Cinnamic acid anhydride

An acyl transfer agent which can be used for the synthesis of acid anhydrides is obtained from the reaction of an acid chloride with 4-benzylpyridine (equation 24). In this way benzoic acid anhydride and cinnamic acid anhydride were obtained in 72% and 57% yields, respectively. As the intermediate, 1-acyl-4-benzylidene-l,4-dihydropyridines, can be isolated, Ais procedure should be well suited for the preparation of mixed anhydrides. Mixed aromatic and aliphatic anhydrides can be prepared with 2-ben-zoylthio-l-methylpyridinium chloride and salts of carboxylic acids. These reactions are carried out in aqueous solution. Iliey make use of the high reactivity of esters of thiocarboxylic esters towards nucleophiles. The mixed anhydrides of benzoic acid with 3-phenylpropanoic acid, phenoxyacetic acid, isobu-tyric acid, p-toluic acid and cinnamic acid were formed in 82, 79,61,91 and 66% yields, respectively. 

Similarly cinnamic acid anhydride is formed from phenylcyclopropenone when it is kept in air [91]. 

Its chief importance is as a source of cinnamic acid by condensation with sodium ethan-oate and ethanoic anhydride and as a source of triphenylmethane dyestuffs by condensation with pyrogallol, dimethylaniline, etc. It is also used in the manufacture of perfumes. 

In general, condensation takes place at the a-carbon atom, leading to simple cinnamic acids or to their a-substituted derivatives. When possible, the anhydride corresponding to the sodium sail should be the condensing agent. 

Cinnamic acid is usually prepared by Perkin s reaction, benzaldehyde being heated with sodium acetate in the presence of acetic anhydride. It is probable that the benzaldehyde and the acetic anhydride combine under the catalytic action of the sodium acetate, and the product then readily loses water to give mono-benzylidene acetic anhydride (. ). The latter, when subsequently... 

Coumarin is usually prepared by heating salicylaldehyde with acetic anhydride and sodium acetate (i.e., the Perkin cinnamic acid synthesis, p. 23 6), whereby the 0" hydroxy-cinnamic acid (I) undergoes cyclisation to coumarin. Coumarins having substituents in the benzene ring can often be similarly prepared. 

Furfural condenses with acetic anhydride and potassiuiu acetate to give furylacrylic acid (compare Perkin reaction, Cinnamic Acid, Section IV, 124) ... 

Reactions. Heating an aqueous solution of malonic acid above 70°C results in its decomposition to acetic acid and carbon dioxide. Malonic acid is a useful tool for synthesizing a-unsaturated carboxyUc acids because of its abiUty to undergo decarboxylation and condensation with aldehydes or ketones at the methylene group. Cinnamic acids are formed from the reaction of malonic acid and benzaldehyde derivatives (1). If aUphatic aldehydes are used acryhc acids result (2). Similarly this facile decarboxylation combined with the condensation with an activated double bond yields a-substituted acetic acid derivatives. For example, 4-thiazohdine acetic acids (2) are readily prepared from 2,5-dihydro-l,3-thiazoles (3). A further feature of malonic acid is that it does not form an anhydride when heated with phosphorous pentoxide [1314-56-3] but rather carbon suboxide [504-64-3] [0=C=C=0], a toxic gas that reacts with water to reform malonic acid. 

Manufacture. The most widely employed method for the commercial synthesis of (H)-cinnamic acid uti1i2es ben2aldehyde, acetic anhydride, and anhydrous sodium or potassium acetate in a condensation reaction commonly referred to as the Perkin reaction (11). 

The cinnamic acid is readily prepared by heating benzaldehyde with acetic anhydride and sodium acetate (the Perkin Reaction) (Figure 16.2). 

The mi.xtuie of benzaldehyde, sodium acetate, and acetic anhydride is heated to 180 m a sir.all round flask with upright condenser in an oil-bath for about eight houis. The mass is poured out whilst hot into a large round flask (i litre), sodium carbonate added until alkaline, and any unchanged benzaldehyde distilled off with steam. After filtering from undissolved resinous by-products, hydrochloric acid is added, which precipitates the free cinnamic acid in white crystalline flakes. It may be purified by recrystallisation from hot water. Yield, 15—20 grams. 

The aldol-like reaction of an aromatic aldehyde 1 with a carboxylic anhydride 2 is referred to as the Perkin reaction. As with the related Knoevenagel reaction, an o ,/3-unsaturated carboxylic acid is obtained as product the /3-aryl derivatives 3 are also known as cinnamic acids. 

Benzaldehyde Acetic anhydride Cinnamic acid Acetic acid... 

In this reaction the carbanion (103) is obtained by removal of an ot-H atom from a molecule of an acid anhydride (104), the anion of the corresponding acid acting as the necessary base the carbonyl acceptor is pretty well confined to aromatic aldehydes. The products are a/J-unsaturated acids, e.g. 3-phenylpropenoic(cinnamic) acid (105) from PhCHO/excess (MeC0)20/MeC02e at 140° ... 

A. 0.02 M substituted benzaldehyde, 27 g acetic anhydride, 12 g fused K acetate in 250 ml round bottom flask with air condenser and CaCI2 tube. Heat on oil bath at 160° one hour and then at 175c for four hours. Pour into water (neutralize with Na carbonate and steam distill to recover unreacted aldehyde), cool, acidify and filter to get about 60% yield substituted cinnamic acid (I). 

Cinnamic Acid from Benzaldehyde and Acetic Anhydride... 

Phenyl cinnamate and other phenolic esters have been prepared by heating the acid and phenol in the presence of phosphorus oxychloride,1 and by heating the acid anhydride and phenol together in the presence of a dehydrating agent such as fused zinc chloride or anhydrous sodium acetate.2 Phenyl cinnamate has also been prepared by the careful distillation of phenyl fumarate.3... 

Cinnamic acid synthesis from aryl aldehyde and acetic anhydride. 

When benzaldehyde is condensed with hippuric acid in the presence of acetic anhydride a Perkin s reaction takes place and benzoyl-a-amido-cinnamic acid is formed —... 

Hydrogenation of benzaldehyde yields benzyl alcohol, condensation with aliphatic aldehydes leads to additional fragrance substances or their unsaturated intermediates. Unsaturated araliphatic acids are obtained through the Perkin reaction, for example, the reaction with acetic anhydride to give cinnamic acid. 

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). 

Further support for the intermolecular route is provided by the isolation of the substituted trans-cinnamic acid, the normal Perkin product. This arises through elimination of carboxylic acid from the fully acylated species (393) rather than cyclization. For example, a considerable amount of 2-acetoxy-3-methoxycinnamic acid is formed from 3-methoxysalicylaldehyde, perhaps as a result of steric interference with cyclization so allowing the intermolecular process to predominate (39JPR(152)23). It should be noted that trans- 2-hydroxycinnamic acids do not cyclize under normal Perkin conditions, though the cis isomer does so quite readily. Isomerization of the trans acid has been effected by treatment with a trace of iodine in acetic anhydride or by UV irradiation. 

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