Barton decarboxylation
Encyclopedia
The Barton decarboxylation is a radical reaction in which a carboxylic acid
is first converted to a thiohydroxamate ester (commonly referred to as a Barton ester). The product is then heated in the presence of a radical initiator
and a suitable hydrogen donor to complete the reductive decarboxylation
of the initial carboxylic acid. Using this reaction it is possible to remove a carboxylic acid moiety from an alkyl group and replace it with other functional groups. (See Scheme 1) This reaction is named after its developer, the British chemist and Nobel Prize laureate Sir Derek Barton
(1918–1998).
to form a carboxyl radical which then undergoes decarboxylation and carbon dioxide (CO2) is lost. The remaining alkyl radical (R·) then abstracts a hydrogen atom from remaining tri-n-butyltin hydride to form the reduced alkane (RH). (See Scheme 2) The tributyltin radical enters into another cycle of the reaction until all thiohydroxamate ester is consumed.
N-O bond cleavage of the Barton ester can also occur spontaneously upon heating or by irradiation with light to initiate the reaction. In this case a radical initiator is not required but a hydrogen-atom (H-atom) donor is still necessary to form the reduced alkane (RH). Alternative H-atom donors to tri-n-butyltin hydride include tertiary thiols and organosilanes. The relative expense, smell, and toxicity associated with tin, thiol or silane reagents can be avoided by carrying the reaction out using chloroform
as both solvent and H-atom donor.
It is also possible to functionalize the alkyl radical by use of other radical trapping species (X-Y + R· -> R-X + Y·). The reaction proceeds due to the formation of the stable S-Sn bond and aromatization of the thiohydroxamate ester. There is also an overall increase in entropy due to the formation of 3 products from 2 substrates which drives the reaction forward.
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
is first converted to a thiohydroxamate ester (commonly referred to as a Barton ester). The product is then heated in the presence of a radical initiator
Radical initiator
In chemistry, radical initiators are substances that can produce radical species under mild conditions and promote radical reactions . These substances generally possess weak bonds—bonds that have small bond dissociation energies. Radical initiators are utilized in industrial processes such...
and a suitable hydrogen donor to complete the reductive decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
of the initial carboxylic acid. Using this reaction it is possible to remove a carboxylic acid moiety from an alkyl group and replace it with other functional groups. (See Scheme 1) This reaction is named after its developer, the British chemist and Nobel Prize laureate Sir Derek Barton
Derek Harold Richard Barton
Sir Derek Harold Richard Barton FRS was a British organic chemist and Nobel Prize laureate.-Biography:Barton was born to William Thomas and Maude Henrietta Barton. He attended Tonbridge School and in 1938 he entered Imperial College London, where he graduated in 1940 and obtained his Ph.D. degree...
(1918–1998).
Mechanism
The reaction is initiated by homolytic cleavage of a radical initiator, in this case 2,2'-azobisisobutyronitrile (AIBN), upon heating. A hydrogen is then abstracted from tri-n-butyltin hydride to leave a tri-n-butyltin radical that attacks the sulfur atom of the thiohydroxamate ester. The N-O bond of the thiohydroxamate ester undergoes homolysisHomolysis
In general it means breakdown to equal pieces There are separate meanings for the word in chemistry and biology.-Homolysis in chemistry:...
to form a carboxyl radical which then undergoes decarboxylation and carbon dioxide (CO2) is lost. The remaining alkyl radical (R·) then abstracts a hydrogen atom from remaining tri-n-butyltin hydride to form the reduced alkane (RH). (See Scheme 2) The tributyltin radical enters into another cycle of the reaction until all thiohydroxamate ester is consumed.
N-O bond cleavage of the Barton ester can also occur spontaneously upon heating or by irradiation with light to initiate the reaction. In this case a radical initiator is not required but a hydrogen-atom (H-atom) donor is still necessary to form the reduced alkane (RH). Alternative H-atom donors to tri-n-butyltin hydride include tertiary thiols and organosilanes. The relative expense, smell, and toxicity associated with tin, thiol or silane reagents can be avoided by carrying the reaction out using chloroform
Chloroform
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
as both solvent and H-atom donor.
It is also possible to functionalize the alkyl radical by use of other radical trapping species (X-Y + R· -> R-X + Y·). The reaction proceeds due to the formation of the stable S-Sn bond and aromatization of the thiohydroxamate ester. There is also an overall increase in entropy due to the formation of 3 products from 2 substrates which drives the reaction forward.
See also
- Barton–McCombie deoxygenation
- Hunsdiecker reactionHunsdiecker reactionThe Hunsdiecker reaction is the organic reaction of silver salts of carboxylic acids with halogens to give organic halides. It is an example of a halogenation reaction...
- Kochi reactionKochi reactionThe Kochi reaction is an organic reaction for the decarboxylation of carboxylic acids to alkyl halides with lead tetraacetate and a lithium chloride or other lithium salts .The reaction is a variation of the Hunsdiecker reaction....
- Krapcho decarboxylationKrapcho decarboxylationThe Krapcho decarboxylation is the chemical reaction of esters with halide anions. The ester must contain an electron-withdrawing group in the beta position, such as β-ketoesters, malonic esters, α-cyanoesters, or α-sulfonylesters. It works best with methyl esters, since it is basically a...
- Kolbe electrolysisKolbe electrolysisKolbe electrolysis or Kolbe reaction is an organic reaction named after Adolph Wilhelm Hermann Kolbe. The Kolbe reaction is formally a decarboxylative dimerisation and proceeds by a radical reaction mechanism...
External links
- Barton Decarboxylation at organic-chemistry.org http://www.organic-chemistry.org/namedreactions/barton-decarboxylation.shtm
- Barton Decarboxylation at themerckindex.cambridgesoft.com https://themerckindex.cambridgesoft.com/TheMerckIndex/NameReactions/displayonr.asp?onr=ONR021.htm