Coumarins from phenols

An improvement in the synthesis of coumarins from phenols and P-keto esters results from the use of Zn to mediate a transesterification <02TL8583> and InCl3 is an efficient catalyst for the Pechmann reaction <02TL9195>. 

Synthesis of coumarins from phenols and p-oxo esters catalyzed by homogeneous acids, Lewis acids or clays (montmorillonite)... 

Reddy et al. (2009) documented a novel protocol for a Pechmann reaction involving the synthesis of substituted coumarins from phenols and P-ketoesters catalyzed by sulfuric acid supported on the silica gel surface (Scheme 5.28). The method has several distinct advantages such as a clean reaction profile, operational simplicity, use of nontoxic catalysts, and higher yields in short reaction time and provides a valuable addition to the existing methods for the synthesis of coumarins. 

Onzuka, K. Takigucbi, S. Fuse, K. Preparation of coumarins from phenols and alkoxymetbylenemalo-nic acid diesters. Jpn. Kokai Tokkyo Kobo JP 2004075643, 2004 Chem. Abstr. 2004,140, 217512. 

Until the late 1890s, coumarin was obtained commercially from only natural sources by extraction from tonka beans and deer tongue. Then synthetic methods of preparation and industrial manufacturing processes were discovered and developed starting principally from o-cresol, phenol, and sahcylaldehyde. Various methods can be used to obtain coumarin from each of these starting materials. 

From Phenol. In the type of condensation discovered by von Pechmaim in 1883, coumarin is formed by reaction of phenol [108-95-2] with malic (34), maleic, or fumaric acids (35—38) in the presence of concentrated sulfuric acid. 

A bismuth-catalyzed alkylation of warfarins has not been described, although a bismuth-mediated synthesis of the coumarin core structure 21 starting from phenols 19 and ethyl acetoacetate 20 is known (Scheme 17) [51]. The synthesis of coumarins proceeds in the same way as the above-described indene synthesis. The initial reaction of phenol 19 and ethyl acetoacetate 20 leads to the ester. 

Simonis chromone cyclization. Formation of chromones from phenol and (3-keto esters in the presence of phosphorus pentoxide, phosphorus oxychloride, or sulfuric acid. Coumarins may also be formed. 

Last, but not the least important is pure o-cresol, which is obtained as a co-product during p-cresol production based on sulfonation of toluene. Pure o-cresol is also produced from phenol through a methylation process. o-Cresol has been conveniently used for manufacture of Coumarin, a vital fine chemical, and also epoxy resins and ECN resins. o-Cresol is also being used as a building block of agrochemicals. 

Coumarins can be obtained directly, in a one-pot procedure, from phenols and a propiolate, using palladium or platinum catalysis. ... 

Coumarin synthesis from phenols and ethyl acetoacetate. ... 

Cyclizations. An intramolecular Sn2 process to form an oxaspirocycle as mediated by Amberlyst 15 is applicable to the synthesis of theaspirone. Under the influence of Dowex-50X2-200, coumarin derivatives are obtained from phenol and propynoic acid. ... 

Coumarins. A new synthesis of coumarins is directly from phenols and propynoic esters (8 examples, 46-79%). 

Ring synthesis of coumarins 9.3.2. / From phenols and 1,3-ketoesters... 

Coumarins can be obtained directly, in a one-pot procedure, from phenols and a propiolate using palladium(O) catalysis. The catalytic cycle is considered to involve a formyloxypalladium hydride reacting with the phenol to produce an aryloxypalla-dium hydride which adds to the alkyne. ... 

Gudej J (1991) Flavonoids, phenolic acids and coumarins from the roots of Althaea officinalis. Planta Med 57(3) 284-285 Gudej J, Tomczyk M (2004) Determination of flavonoids, tannins and ellagic acid in leaves from Rubus L. species. Arch Pharm Res 27(11) 1114-1119... 

The Simonis chromone synthesis is the reaction of a phenol la-c with a P-keto ester 2 using an appropriate acid promoter to generate a chromone or benzo-y-pyrone 3 (also called a benzo-l,4-pyrone). While compound 3 is actually a chromenone, for this article, whether the double bond is present or not, the system will be characterized as a chromone. The condensation is related to the Pechmann-Duisberg reaction, which yields coumarins from the condensation of a phenol with a P-keto ester and like its relative, the reaction conditions require the loss of water from the ketone moiety and alcohol from the ester moiety. 

Hoelderich, W. Laufer, M. C. Preparation of coumarin and derivatives from phenols and carboxyhc acids, P-ketocarboxylic acids, and derivatives in the presence of Nafion-silica composites, Deloxan, and/or narrow pore zeolites. PCT Int. Appl. WO 2004002980, 2004 Chem. Abstr. 2004,140, 77027. 

The use of these intermediates to produce shikimates is shown in Figure 6.32. In principle, anethole (53) and estragole (methyl chavicol) (52) are available from phenol, but in practice, the demand is met by extraction from turpentine. Carboxylation of phenol gives salicylic acid (38) and hence serves as a source for the various salicylate esters. Formylation of phenol by formaldehyde, in the presence of a suitable catalyst, has now replaced the Reimer-Tiemann reaction as a route to hydroxybenzaldehydes. The initial products are saligenin (189) and p-hydroxybenzyl alcohol (190), which can be oxidized to salicylaldehyde (191) and p-hydroxybenzaldehyde (192), respectively. Condensation of salicylaldehyde with acetic acid/acetic anhydride gives coumarin (50) and 0-alkylation ofp-hydroxybenzaldehyde gives anisaldehyde (44). As mentioned earlier, oxidation of phenol provides a route to catechol (184) and guaiacol (188). The latter is a precursor for vanillin, and catechol also provides a route to heliotropin (61) via methylenedioxybenzene (193). 

Back to our tenacity and purpose, he reported the synthesis of coumarins from the reaction of phenols with a carboxylic acid or ester containing a /1-carbonyl group (Scheme 1). 

Karimi et al. reported a variety of water-tolerant ordered nanoporous silicas functionalized with sulfonic acids for the Pechmann reaction, satisfying both recyclability and reactivity [65]. More recently, some of the authors developed a new family of periodic mesoporous silica chloride (PMSCl) synthesized by direct chlorination of SBA-15 with thionyl chloride the resulting material with 2D-hexagonal symmetry showed both high loading of Si-Cl moieties and thermal stability [66]. PMSCl efficiently catalyzed the synthesis of coumarins from a variety of phenols and ethyl acetoacetate, at 403 K, even much more than other sulfonic acids supporting mesoporous silicas, yielding coumarin 17 in almost quantitative yield in only Ih of reaction time. 

Coumarins are phenolic compounds widely distributed in the plant kingdom. The isolation of coumarin was first reported by Vogel in 1820 [1,2]. The name coumarin originates from a Caribbean word coumarou for the Tonka tree (Dipteryx odorata WUld, Leguminosae), which shares the characteristic smeU of these compounds and was known botanically at one time as Coumarouna odorata Aubl. 

As improvements over P-methylumbeUiferone (55—57), 4-methyl-7-amino-coumarin [26093-31-2] (12a) and 7-dimethylamino-4-methylcoumarin [87-014] (12b) (58—61) were proposed. These compounds are used for brightening wool and nylon either in soap powders or detergents, or as salts under acid dyeing conditions. They are obtained by the Pechmaim synthesis from appropriately substituted phenols and P-ketocarboxyflc acid esters or nitriles in the presence of Lewis acid catalysts (see Coumarin). 

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