Preparation Perkin condensation

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). 

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

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

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.)... 

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. 

Thiele and Schleussner prepared ira/ii,franj-l,4-diphenylbutadiene by reaction of cinnamaldehyde with sodium phenylacetate and acetic anhydride at a temperature such that the initially formed product of Perkin condensation loses carbon dioxide. Kuhn and Winterstein employed lead oxide as the base and reported an increase in crude yield from 20 to 34%. The lower yield of 23-25% reported in Organic... 

An important variation of the Perkin reaction is the Erlenmeyer azalactone synthesis exemplified by equation (4), involving condensation of an aldehyde and an N-acylglycine derivative in the presence of acetic anhydride and sodium acetate. Although this reaction, analogous to the classical Perkin condensation, was initially limited to the use of aromatic aldehydes, Baltazzi and Robinson reported that the use of lead acetate and THF allowed the preparation of several azalactones derived from aliphatic aldehydes (equation 15). The results for the condensation of several aldehydes and ketones with hippuric acid (28) under these conditions are shown in Table 2. The reaction proceeds through the intermediate (26) (intramolecular condensation of 25), which reacts with the aldehyde in Perkin fashion to provide the so-called azalactone product (Scheme 8). It is the formation of such oxazolones from acylamino acids which is be-... 

Indoxyls are normally prepared from anthraiiilic acids via alkylation with a haloacetic acid followed by a cyclising Perkin condensation. It is also possible to directly chloroacylate an aniline, ortho to the nitrogen. ... 

This reaction was first reported by Perkin in 1883. It is the nucleophilic alkylation between malonic ester and Q, o)-alkyl dihalide to form cyclic aliphatic 1,1-diester or acid and is known as the Perkin reaction or Perkin synthesis. Although it was once referred to as the Perkin condensation, this name should not be used for this type of reaction. Using this protocol, Perkin successfully prepared cyclopropane-, cyclobutane-, cyclopentane-, cyclohexane-, and cycloheptane-1,1-dicarboxylie acids. However, this reaction is often complicated by the side reaction that forms Q, o, a ,a -tetracarboxylic ester from the Sn2 reaction between malonic ester and o, a -alkyl dihalide, this side reaction can be depressed if alcoholic sodium malonic ester is added slowly to the o, a -alkyl dihalide with vigorous stirring. It is interesting that the K2CO3 promoted a reaction between dimethyl 1,3-acetonedicarboxylate and tran5 -l,4-dibromobutene yields vinyldihydrofuran. ... 

The Perkin condensation is an aldol-type condensation in which an aromatic aldehyde (ArCHO) reacts with a carboxyUc acid anhydride, (RCH2C0)20, to give an a,j8-unsaturated acid (ArCH = CRCO2H). The catalyst that is usually employed is the potassium salt of the carboxylic acid (RCH2CO2K). (a) Outline the Perkin condensation that takes place when benzaldehyde reacts with propanoic anhydride in the presence of potassium propanoate. (b) How would you use a Perkin condensation to prepare />-chlorocinnamic acid, />-CIC6H4CH = CHC02H ... 

Here the phenylacetic anhydride, possessing more reactive a-hydrogen atoms, condenses with benzaldehyde to give a-phenylcinnamic acid. The preparation of the latter is an example of the Oglialoro modiflcation of the Perkin reaction. 

Because of the mild reaction conditions, and its broad applicability, the Knoevenagel reaction is an important method for the synthesis of a ,/3-unsaturated carboxylic acids. Comparable methods are the Reformatsky reaction, the Perkin reaction, as well as the Claisen ester condensation. The Knoevenagel reaction is of greater versatility however the Reformatsky reaction permits the preparation of a ,/3-unsaturated carboxylic acids that are branched in a-position. 

David, S. and Lepine, M.-C., Preparation of sugars with branched chains, a methylene bridge, or C-l-phenyl substituents by the Ramirez dioxaphosphole condensation, /. Chem. Soc., Perkin l, 1262, 1980. 

The acid has been prepared through the Perkin reaction,1 by the condensation of furfural with malonic acid in the presence of pyridine,2 and, on a large scale, by the modified Perkin procedure of Johnson.3... 

Reaction xxklll. (d) Condensation of Aldehydes with the Sodium Salts of certain Adds in the presence of Add Anhydrides (Perkin). (A., 100,126 227, 48 B., 10,68 14,1826 J. C. S., 21, 53 J 1877, 789.) —This is a reaction of very wide application, and one much used in the preparation of unsaturated aromatic carboxylic acids. It consists in heating together—usually to 180°—an aldehyde, the sodium salt of a fatty acid with at least one oc-hydrogen atom, and an acid anhydride. The following reactions then occur —... 

Diphenylocta-1,3,5,7-tetraene can be prepared (Expt 6.140) by condensing two mols of cinnamaldehyde with succinic acid in the presence of acetic anhydride and lead oxide, in a reaction which bears similarities with those of the Perkin type discussed above. 

There are different methods of the synthetic preparation of acronycine (W. M. Bandaranayake et al., J. Chem. Soc. Perkin 1, 998 (1968) J. Hlubucek et al. Aust. J. Chem. 23, 1881 (1970). One of them is described below. Friedel-Crafts condensation between 2-nitrobenzoyl chloride and 3,5-dimethoxyphenol. 

The condensation product of dithiooxamide with benzaldehyde has been shown to be 2,5-diphenylthiazolo[5,4-d]thiazole (equation 75) (60JA2719). Its formation involves dehydration of the reactants and further dehydrogenation. The reaction is comparable in scope with condensations such as the Perkin reaction, and many 2,5-diarylthiazolo[5,4-c ]thiazoles have been prepared from a variety of aryl aldehydes. Condensation products were not obtained from simple aliphatic aldehydes (71JMC743). 

Infrared Spectra.—A gas-tight Kel-F cell fitted with AgCl windows was used for all condensed-phase spectra. The powdered solids were dusted on to the inner surfaces of the windows, the same precautions being taken as for X-ray sample preparation. A Perkin-Elmer 137 Infracord was used over its full range of 4000-400 cm". ... 

The Perkin reaction involves the condensation of a carboxylic acid anhydride and an aldehyde in the presence of a weak base, often the sodium or potassium salt of the acid or triethylamine, to give unsaturated carboxylic acids (equation 1). The first example of this reaction was described by Perkin in 1868 and involves a synthesis of coumarin by heating the sodium salt of salicylaldehyde with acetic anhydride (equation 2). The reaction is generally applicable only to aromatic aldehydes and is particularly useful for the preparation of substituted cinnamic acids, as illustrated by equation (3). ... 

Related condensations involving the replacement of the anhydride component with succinic acid (Fit-tig synthesis) or with malonic acid (Knoevenagel condensation, see Volume 2, Qiapter 1.11) provide complementary preparative methods which are useful for both aromatic and aliphatic systems. The Fittig extension of the Perkin transformation involves heating an aliphatic or aromatic aldehyde with sodium succinate and acetic anhydride to give the condensation products (17), which lose carbon dioxide to afford p,7-unsaturated cartoxylic acids (18), accompanied by small amounts of the corresponding 7-buty-rolactones (19 Scheme 7)P... 

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