that mercuric oxide can also be used to effect this transformation.[11][12] The reaction has been applied to the preparation of ω-bromo esters with chain lengths between five and seventeen carbon atoms, with the preparation of methyl 5-bromovalerate published in Organic Syntheses as an exemplar.[13]

Reaction mechanismEdit

The reaction mechanism of the Hunsdiecker reaction is believed to involve organic radical intermediates. The silver salt of the carboxylic acid 1 will quickly react with bromine to form acyl hypohalite intermediate 2. Formation of the diradical pair 3 allows for radical decarboxylation to form the diradical pair 4, which will quickly recombine to form the desired organic halide 5. The trend in the yield of the resulting halide is primary > secondary > tertiary.[8][9]

 

Reaction with α, β-Unsaturated Carboxylic AcidsEdit

 
Synthesis of β-arylvinyl halide by microwave-induced Hunsdiecker reaction.

Chowdhury and Roy noted several drawbacks of using Hunsdiecker reaction, namely that some reagents, such as molecular bromine and salts of mercury, thallium, lead, and silver, are inherently toxic and that reactions with α, β-unsaturated carboxylic acids result in low yield.[14] Regarding reactions using α, β-unsaturated carboxylic acids, Kuang et al. modified the reaction with using a new halogenating agent, N-halosuccinimide, and lithium acetate as the catalyst, which resulted in higher yield of β-Halostyrenes.[15] They found that using the microwave irradiation could synthesize (E)-β-arylvinyl halide much quicker with higher yields.[15] This is useful because synthesizing (E)-vinyl bromide in general is not very practical due to the complexity of alternative reagents (e.g. organometallic compounds), longer reaction times, and lower yields.[16] Using microwave irradiation also allows the synthesized arylvinyl halide to carry electron-donating groups (in addition to electron-withdrawing groups), which is not possible with alternative synthetic methods.[16] While tetrabutylammonium trifluoroacetate (TBATFA) could be used as an alternative catalyst for a metal-free reaction,[17] it was noted that lithium acetate resulted in higher yields compared to other relatively complex catalysts, including tetrabutylammonium trifluoroacetate.[15][18] An alternative method using micelles was found, with green characteristics.[19] Micelles generally facilitate reactions thanks to their solublization capability and here, it was found that a reaction with α, β-unsaturated aromatic carboxylic acids and N-halosuccinimide catalyzed by cetyl trimethyl ammonium bromide (CTAB), sodium dodecyl sulfate (SDS), and Triton-X-100 in dichloroethane (DCE) carried out under reflux conditions of 20–60 minutes formed β-Halostyrenes in excellent yields with high regioselectivity.

VariationsEdit

Mercuric oxideEdit

Lampman and Aumiller used mercuric oxide and bromine to prepare 1-bromo-3-chlorocyclobutane from 3-chlorocyclobutanecarboxylic acid in a modification of the Hunsdiecker reaction.This is known as Cristol-Firth modification.[12] The product had previously been shown by Wiberg to react with molten sodium metal to form bicyclobutane via a Wurtz coupling in good yield.[20][21]

Kochi reactionEdit

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.[22]

 

