Reactions Pechmann

The preparation of 4-methylcoumarin is an example of the Pechmann reaction, which consists in the interaction of a phenol with a 3-ketonic ester In the presence of a condensing agent (sulphuric acid, aluminium chloride, phosphorus oxychloride or pho.sphoric oxide) ... 

PEC-1000 Pechmann reaction Peclet numbers PE coatings Pectic acid Pectic acids [9046-40-6] Pectic materials Pectic substances Pectin... 

Pechmann reaction, 3, 802 Phenolsulfonephthaleins dyes, 6, 782 Phenosafranine applications, 3, 196 Phenothiazine, 3,7-dichloro-synthesis, 3, 1012 Phenothiazine, 5-ethyl-carbazoles from, 4, 152-153 Phenothiazine, 1-methyl-synthesis, 3, 1033 Phenothiazine, 10-phenyl-synthesis, 3, 1012 Phenothiazine, 10-sulfonyl-rearrangement, 3, 1012 Phenothiazines... 

For the synthesis of coumarins, the Pechmann reaction [145] is one of the most popular synthetic routes. As the reaction is conventionally carried out at high temperature, two microwave-assisted versions have been recently described. Besson and co-workers described the cyclocondensation of different m-amino phenols 226 with /1-ketoesters 227 on graphite/montmorillonite KIO support (Scheme 83). The use of graphite was crucial in the development of the reaction conditions. In fact, microwave irradiation of the reagents using different conditions gave poor results in terms of yields and purity. The optimized conditions, using a monomode microwave system, employed... 

John EVO, Israelstam SS (1961) Use of cation exchange resins in organic reactions. I. The von Pechmann reaction. J Org Chem 26 240-242... 

Biswas GK, Basu K, Barua AK, Bhattacharyya P (1992) Montmorillonite clay as condensing agent in Pechmann reaction for the synthesis of coumarin derivatives. Indian J Chem 31B 628-628... 

Sabou R, Hoelderich WF, Ramprasad D, Weinand R (2005) Synthesis of 7-Hydroxy-4-methylcoumarin via the Pechmann reaction with Amberlyst ion-exchange resins as catalysts. J Catal 232 34-37... 

Laufer MC, Hausmann H, Holderich WF (2003) Synthesis of 7-hydroxycoumarins by Pechmann reaction using Nation resin/silica nanocomposites as catalysts. J Catal 218 315-320... 

Efficient synthesis of 7-aminocoumarins has been performed via the Pechmann reaction between m-aminophenols and /i-ketonic esters. A comparative study of this procedure showed that use of microwave irradiation reduced the reaction time from several hours, if conventional heating was used, to a few minutes only (Eq. 22) [75]. 

Among polyheterocyclic systems, coumarins are synthesized by many routes, including the Pechmann reaction, which involves condensation of phenols with /fke-toesters [51]. This reaction, which has been the most widely applied method, has re-... 

Some 7-aminocoumarins-4-carboxylates [60 a] were synthesized by the Pechmann reaction, by microwave irradiation of the reactants on solid supports (graphite-K10) (Scheme 8.41). Synthesis of unsubstituted coumarins (C-4 position) has been also reported [60 b]. 

Passerini Reaction, 65, 1 Pauson-Khand reaction to prepare cyclopentenones, 40, 1 Payne rearrangement, 60, 1 Pechmann reaction, 7, 1 Peptides, synthesis of, 3, 5 12, 4 Peracids, epoxidation and hydroxylation with, 7, 7... 

While this reaction to form coumarin derivatives can be completed in mineral acids, research shows that the reaction was much faster in ILs even at room temperature. The same group used l-butyl-3-methylimidazolium hexafluoro-phosphate IL at high temperatures without employing any acid catalyst. The yields were comparable to chloroaluminate ILs with catalytic amounts of acid at room temperature. They also concluded that Bronsted acidity (produced by HF when [bmimJIPF ] contacts water) was not responsible for the observed activity. Singh et al have used l-butyl-3-methylimidazolium hydrogen sulfate IL in combination with microwave irradiation. They were able to synthesize coumarins in quantitative yields with drastic reduction in reaction times. Soares et al have used [bmim][NbCl6] IL to perform the Pechmann reaction using various phenols with ethyl acetoacetate to produce coumarin in moderate yields (-35%). 

