By the Perkin reaction

Furylacrylic acid has usually been prepared from furfural by the Perkin reaction.1 The use of potassium acetate is advantageous, since it allows the reaction to proceed rapidly at relatively lower temperatures. The acid has also been prepared from furfural and malonic acid in the presence of pyridine,2 and by oxidation of furfuralacetone with bleaching powder.3... 

The cyclization giving maleic anhydride derivative 163 is also characterized by low yield. Moreover, the total yield of the starting dicyanide 162 was about 25% based on 2-methylbenzothiophene (90BCJ1311). This inefficiency was typical of most of the syntheses of photochromic maleic anhydrides from nitriles. Hence, the development of more efficient methods is a very important problem. Anhydride 163 has been synthesized recently (08JACS7286) by the Perkin reaction in good yields in each step (Scheme 50). 

Selenophene-2-aldehyde takes part in the Hantzsch synthesis [Eq. (I)]108 and reacts readily with ammonia, aromatic amines and diamines,109 hippuric, barbituric, and malonic acids, malononitrile,70 and rhodanine.109 /3-(Selenien-2-yl)acrylic acid has been obtained from selenophene-2-aldehyde by the Perkin reaction and by Knoevenagel condensation with malonic acid.70 Esters of /9-(selenien-2-yl)acrylic acid are easily formed by condensation of the aldehyde... 

Perkin Synthesis of Coumarin.—Coumaric acid and coumarin may be synthesized by the Perkin reaction for synthesizing unsaturated aromatic acids (p. 698). These syntheses are of historical interest as the two compounds obtained were the first onesprepared by this reaction. Instead of taking a simple aromatic aldehyde it is only necessary to take a phenol aldehyde viz., salicylic aldehyde,... 

Why potassium acetate is preferred over sodium acetate in carrying out the S3m-thesis of cinnamic acid by the Perkin Reaction ... 

Two isomers, namely, 3,5-dibenzylidenepyromellitide [12] and 3,7-dibenzylidenepyromellitide [13] were synthesized by the Perkin reaction of pyromellitic dianhydride and phenylacetlc acid in the presence of... 

Hrnciar, P., and L. Kuruc Phthalides and 1,3-Indandiones. XXVIII. Preparation of 5- and 6-Substituted 3-Benzalphthalides by the Perkin Reaction. Chem. Zvesti 21, 267 (1967). Chem. Abstr. 67, 73304v (1967). 

The Perkin reaction is of importance for the iadustrial production of coumarin and a number of modifications have been studied to improve it, such as addition of a trace of iodine (46) addition of oxides or salts of metals such as iron, nickel, manganese, or cobalt (47) addition of catalytic amounts of pyridine (48) or piperidine (49) replacement of sodium acetate by potassium carbonate (50,51) or by cesium acetate (52) and use of alkaU metal biacetate... 

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

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 ... 

As the chemical industry expanded, Perkin continued his own scientific research in the peace of his private laboratory. He had not lost his touch. Among the synthetic methods he discovered is one now called the Perkin reaction. He used it to make a synthetic substitute for a vegetable substance called coumarin, which has a pleasant, vanillalike odor. Coumarin spawned the synthetic perfume business and made luxurious scents available to all. Once again, a Perkin chemical started a new industry, albeit a modest one in comparison with dyes and pharmaceuticals. Despite the worldwide impact of Perkins discoveries, he was not knighted by the British monarchy until 1906, the fiftieth anniversary of his discovery of mauve. The world chemistry community feted him lavishly that year, and he traveled to the United States collecting further honors. A year later, at the age of 69, he died peacefully, at home. 

The Perkin reaction makes available Bz-alkyl Bz-hydroxyketones, which are difficult or impossible to obtain by other methods.799-801 It also applies in the field of furocoumarins 2-isopropylpsoralene (363), a... 

Benzo[6 jthiophenes with nitro groups at the 4-, 5-, 6- or 7-positions may be synthesized by ring closure reactions of appropriately substituted benzene derivatives. Nitration of 5-acetaminobenzo[6]thiophene gives the 4-nitro derivative, which can be hydrolyzed and deaminated to yield 4-nitrobenzo[6]thiophene (equation 44). 5-Nitrobenzo[6]thiophene is conveniently available by decarboxylation of 5-nitrobenzo[6]thiophene-2-carboxylic acid, which in turn is available by a Perkin reaction of 4-nitro-2-formylphenylthioglycoIic ester (equation 45 Section 3.15.2.3). The 7-nitro isomer may be obtained similarly. 

The strong conditions of the Perkin reaction may be circumvented by using phenylacetyl chloride in the presence of potassium carbonate in place of the anhydride in the preparation of 3-phenylcoumarins (81S887). However, 3-alkylcoumarins are not accessible in this way. 