See alsoEdit

ReferencesEdit

  1. ^ a b c Li, J. J. (2014-01-30). "Hunsdiecker–Borodin Reaction". Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications (5th ed.). Springer Science & Business Media. pp. 327–328. ISBN 9783319039794.
  2. ^ a b Borodin, A. (1861). "Ueber Bromvaleriansäure und Brombuttersäure" [About bromovaleric acid and bromobutyric acid]. Annalen der Chemie und Pharmacie (in German). 119: 121–123. doi:10.1002/jlac.18611190113.
  3. ^ a b Borodin, A. (1861). "Ueber de Monobrombaldriansäure und Monobrombuttersäure" [About the monobromovaleric acid and monobromobutyric acid]. Zeitschrift für Chemie und Pharmacie (in German). 4: 5–7.
  4. ^ a b c Simonini, A. (1892). "Über den Abbau der fetten Säuren zu kohlenstoffärmeren Alkoholen" [About the breakdown of fatty acids to lower carbon alcohols]. Monatshefte für Chemie und verwandte Teile anderer Wissenschaften (in German). 13 (1): 320–325. doi:10.1007/BF01523646. S2CID 197766447.
  5. ^ a b c Simonini, A. (1893). "Über den Abbau der fetten Säuren zu kohlenstoffärmeren Alkoholen" [About the breakdown of fatty acids to lower carbon alcohols]. Monatshefte für Chemie und verwandte Teile anderer Wissenschaften (in German). 14 (1): 81–92. doi:10.1007/BF01517859. S2CID 104367588.
  6. ^ US patent 2176181, Hunsdiecker, C.; E. Vogt & H. Hunsdiecker, "Method of manufacturing organic chlorine and bromine derivatives", published 1939-10-17, assigned to Hunsdiecker, C.; Vogt, E.; Hunsdiecker, H. 
  7. ^ Hunsdiecker, H.; Hunsdiecker, C. (1942). "Über den Abbau der Salze aliphatischer Säuren durch Brom" [About the degradation of salts of aliphatic acids by bromine]. Chemische Berichte (in German). 75 (3): 291–297. doi:10.1002/cber.19420750309.
  8. ^ a b c d e Johnson, R. G.; Ingham, R. K. (1956). "The Degradation of Carboxylic Acid Salts by Means of Halogen – the Hunsdiecker Reaction". Chem. Rev. 56 (2): 219–269. doi:10.1021/cr50008a002.
  9. ^ a b c Wilson, C. V. (1957). "The Reaction of Halogens with Silver Salts of Carboxylic Acids". Org. React. 9: 332–387. doi:10.1002/0471264180.or009.05. ISBN 0471264180.
  10. ^ Wang, Zhentao; Zhu, Lin; Yin, Feng; Su, Zhongquan; Li, Zhaodong; Li, Chaozhong (2012). "Silver-Catalyzed Decarboxylative Chlorination of Aliphatic Carboxylic Acids". Journal of the American Chemical Society. 134 (9): 4258–4263. doi:10.1021/ja210361z. PMID 22316183.
  11. ^ Meek, J. S.; Osuga, D. T. (1963). "Bromocyclopropane". Org. Synth. 43: 9. doi:10.15227/orgsyn.043.0009.; Coll. Vol., 5, p. 126
  12. ^ a b Lampman, G. M.; Aumiller, J. C. (1971). "Mercury(II) oxide-modified Hunsdiecker reaction: 1-Bromo-3-chlorocyclobutane". Org. Synth. 51: 106. doi:10.15227/orgsyn.051.0106.; Coll. Vol., 6, p. 179
  13. ^ Allen, C. F. H.; Wilson, C. V. (1946). "Methyl 5-bromovalerate (Valeric acid, δ-bromo-, methyl ester)". Org. Synth. 26: 52. doi:10.15227/orgsyn.026.0052.; Coll. Vol., 3, p. 578
  14. ^ Chowdhury, Shantanu; Roy, Sujit (1997-01-01). "The First Example of a Catalytic Hunsdiecker Reaction: Synthesis of β-Halostyrenes". The Journal of Organic Chemistry. 62 (1): 199–200. doi:10.1021/jo951991f. ISSN 0022-3263. PMID 11671382.
  15. ^ a b c Kuang, Chunxiang; Senboku, Hisanori; Tokuda, Masao (2000). "Stereoselective Synthesis of (E)-β-Arylvinyl Halides by Microwave-Induced Hunsdiecker Reaction". Synlett. 2000 (10): 1439–1442. doi:10.1055/s-2000-7658. ISSN 0936-5214.
  16. ^ a b Kuang, Chunxiang; Yang, Qing; Senboku, Hisanori; Tokuda, Masao (May 2005). "Stereoselective Synthesis of (E)-β-Arylvinyl Bromides by Microwave-Induced Hunsdiecker-Type Reaction". Synthesis. 2005 (8): 1319–1325. doi:10.1055/s-2005-865283. ISSN 0039-7881.
  17. ^ Naskar, Dinabandhu; Chowdhury, Shantanu; Roy, Sujit (1998-02-12). "Is metal necessary in the Hunsdiecker-Borodin reaction?". Tetrahedron Letters. 39 (7): 699–702. doi:10.1016/S0040-4039(97)10639-6. ISSN 0040-4039.
  18. ^ Das, Jaya Prakash; Roy, Sujit (2002-11-01). "Catalytic Hunsdiecker Reaction of α,β-Unsaturated Carboxylic Acids: How Efficient Is the Catalyst?". The Journal of Organic Chemistry. 67 (22): 7861–7864. doi:10.1021/jo025868h. ISSN 0022-3263. PMID 12398515.
  19. ^ Rajanna, K. C.; Reddy, N. Maasi; Reddy, M. Rajender; Saiprakash, P. K. (2007-04-01). "Micellar Mediated Halodecarboxylation of α,β‐Unsaturated Aliphatic and Aromatic Carboxylic Acids—A Novel Green Hunsdiecker–Borodin Reaction". Journal of Dispersion Science and Technology. 28 (4): 613–616. doi:10.1080/01932690701282690. ISSN 0193-2691. S2CID 96943205.
  20. ^ Wiberg, K. B.; Lampman, G. M.; Ciula, R. P.; Connor, D. S.; Schertler, P.; Lavanish, J. (1965). "Bicyclo[1.1.0]butane". Tetrahedron. 21 (10): 2749–2769. doi:10.1016/S0040-4020(01)98361-9.
  21. ^ Lampman, G. M.; Aumiller, J. C. (1971). "Bicyclo[1.1.0]butane". Org. Synth. 51: 55. doi:10.15227/orgsyn.051.0055.; Coll. Vol., 6, p. 133
  22. ^ Kochi, J. K. (1965). "A New Method for Halodecarboxylation of Acids Using Lead(IV) Acetate". Journal of the American Chemical Society. 87 (11): 2500–2502. doi:10.1021/ja01089a041.

External linksEdit