Acylation Perkin reaction

A variant of the Perkin reaction is the Erlenmeyer-Plochl-azlactone synthesis By condensation of an aromatic aldehyde 1 with an N-acyl glycine 5 in the presence of sodium acetate and acetic anhydride, an azlactone 6 is obtained via the following mechanism ... 

G. M. Blackburn, J. D. Plackett, Strain Effects in Acyl Transfer Reactions. Part I. The Kinetics of Hydrolysis of Some N-Aryl-Lactams , J. Chem. Soc., Perkin Trans. 2 1972, 1366-1371. 

In the laboratory of D. Ma, the asymmetric synthesis of several metabotropic glutamate receptor antagonists derived from a-alkylated phenylglycines was undertaken. The preparation of (S)-1-aminoindan-1,5-dicarboxylic acid (AIDA) started with the Perkin reaction of 3-bromobenzaldehyde and malonic acid. The resulting ( )-cinnamic acid derivative was hydrogenated and the following intramolecular Friedel-Crafts acylation afforded the corresponding indanone, which was then converted to (S)-AIDA. 

The generally accepted mechanism for the Perkin reaction is shown in Scheme 2. Much of the early woik leading to this view, which was the result of numerous investigations spanning a period of greater than SO years, has been reviewed in some detail. Formation of the anhydride enolate (1) and aldol-type condensation generates the alkoxide anhydride (2). Intramolecular acylation provides an acetoxycaibox-ylate (3), which forms a mixed anhydride elimination of acetic acid and hydrolysis affords the unsatu-... 

The Perkin reaction is believed to proceed by forming an enolate anion 5 from the acid anhydride 2, which subsequently reacts with the aldehyde 1 to form an alkoxide 6. The ensuing intramolecular acylation affords P-acyloxy derivative 8, which undergoes... 

A variation of this condensation involves reaction with aldehydes, and it is called the Perkin reaction. Condensation of an aldehyde (having no enolizable protons) with the enolate of an acid anhydride leads to an acetoxy ester such as 182.10 Internal acyl substitution by the alkoxide forms the 0-acetyl ester and liberates the carboxylate anion (183). Subsequent reaction with more acetic anhydride generates a new mixed... 

Polymeric amines can be proton acceptors, acyl transfer agents, or ligands for metal ions. The 2- and 4-isomers of poly(vinylpyridine) (11) and (12) and the weakly basic ion exchange resins, p-dimethylaminomethylated PS (2) and poly(2-dimethylaminoethyl acrylate), are commercial. The ion exchange resins are catalysts for aldol condensations, Knoevenagel condensations, Perkin reactions, cyanohydrin formation and redistributions of chlorosilanes. " The poly(vinylpyridine)s have been used in stoichiometric amounts for preparation of esters from acid chlorides and alcohols, and for preparation of trimethylsilyl ethers and trimethylsilylamines from chlorotrimethylsilane and alcohols or amines. Polymer-suppored DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (52) in stoichiometric amounts promotes dehydrohalogenation of alkyl bromides and esterification of carboxylic acids with alkyl halides. The protonated tertiary amine resins are converted to free base form by treatment with aqueous sodium hydroxide. 

In mainstream organic synthesis acetylation is usually accomplished using acetic anhydride rather than the more reactive acetyl chloride. However, acetic anhydride has been much less used in carbon-14 synthesis because of the unavoidable loss of 50% of the radioactivity. Therefore, its use is limited to the labeling of substrates that have to be acylated either under very mild conditions or in very small quantities (e.g. proteins ), or to Perkin reactions, where its active methylene group is involved. 

As data for the rates of spin-trapping reactions are accumulated, so it becomes possible to use the competition experiment in reverse , i.e. to determine rates of rearrangement, fragmentation, atom transfer, etc. which can compete with spin trapping. An attempt to estimate rates of decarbonylation of acyl radicals depended on this approach (Perkins and Roberts, 1973). Although the results obtained were intuitively reasonable, they depended on the assumption that the rate of scavenging of acyl radicals by MNP would be no different from that measured for the butoxycarbonyl radical. This still awaits experimental verification. Another application, reported recently, was to the rates of rearrangement (23) of a series of (o-(alkoxycarbonyl)-alkyl radicals... 

The Perkin synthesis of cinnamic acids is considered to involve reaction of the enolate anion derived from the acid anhydride with the aldehyde, giving rise to the alkoxide (391). Intramolecular acylation follows and the resulting /3-acyloxy derivative undergoes elimination to the unsaturated acid (Scheme 125). 

Harkin, S.A., Singh, O., and Thomas, E.J., Approaches to cytochalasan synthesis. Preparation and Diels-Alder reactions of 3-alkyl- and 3-acyl-A -pyrrolin-2-ones, J. Chem. Soc., Perkin Trans. 1, 1489, 1984. 

K. Bock, C. Pedersen, and P. Rasmussen, Reactions of acylated pentoses and acylated methyl pentosides with dibromomethyl methyl ether. Preparation of bromo-deoxy-pentoses, J. Chem. Soc., Perkin I, (1973) 1456-1461. 

Gripenberg in The Chemistry ofFlavonoid Compounds, Geissman, Ed. (New York, 1962) p 410. Mechanistic studies K. Bowden, M. Chehel-Amiran, J. Chem. Soc. Perkin Trans. II 1986, 2039. Synthetic applications P. K. Jain etal, Synthesis 1982, 221 J. Zhu etal., Chem. Commun. 1988,1549 A. V. Kalinin et al, Tetrahedron Letters 39,4995 (1998) D. C. G. Pinto et al, New J. Chem. 24, 85 (2000). Cf. Allan-Robinson Reaction Kostanecki Acylation. 

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