Hydroxy benzo[6]thiophene-4-carboxaldehyde, which is prepared from 5-hydroxybenzo[6]thiophene by the Duff reaction 338 or, better, by a modified Gattermann reaction,340 reacts with diethyl bromo-malonate to give the thienobenzofuran (282), and undergoes the Perkin reaction to give the thienobenzo-a-pyrone (283).338... 

The forward synthetic reaction is a base-catalysed condensation reaction between two carbonyl compounds, the aldol condensation leading to -hydroxy-aldehydes or / -hydroxyketones followed by dehydration. This sequence is one of the most important carbon-carbon bond forming reactions, and aldol-type condensation reactions are considered in a number of other sections of the text, for example, the Doebner reaction (Section 5.18.3, p. 805), the Knoevenagel reaction (Section 5.11.6, p. 681), the Perkin reaction (Section 6.12.3, p. 1036) and the Robinson annelation reaction (Section 7.2). 

The reaction involves a spontaneous cyclisation of o-hydroxycinnamic acid obtained by a Perkin reaction using triethylamine as the base catalyst (Expt 6.138). 

Phenoxycoumarins. 3-Phenoxycoumarins have been obtained by a Perkin reaction of salicylaldehyde with the sodium salt of a substituted phenoxyacetic acid in... 

In the Perkin reaction, the carbanion is generated by abstraction of an a-hydrogen from an acid anhydride, with the anion of the corresponding acid acting as the base. For example, reaction of benzaldehyde with acetic anhydride in the presence of sodium acetate at high temperature yields 3-phenylpropenoic acid (Scheme 6.22). Although the mech-... 

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-... 

The Michael addition represents an extremely efficient synthetic method for achieving chain elongation by adding a three (or more) carbon fragment electrophile to a nucleophilic moiety. Notice that the typical Michael electrophiles (e.g. 90) are products of condensation of carbonyl compounds and can be easily formed via the aldol-like condensation, the Wittig reaction (with ylides like 81), the Perkin reaction, or the Mannich reaction (see below). 

The reaction of benzaldehyde with phenylacetic acid to produce a mixture of the a-carboxylic acid derivatives of Z- and -stilbene a form of aldol condensation known as the Perkin reaction, is effected by heating a mixture of the components with acetic anhydride and triethylamine. In the course of the reaction the phenylacetic acid is probably present both as anion and as the mixed anhydride resulting from equilibration with acetic anhydride. A reflux period of 5 h specified in an early procedure has been shortened by a factor of 10 by restriction of the amount of the volatile acetic anhydride, use of an excess of the less expensive, high-boiling aldehyde component, and use of a condenser that permits some evaporation and consequent elevation of the reflux temperature. 

In the Perkin reaction, acetic anhydride condenses with an aromatic aldehyde to yield a cinnamic acid. The reaction takes place by a mixed carbonyl condensation of the anhydride with the aldehyde to yield an a,/l-unsaturated intermediate that undergoes hydrolysis to yield the cinnamic acid. What is the structure of the unsaturated intermediate ... 

The combretastatins are a group of antimitotic agents isolated from the bark of the South African tree Combretum caffrum. A novel and highly stereoselective total synthesis of both the c/s and trans isomers of combretastatin A-4 was developed by J.A. Hadfield and co-workers.The (Z)-stereoisomer was prepared using the Perkin reaction as the key step in which 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxbenzaldehyde was heated with triethylamine and acetic anhydride at reflux for several hours. The a,p-unsaturated acid was isolated in good yield after acidification and had the expected ( ) stereochemistry. Decarboxylation of this acid was effected by heating it with copper powder in quinoline to afford the natural product (Z)-combretastatin A-4. 

Kinastowski, S., Kasprzyk, H. Ketene intermediates in the Perkin reaction catalyzed by tertiary amines. Bulletin de TAcademie Polonaise des Sciences, Serie des Sciences Chimiques 1978, 26, 907-915. 

An anion may be formed from a symmetrical acid anhydride by using the carboxylate anion of the corresponding acid as the base. This anion may then be reacted with an aldehyde, such as benzaldehyde, to yield as the initial product a mixed anhydride. Dehydration and hydrolysis often follow to result in an a, P-un saturated acid. This is the Perkin reaction. In the benzoin condensation, benzaldehyde is treated with cyanide ion to form an anion, which then attacks another benzaldehyde molecule to form, after the elimination of the original cyanide ion, a 2-hydroxyketone. 

Further steps in the synthesis of coumarin via the ortho-hydroxy benzaldehydes involve a Perkin reaction. Here, in the first instance, a cinnamic acid is obtained. The cinnamic acids are obtained more conveniently by the Wittig reaction of the aldehydes with the stable phosphoranes, Ph3P=C—COOEt. Indeed lithiation... 

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