Until the late 1890s, coumarin was obtained commercially only from natural sources by extraction from tonka beans. Synthetic methods of preparation and industrial manufacturing processes were developed starting principally from ortho-creso (Raschig process), phenol (Pechmann reaction) and salicylaldehyde (Perkin reaction). Various methods can be used to obtain coumarin from each of these starting materials. In order to be suitable for perfumery uses, synthetic coumarin must be highly pure (Bauer et al., 1988 Boisde Meuly, 1993). 

The formation of 2-oxopyran-5 -carboxylic acid (coumalic acid) from 2-hydroxybutanedioic acid (malic acid) is described in detail (63OSC(4)20l) and involves the decarbonylation and dehydration of the hydroxy acid. The formylacetic acid so formed then undergoes selfcondensation. This synthesis is an example of the Pechmann reaction usually associated with the synthesis of coumarins (benzopyran-2-ones). It will be observed that this route leads to pyran-2-ones which carry identical substituents at the 4- and 6-positions. 

One of the most reliable and widely used syntheses of coumarins involves the acid-catalyzed reaction between a phenol and a jS-keto ester, the Pechmann reaction (45CRV(36)1, 530R(7)l). An important aspect of the reaction is that it shows a dependency on all three reactants, which can be varied widely, thereby optimizing both the scope and conditions of the synthesis. As a consequence, satisfactory yields of coumarins substituted in either the benzene or pyranone ring or both rings can be obtained from readily accessible starting materials. 

Both fumaric and maleic acid give rise to coumarins on reaction with phenols. Initially, this route was considered different from the Pechmann reaction, but experimental evidence has been accumulated which suggests that it is simply a variant (73AJC899). Under the acidic conditions, the unsaturated acid could well produce some malic acid, which would then lose carbon monoxide and water as usual. Generally yields in the two approaches to coumarins are much the same. 

Although earlier investigations suggested that a Pechmann reaction on 3-substituted or 3,4-disubstituted phenols yielded only one product, it is now clear that this is not always the case (81T2021). The failure of earlier workers to isolate a second product is readily understood from the data in Table 6. As yet, it is not known whether this behaviour is a general feature of m-substituted phenols. The lack of formation of the 5- or 5,6-isomer in the reactions with ethyl acetoacetate may be a result of steric hindrance by the 4-methyl substituent. 

The Pechmann reaction is thought to proceed through electrophilic aromatic substitution of the phenol. The resulting /3-hydroxy ester then cyclizes and dehydrates to the coumarin, although of course dehydration may occur earlier in the sequence (Scheme 113). Indeed, the observation that 2-hydroxycinnamic acids readily yield coumarins in sulfuric acid (32JCS1681) renders these compounds or their esters plausible intermediates in the reaction. 

Table 6 Isomer Distribution in the Pechmann Reaction with 3-Substituted Phenols...

A /3-ketonitrile may usefully replace the 1,3-dicarbonyl compound in the Pechmann reaction. 2-Formyl-2-phenylacetonitrile and 1-naphthol react at 220 °C to afford the naphtho[l,2-6]pyran-2-one (366) (75JCS(P1)1869>. Under the more usual Pechmann conditions a number of products result, of which the acrylonitrile (367), the hydroxynitrile (368) and the dihydronaphthopyran-2-one (369) are significant, clarifying the disparate results of earlier workers. 

The vigorous conditions which are necessary serve to detract from the value of the Perkin synthesis, leading to the production of tarry material which adversely affects the yield of coumarin. Difficulties encountered in the synthesis of substituted o-hydroxybenzaldehydes also limit the application of this route. The obvious advantages of the method are that there are no doubts about the orientation of the product and that, unlike the Pechmann reaction, formation of the isomeric chromones is not possible. 

Aryl acetoacetates, which may be obtained by the reaction of phenols with diketene, are cyclized on treatment with sulfuric acid (54JCS854). The yields of coumarins are similar to those obtained by a Pechmann reaction on the phenol. 

There has been some controversy about the mechanisms of the Simonis and Pechmann reactions, which still remain in doubt. It has been suggested (50BSF1132) that the condensations proceed through a common oxonium ion (467). Dehydration to the phenoxyacrylic ester (468) is followed by cyclization to the chromone whilst a rearrangement to the substituted phenol (469) subsequently affords the coumarin (Scheme 171). 

Frere, S., Thiery, V. and Besson, T., Microwave accelaration of the Pechmann reaction on graphite/-montmorillonite K10 application to the preparation of 4-substituted 7-aminocoumarins, Tetrahedron Lett., 2001, 42, 2791-2794. 

Keywords phenol, /1-keto ester, Pechmann reaction, Knoevenagel reaction, cou-marin... 

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