Perkin reaction mechanisms

Kinastowski, S., Kasprzyk, H., Grabarkiewicz, J. Perkin reaction mechanism. Bulletin de TAcademie Polonaise des Sciences, Serie des Sciences Chimiques 1975, 23, 211-214. 

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 ... 

This reaction type leading to oc,/ -unsaturated acids and esters is exemplified in the Perkin reaction (Section 6.12.3, p. 1036) and the Knoevenagel reaction (Section 5.11.6, p. 681). The Doebner reaction, which is illustrated in this section, is the condensation of an aldehyde with malonic acid in pyridine solution, often in the presence of a trace of piperidine. The reaction mechanism involves the addition of a malonate anion to the aldehydic carbonyl carbon atom followed by the elimination of water accompanied by decarboxylation. 

A. K. Butler and M. J. Perkins (Eds.), Organic Reaction Mechanism, Wiley, London, 1975. 

Classically, this separation of roles was accomplished by utilizing substrates that differed drastically in their ability to form enolate anions. In fact, the various name reactions mentioned above are distinguished not by basic differences in mechanism, but by the nature of the components preferentially utilized as substrates. For example, in the Perkin reaction, the condensation of an aromatic aldehyde with an aliphatic acid anhydride is based on the fact that the electrophilic component, e.g. benzaldehyde, lacks a-hydrogens and therefore is incapable of forming an enolate. At the same time the utilized electrophile, acetic anhydride, contains a carbonyl group with reduced propensity to interact with nucleophiles. Hence, it is incapable of undergoing self-condensa-... 

B. Capon, M. J. Perkins and C. W. Rees, Organic Reaction Mechanisms ig6s, Interscience, London, 1966, p, 104. 

Pohjala, E. Indolizine derivatives. IV. Evidence for a disproportionation-dehydrogenation mechanism in the Perkin reaction of 2-pyridinecarbaldehyde in the presence of a,P-unsaturated carbonyl compounds to give 1-acylpyrrolo[2,1,5-cd]indolizines. Heterocycles 1975,3, 615-618. 

Alonso, E., del Pozo, C., Gonzalez, J. Staudinger reactions of unsymmetrical cyclic ketenes a synthetically useful approach to spiro p-lactams and derivatives. Reaction mechanism and theoretical studies. J. Chem. Soc., Perkin Trans. 1 2002, 571-576. 

Perkin Reaction.9 When an aromatic aldehyde is heated with an hydride of the type (RCH2C0)20 and a salt of the corresponding acid, Substituted -arylacrylic acids are obtained. This reaction is usually called the Perkin reaction. Its mechanism may be outlined as follows ... 

Data taken from A.F. Hegarty P. Tuohey, Hydrolysis of Azo Esters via Azoformate Intermediates, J. Chem. Soc., Perkin Trans. 2. 1980, 1238 A. Williams, Free Energy Correlations and Reaction Mechanisms, in M. I. Page, ed., Chemistry of Enzyme Action, Elsevier, Amsterdam, 1984, p. 145. 

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-... 

Analogous results were reported earlier concerning the Perkin reaction of quinones. Treatment of 2,6-dimethoxy-p-benzoquinone with propionic anhydride in the presence of sodium propionate affords a mixture of condensation-derived products (12) and (13) (Scheme 6). However, when the reaction is carried out under milder conditions, among the products isolated is the 3 lactone (14). Compound (14) can be converted under Perkin conditions to (12) and (13). It is noted that (14) could be in equilibrium with dimethoxybenzoquinone and methylketene its isolation does not prove with certainty its intermediacy in the formation of (12) and (13). Thus, the actual mechanism of this condensation is not necessarily as simple as indicated in Scheme 2 and may involve more than one distinct pathway, depending on the exact nature of the particular substrate or base employed. 

Mechanism of Perkin reaction. The mechanism of the reaction, which is of the aldol-t3rpe may be expatiated with the help of the following equations (a) and (6) respectively. 

---