Dakin–West reaction
{{Short description|Reaction that converts amino acids into a keto-amides}}
{{dist|Dakin reaction}}
The Dakin–West reaction is a chemical reaction that transforms an amino-acid into a keto-amide using an acid anhydride and a base, typically pyridine.{{cite journal|last1=Dakin|first1=Henry Drysdale|last2=West|first2=Randolph|title=A General Reaction of Amino Acids|journal=The Journal of Biological Chemistry|date=1928|volume=78|issue=1|pages=91–104|doi=10.1016/S0021-9258(18)84021-2|doi-access=free}}{{cite journal|last1=Dakin|first1=Henry Drysdale|last2=West|first2=Randolph|title=A General Reaction of Amino Acids. II|journal=The Journal of Biological Chemistry|date=1928|volume=78|issue=3|pages=745–756|doi=10.1016/S0021-9258(18)83978-3|doi-access=free}}{{cite journal|last1=Dakin|first1=Henry Drysdale|last2=West|first2=Randolph|title=Some Aromatic Derivatives of Substituted Acetylaminoacetones|journal=The Journal of Biological Chemistry|date=1928|volume=78|issue=3|pages=757–764|doi=10.1016/S0021-9258(18)83979-5|doi-access=free}}{{cite journal|last1=Wiley|first1=Richard H.|title=The Conversion of Amino Acids to Oxazoles|journal=The Journal of Organic Chemistry|date=1947|volume=12|issue=1|pages=43–46|doi=10.1021/jo01165a006|pmid=20280736}}{{cite journal|last1=Buchanan|first1=G. L.|title=The Dakin–West reaction|journal=Chemical Society Reviews|date=1988|volume=17|pages=91–109|doi=10.1039/CS9881700091}} 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.{{cite journal|last1=Wende|first1=Raffael C.|last2=Seitz|first2=Alexander|last3=Niedek|first3=Dominik|last4=Schuler|first4=Sören M. M.|last5=Hofmann|first5=Christine|last6=Becker|first6=Jonathan|last7=Schreiner|first7=Peter R.|title=The Enantioselective Dakin-West Reaction|journal=Angewandte Chemie International Edition|date=2016|volume=55|issue=8|pages=2719–2723|doi=10.1002/anie.201509863|pmid=26804727}}
Image:Dakin-West Reaction Scheme.png
With pyridine as a base and solvent, refluxing conditions are required.{{cite journal|last1=Wiley|first1=Richard H.|last2=Borum|first2=O. H.|title=3-Acetamido-2-butanone|journal=Organic Syntheses|date=1953|volume=33|page=1|doi=10.15227/orgsyn.033.0001}} However, with the addition of 4-dimethylaminopyridine (DMAP) as a catalyst, the reaction can take place at room temperature.{{cite journal|last1=Höfle|first1=Gerhard|last2=Steglich|first2=Wolfgang|last3=Vorbrüggen|first3=Helmut|title=4-Dialkylaminopyridines as Highly Active Acylation Catalysts. [New synthetic method (25)]|journal=Angewandte Chemie International Edition in English|date=1978|volume=17|issue=8|pages=569–583|doi=10.1002/anie.197805691}}
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 bond. Subsequent ring-opening of 6 and decarboxylation give the final keto-amide product.{{cite journal|last1=Knorr|first1=Rudolf|last2=Huisgen|first2=Rolf|title=Zum Mechanismus der Dakin-West-Reaktion, I Die Reaktion von N-Acyl-sek.-aminosäuren mit Acetanhydrid|journal=Chemische Berichte|date=1970|volume=103|issue=8|pages=2598–2610|doi=10.1002/cber.19701030831|pmid=5448834}}{{cite journal|last1=Allinger|first1=Norman L.|last2=Wang|first2=Grace L.|last3=Dewhurst|first3=Brian B.|title=Kinetic and mechanistic studies of the Dakin-West reaction|journal=The Journal of Organic Chemistry|date=1974|volume=39|issue=12|pages=1730–1735|doi=10.1021/jo00925a029}}
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.{{cite journal|last1=Tran|first1=Khanh-Van|last2=Bickar|first2=David|title=Dakin−West Synthesis of β-Aryl Ketones|journal=The Journal of Organic Chemistry|date=2006|volume=71|issue=17|pages=6640–6643|doi=10.1021/jo0607966|pmid=16901161}}
See also
- Robinson–Gabriel synthesis - A process for converting the keto-amide products of this reaction into oxazoles
References
{{reflist}}
{{Organic reactions}}
Category:Carbon-carbon bond forming reactions