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.[2][3] A catalytic approach has been developed.[4]
Hunsdiecker reaction | |
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Named after | Heinz Hunsdiecker Cläre Hunsdiecker Alexander Borodin |
Reaction type | Substitution reaction |
Identifiers | |
Organic Chemistry Portal | hunsdiecker-reaction |
RSC ontology ID | RXNO:0000106 |
History
The reaction is named after Cläre Hunsdiecker and her husband Heinz Hunsdiecker, whose work in the 1930s[5][6] developed it into a general method.[1]The reaction was first demonstrated by Alexander Borodin in 1861 in his reports of the preparation of methyl bromide (CH3Br) from silver acetate (CH3CO2Ag).[7][8] 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.[2] 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.[9][10]
Using a 3:2 ratio of reactants leads to the formation of a 1:1 mixture of both products.[9][10] These processes are sometimes known as the Simonini reaction rather than as modifications of the Hunsdiecker reaction.[2][3]
- 3 RCOOAg + 2 I
2 → RI + RCOOR + 2 CO
2 + 3 AgI
Reaction mechanism
In terms of reaction mechanism, the Hunsdiecker reaction is believed to involve 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 > secondary > tertiary.[2][3]
Variations
The reaction cannot be performed in protic solvents, as these induce decomposition of the intermediate acetyl hypohalite.[citation needed]
Other counterions than silver typically have slow reaction rates. The toxic[11] relativistic metals (mercury, thallium, and lead) are preferred: inert counterions, such as the alkali metals, have only rarely led to reported success.[12]: 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.[13]
![](http://upload.wikimedia.org/wikipedia/commons/thumb/b/bf/Kochi_reaction.svg/250px-Kochi_reaction.svg.png)
In the presence of multiple bonds, 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).[12]: 468
Mercuric oxide and bromine convert 3-chlorocyclobutanecarboxylic acid to 1-bromo-3-chlorocyclobutane. This is known as Cristol-Firth modification.[14][15][16] The 1,3-dihalocyclobutanes were key precursors to propellanes.[17] 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.[18]
Reaction with α,β-unsaturated carboxylic acids
![](http://upload.wikimedia.org/wikipedia/commons/thumb/6/6c/Microwave-Induced_Hunsdiecker_Rxn_with_NXS.png/424px-Microwave-Induced_Hunsdiecker_Rxn_with_NXS.png)
For unsaturated conmpounds, the radical conditions associated with the Hunsdiecker reaction can also induce polymerization instead of decarboxylation.[12]: 468 Consequently, reactions with α,β-unsaturated carboxylic acids typically give low yield.[11] 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 irradiation, which preferentially synthesizes (E)-β-arylvinyl halides.[19]
For a green metal-free reaction, tetrabutylammonium trifluoroacetate serves as an alternative catalyst.[20] However, it only exhibits comparable yields to the original lithium acetate when performed with micellular surfactants.[19][21][22]