Pechmann approach

The classical Pechmann approach for the synthesis of coumarins via the micro-wave-promoted reaction [68] has been extended to solvent-free system wherein salicy-... 

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. 

The Pechmann synthesis is unsuitable for acid-sensitive phenols, as for example the furo[2,3 -6]benzofuran derivative (373). An alternative approach uses the enhanced electrophilic character of a vinyl bromide in the presence of zinc carbonate to construct a suitable side-chain adjacent to the phenolic group (71JA746). In the examples cited, ring closure occurred under the mild conditions to form the pyranone ring of the aflatoxins (374). Since neither sodium nor potassium carbonate proved effective, it was considered that chelation of the zinc facilitated the carbon-carbon bond formation (Scheme 115). 

Coumarins are readily accessed via the Pechmann condensation of phenols and 1,3-dicarbonyl compounds, which proceeds via electrophilic aromatic substitution of the phenol followed by dehydration and lactonization <1984CHEC, 1996CHEC-II>. In this manner, the amino acid bearing coumarins 676 are formed by a Pechmann condensation of phenols and 2-amino-6-ethoxy-4,6-dioxohexanoic acid 677 (Scheme 161) <2004AGE3432>. The popularity of this approach results from the wide range of readily available substrates (phenols and 1,3-dicarbonyl compounds). However, a major drawback is that electron withdrawing groups on the phenolic component dramatically reduces the yield of a Pechmann reaction. 

Given the somewhat diminished reactivity between some 1,3-dipoles and dipolarophiles, several different approaches have been examined to expedite the Pechmann pyrazole synthesis. The general idea behind the two approaches discussed below is very similar both rely on manipulating the HOMO and LUMO of the reacting partners.The first approach relies on the ability of Lewis acids to lower the energy of the dipolarophile s LUMO,... 

In an alternative approach toward reducing the acidic waste stream generated from the Pechmann condensation, a range of heterogeneous catalysts have been investigated (see Table 1). Resin sulfonic acids, acidic zeolites, acidic clays,and acid-treated metal oxides "" have all... 

The Pechmann condensation provides a unified synthetic approach toward the preparation of many poly-substituted coumarins. Electron-rich phenols e.g., resorcinol, pyrogallol, phloroglucinol) are readily converted to the corresponding coumarins. Less electron-rich phenols (including phenol itself) provide reduced yields of coumarin products, and monohydric phenols... 

Retrosynthetic analysis of the target coumarin skeleton provides two major synthetic routes (Figure 10.1). Route A requires an aromatic o-hydroxy carbonyl compound and a two-carbon fragment observed in Knoevenagel and Perkin reactions reflecting the [4h-2] approach for the construction of six-membered heterocycles. Route B represents the reaction between phenols and three carbon fragments associated with the Pechmann cyclization. In recent years, newer synthetic methodologies have also been applied to the synthesis of a variety of coumarins that have avoided the use of concentrated sulfuric acid. The present chapter reviews various... 

In this approach, good yields are reported, even in cases in which the von Pechmann synthesis gives unsatisfactory results. 

Wu J, Diao T, Sun W, LiY (2006) Expeditious approach to coumarins via Pechmann reaction catalyzed by molecular iodine or AgOTf. Synth Commun 36 2949-2956... 

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