Aliphatic Perkin reaction

The condensation of aromatic aldehydes with anhydrides is called the Perkin reaction When the anhydride has two a hydrogens (as shown), dehydration always occurs the P-hydroxy acid salt is never isolated. In some cases, anhydrides of the form (R2CHC0)20 have been used, and then the hydroxy compound is the product since dehydration cannot take place. The base in the Perkin reaction is nearly always the salt of the acid corresponding to the anhydride. Although the Na and K salts have been most frequently used, higher yields and shorter reaction times have been reported for the Cs salt. Besides aromatic aldehydes, their vinylogs ArCH=CHCHO also give the reaction. Otherwise, the reaction is not suitable for aliphatic aldehydes. ... 

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 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). 

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-... 

Perkin reaction Condensation of aromatic aldehydes with the anhydrides of aliphatic carboxylic acids to afford a,P-unsaturated carboxylic acids. 338... 

The Perkin reaction is capable of numerous modifications, since in place of benzaldehyde, its homologues, its nitro- and oxy-derivatives, etc., may be used. On the other hand, the homologues of sodium acetate may be used as has been pointed out. The condensation in these cases always takes place at the carbon atom adjoining the carboxyl group. Halogen substituted aliphatic adds will also react thus from benzaldehyde and chloracetic add, chlordnnamic acid is obtained ... 

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-... 

Simple aliphatic aldehydes and ketones cannot be used as the carbonyl component in the Perkin reaction. Knoevenagel5 reported the successful condensation of aldehydes and ketones with malonic acid in the presence of ammonia or amines. The most satisfactory method uses pyridine as a catalyst and is known as the Doebner modification.6 Thus, acetaldehyde 18 reacts with malonic acid (19) in the presence of a pyridine catalyst to afford the acid 20 in 60% yield. 

The methylene group of malonic or cyanoacetic acid is sufficiently reactive to condense under mild conditions with aliphatic or aromatic aldehydes or with ketones. Initially such reactions were carried out in the same way as the Perkin reaction, in acetic acid solution or in the presence of acetic anhydride however, use of acetic anhydride is unnecessary. 

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. ... 

Aliphatic aldehydes give low or no yields of acid. Coumarin can be prepared by a Perkin reaction of salicylaldehyde and acetic anhydride in the presence of triethylamine (eq 33). 

Aliphatic aldehydes are easily converted to the enol acetate using acetic anhydride and potassium acetate (eq 52). This reaction only works for aldehydes and is the principal reason for the failure of aldehydes to succeed in the Perkin reaction. Triethy-lamine and DMAP may also catalyze the reaction. 

In the previously discussed Perkin reaction, limiting the choice of aldehyde to one containing no a-H atoms, i.e., benzaldehyde, is more important because of the less-labile H-atoms present in the aliphatic anhydrides. 

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

Cinnamic Acid.—The reaction, which takes place when an aldehyde (aliphatic or aromatic) acts on the sodium salt of an aliphatic acid in presence of the anhychide, is known as Perkin s reaction, and has a ery wide application. Accoid-ing to the result of Fittig s researches on the properties of the unsaturated acids described below, the reaction occurs in two steps. The aldeh) de forms first an additive compound with the acid, the aldehyde caibon attaching itself to the n-carbon ii.e.i nevt the carbovyl) of the acid. A saturated hydiOKy-acid is formed, which is stable, if the a-carbon is attached to only one atom of hydrogen, as in the case of isobutync acid,... 

Packer, J.E., Willson, R.L., Hahnemann, D. and Asmus, K.-D. (1980). Electron transfer reactions of halogenated aliphatic peroxyl radicals measurements of absolute rate constants by pulse radiolysis. J. Chem. Soc. Perkins Transact. II, 296-299. 

The methylene groups of hippuric acid and malonic acid are much more reactive than that of acetic acid. They may be caused, therefore, to condense with aldehydes under much milder conditions, e.g. by the action of pyridine. The use of malonic acid forms an extension of Perkin s reaction to the aliphatic series (Doebner), e.g. 

