The Dakin–West reaction is a
chemical reaction
A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...
that transforms an
amino-acid into a
keto-
amide using an
acid anhydride and a base, typically
pyridine. It is named for
Henry Drysdale Dakin and Randolph West. 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 (from the Latin language, Latin ''wikt:solvo#Latin, solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a Solution (chemistry), solution. A solvent is usually a liquid but can also be a solid, a gas ...
, 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.
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; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...
-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.''
See also
*
Robinson–Gabriel synthesis - A process for converting the keto-amide products of this reaction into
oxazoles
References
{{Organic reactions
Carbon-carbon bond forming reactions
Substitution reactions
Name reactions