Condensation Perkin

Introduction of the two-carbon fragment is a cornerstone of synthetic methodology and many of the condensation reactions frequently used have been known for decades, if not for a century. Examples include the malonic ester and acetoacetic ester reactions, the Perkin condensation, and the Doebner-... 

Perkin condensation is the reaction between aromatic aldehydes and aliphatic acid anhydrides (in the presence of the sodium salt) to form p-arylacrylic acid... 

Condensation between anhydrides and aldehydes (Perkin) Condensation between P-carboxy phosphoranes and aldehydes or ketones... 

Cohare and co-workers reported that aristolactam BU (22) was prepared, following Kupchen s method, by Perkin condensation of 6-bromo-3,4-di-methoxy phenyl acetic acid (119) and o-nitrobenzaldehyde (120) (Scheme 14). The 2-bromo-4,5-dimethoxy-2 -nitro-ds-stilbene-a-carboxylic acid (121) was obtained. The nitro group of 121 was reduced with ferrous sulfate and ammonium hydroxide, and the resulting 2-bromo-4,5-dimethoxy-2 -amino-cw-stilbene-a-carboxylic acid (122) without purification was submitted to the Pschorr phenanthrene synthesis to yield l-bromo-3,4-dimethoxyphen-anthrene-lO-carboxylic acid (123). The phenanthrylamine 124 was prepared from 123 via a Schmidt reaction, and, by treatment with n-butyllithium and CO2, 124, afforded 22 (42). 

One of the original routes into [18]annulenes (e.g. 44) possessing heterocyclic rings utilized the Perkin condensation (acetic anhydride-triethylamine). This cyclocondensation procedure transformed (45) and (46) into (44) in low yield the overall results have been reviewed (77CRV513). 

Problem 17.36 Prepare /rarw-cinnamic acid, C H,CH=CHCOOH, by a Perkin condensation [Problem 17.34(a)], ... 

Cyclization of 3-methylenethio-l-oxopropyl derivatives (Perkin condensations) 873... 

Similar in style to the above are the base-catalyzed intramolecular cyclizations of diesters (116) and substituted salicylaldehydes (117), Dieckmann and Perkin condensations, respectively (36JCS212, 36JCS419, 40JCS787). 

The anhydride also undergoes a Perkin condensation with aromatic aldehydes in the presence of a base to give l-oxo-3-phenylisochroman-4-carboxylic acids (58JCS2612). 

The mechanism of the Perkin condensation involving benzal acetate has been revised.17 It has been demonstrated that the enolate of the gem-diacetate derived from the aromatic aldehyde and acetic anhydride-rather than the enolate of acetic anhydride itself-adds to the aldehyde in the key step. The deprotonation of the diacetate to the enolate appeared to be assisted electrophilically by the neighbouring acetate group. 

The base-catalyzed reaction of an aldehyde (having no a hydrogens) with an anhydride is called the Perkin condensation. Propose a mechanism for the following example of the Perkin condensation. (Sodium acetate serves as the base.)... 

Paraconic acids, pyrolysis, 54 Perkin condensation, 52 Phenolic aldehydes, preparation, 281, 282... 

Perkin condensation. 392 Peroxides in ethers, 284 Phase transfer catalyst, 128 Phenanthrene, 198 Phenetole, 278, 431 Phenolphthalein. 444 Phenols, acidity of, 433 summary of chemistry. 441 Phenylhydrazine, 315 Phosgene, 4, 369 Phthalic acid, 343 Phthalimide. 403 Pi bond, 15 Picoline, 454, 457 Picric acid, 432... 

The cinnamic acid obtained by the Perkin condensation is the more stable trans-isomer, Suggest a method of preparing c/.y-cinnamic acid. (Hint See Sec. 8.9.)... 

There are several general ways to make compounds of this kind the aidol condensation, to make unsaturated aldehydes and ketones dehydrohalogenation of a-halo acids and the Perkin condensation, to make unsaturated acids. Besides these, there are certain methods useful only for making single compounds. 

The large-scale pilot plant preparation of the chiral aminochroman antidepressant ebaizotan (also known as NAE-086) was developed by H.J. Federsel and co-workers. The structural features of the target included a disubstituted chroman skeleton, a stereocenter, as well as a non-symmetrical tertiary amine moiety at the C3 position and a secondary carboxamide group at C5. The backbone of the target molecule was constructed using the Perkin condensation of 2-hydroxy-6-methoxybenzaldehyde with hippuric acid under mild conditions. 

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