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.^[2][3] A catalytic approach has been developed.^[4]

History[edit]

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[edit]

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[edit]

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

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.^[13][14][15] The 1,3-dihalocyclobutanes were key precursors to propellanes.^[16] 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.^[17]

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.^[18]

Reaction with α,β-unsaturated carboxylic acids[edit]

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]

See also[edit]

• Barton decarboxylation
• Barton–McCombie deoxygenation

References[edit]

External links[edit]

• Animation of the reaction mechanism