Zappey, H.W. Ingemann, S. Nibbering, N.M.M. Isomerization and Fragmentation of Aliphatic Thioether Radical Cations in the Gas Phase Ion-Neutral Complexes in the Reactions of Metastable Ethyl Propyl Thioether Ions. J. Chem. Soc., Perkin Trans. 2 1991, 1887-1892. 

Al-Sheikhly Ml, Schuchmann H-P, von Sonntag C (1985) y-Radiolysis of N20-saturated formate solutions. A chain reaction. Int J Radiat Biol 47 457-462 An bar M, Meyerstein D (1964) Isotope effects in the hydrogen abstraction from aliphatic compounds by radiolytically produced hydrogen atoms in aqueous solutions. J Phys Chem 68 3184-3167 Anbar M, Meyerstein D, Neta P (1966) Reactivity of aliphatic compounds towards hydroxyl radicals. J Chem Soc Perkin Trans 2 742-747... 

Hug GL, Bonifacic M, Asmus K-D, Armstrong DA (2000a) Fast decarboxylation of aliphatic amino adds induced by 4-carboxybenzophenone triplets in aqueous solutions. A nanosecond laser flash photolysis study. J Phys Chem B 104 6674-6682 Hug GL, Carmichael I, Fessenden RW (2000b) Direct EPR observation of the aminomethyl radical during the radiolysis of glycine. J Chem Soc Perkin Trans 2 907-908 Hunter EPL, DesrosiersMF, Simic MG (1989) The effect of oxygen, antioxidants and superoxide radical on tyrosine phenoxyl radical dimerization. Free Rad Biol Med 6 581-585 Ito O (1992) Flash photolysis study for reversible addition reactions of thiyl radicals with olefins and acetylenes. Trends Phys Chem 3 245-266... 

Part 7. Reactions of aliphatic a-substituted nitro compounds. /. Chem. Soc. Perkin Trans. 2 2001, 1557-1565. 

Node M, Hon H, Fujita E (1976) Demethylation of aliphatic methyl ethers with a thiol and boron trifluonde J Chem Soc Perkin Trans I 2237-2240 Sarkanen KV, Ludwig CH (1971) Definition and nomenclature In Sarkanen KV, Ludwig CH (eds) Lignins Occurrence, formation, structure and reactions Wiley-Interscience, New York, 1-17... 

Semmes, D.H., Ravishankara, A.R., Gump-Perkins, C.A., Wine, P.H. (1985) Kinetics of the reactions of hydroxyl radical with aliphatic aldehydes. Int l. J. Chem. Kinetics 17, 303-313. 

Simple aliphatic or aromatic ketones are not suitable substrates in the Pericin transformation. Similarly, aliphatic aldehydes are not generally acceptable components in this reaction. This long-known limitation was studied by Crawford and Little. They demonstrated that many aliphatic aldehydes give diacetates and enol acetates when heated with acetic anhydride, with or without sodium acetate, suggesting this side reaction causes the typical Perkin process to fail. Semmeler had previously obtained similar results. They did show, however, that several short chain aldehydes, as well as frowj-citral (16), undergo the Perkin condensation with p-nitrophenylacetic anhydride the p-nitrophenyl substituent activates the anhy-... 

In 1868 W. H. Perkin, Sen., discovered that heating the sodium derivative of salicylaldehyde with acetic anhydride led to coumarin,882 and this reaction has gained great importance as a method of synthesizing <%,/ -unsaturated acids. The method consists of heating an aromatic aldehyde with the anhydride of an aliphatic acid and the sodium or potassium salt of the same acid. This reaction, the Perkin synthesis, can also be carried out with cinnamaldehyde but not with purely aliphatic aldehydes. 

A Perkin-type reaction gives a different result when an aromatic — or an aliphatic — aldehyde reacts with succinic acid in the molar ratio 1 1 the products then are y-aryl- or y-alkyl-paraconic acids and, when heated, these lose carbon dioxide and give the / ,y-unsaturated acids together with small amounts of the corresponding butyrolactone ... 

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