The Dakin–West reaction is a
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
that transforms an
amino-acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ami ...
into a
keto-
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...
using an
acid anhydride An acid anhydride is a type of chemical compound derived by the removal of water molecules from an acid.
In organic chemistry, organic acid anhydrides contain the functional group R(CO)O(CO)R'. Organic acid anhydrides often form when one equivale ...
and a base, typically
pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula . It is structurally related to benzene, with one methine group replaced by a nitrogen atom. It is a highly flammable, weakly alkaline, water-miscible liquid with a ...
. It is named for
Henry Drysdale Dakin
Henry Drysdale Dakin FRS (12 March 188010 February 1952) was an English chemist.
He was born in London as the youngest of 8 children to a family of steel merchants from Leeds. As a school boy, he conducted water analysis with the Leeds City Ana ...
(1880–1952) and Randolph West (1890–1949). In 2016 Schreiner and coworkers reported the first asymmetric variant of this reaction employing short oligopeptides as catalysts.
With pyridine as a base and
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
, refluxing conditions are required. However, with the addition of
4-dimethylaminopyridine (DMAP) as a catalyst, the reaction can take place at room temperature.
With some acids, this reaction can take place even in the absence of an α-amino group.
This reaction should not be confused with the
Dakin reaction
The Dakin oxidation (or Dakin reaction) is an organic redox reaction in which an '' ortho''- or ''para''-hydroxylated phenyl aldehyde (2-hydroxybenzaldehyde or 4-hydroxybenzaldehyde) or ketone reacts with hydrogen peroxide in base to form a ...
.
Reaction mechanism
The reaction mechanism involves the acylation and activation of the acid 1 to the mixed anhydride 3. The amide will serve as a nucleophile for the cyclization forming the
azlactone 4. Deprotonation and acylation of the azlactone forms the key
carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...
-carbon bond. Subsequent ring-opening of 6 and
decarboxylation give the final keto-amide product.
General ketone synthesis
Modern variations on the Dakin–West reaction permit many enolizable carboxylic acids – not merely amino acids – to be converted to their corresponding methyl ketones. For example, β-aryl carboxylic acids can be efficiently converted to β-aryl ketones by treatment of an
acetic anhydride solution of the acid with catalytic
N-methylimidazole. This reactivity is attributed in part to generation of acetylimidazolium, a powerful cationic acetylating agent, ''
in situ
''In situ'' (; often not italicized in English) is a Latin phrase that translates literally to "on site" or "in position." It can mean "locally", "on site", "on the premises", or "in place" to describe where an event takes place and is used in ...
.''
See also
*
Robinson–Gabriel synthesis
The Robinson–Gabriel synthesis is an organic reaction in which a 2-acylamino-ketone reacts intramolecularly followed by a dehydration to give an oxazole. A cyclodehydrating agent is needed to catalyze the reaction It is named after Sir Robert Ro ...
- A process for converting the keto-amide products of this reaction into
oxazoles
References
{{DEFAULTSORT:Dakin-West Reaction
Carbon-carbon bond forming reactions
Substitution reactions
Name reactions