Phenols coumarins

Complex phenolics Coumarins, phenolic quinones, lignins, flavonoids, stilbenes, hydrolyzable tannins, condensed (or catechin) tannins, phenolic lipids... 

Rhododendron mucronatum G. Don Bai Du Juan Hua (white azalea) (flower) Essential oil, germacrone, farreol, grayanotoxin, gossypetin, azaleatin, 5-methyl kaempferol, 5-methyl myricetin, syringic acid, dihydroquercetin, coumarins, phenolic acid, p-hydroxybenzoic acid, protocatechuic acid, vanillic acid.48 Treat cough, asthma, headache, respiratory infection. 

N.A. Iridoid glycosides, flavonol glycosides, coumarins, phenolic acids, sterols, triterpenoids, tannins." Stimulate digestive secretions, treat fluid retention, scabies, and fever. 

This reagent intensifies and stabilizes the existing fluorescence of the coumarins. Phenol carboxylic acids fluoresce blue or blue-green (e.g. chlorogenic or caffeic acid)... 

Terpenes, coumarins, phenol carboxylic acid.s, valepotriates... 

Copigmentation involves complexation phenomena, generally at low energy (hydrogen bonds and hydrophobic interactions), either between the various forms of anthocyanins or between antho-cyanins and other, mostly colorless, phenolic compounds (coumarins, phenolic acids, flavonols, fla-vanols, etc.) These bulky complexes modify the cation resonance and prevent the substitution of carbons 2 and 4 (Mazza and Brouillard, 1987). 

Phenolic compounds are a diverse group of phytochemicals classified into flavOTioids, phenolic acids, lignans, coumarins, phenols, phenylpropanoids, quinines, stUbenoids, and xanthmies. Flavraioids, which make up the largest cadre among phenolics, are further subdivided into anthocyanins, ilavanols including proanthocyanidins, flavo-nols, dihydrollavonols, flavones, isoflavonoids, flavonones, chalcones, and... 

For the preparation of 4-substituted coumarins, a phenol may be condensed with ethyl acetoacetate under the influence of sulphuric acid. Thus resorcinol (II) readily undergoes this condensation (which is represented diagrammatically above) to give 7-hydroxy-4-methyl-coumarin (III). Note that the coumarins, like all 2 pyrones, are systematically lactones. 

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). 

Make acid yields coumaUc acid when treated with fuming sulfuric acid (19). Similar treatment of malic acid in the presence of phenol and substituted phenols is a facile method of synthesi2ing coumarins that are substituted in the aromatic nucleus (20,21) (see Coumarin). Similar reactions take place with thiophenol and substituted thiophenols, yielding, among other compounds, a red dye (22) (see Dyes and dye intermediates). Oxidation of an aqueous solution of malic acid with hydrogen peroxide (qv) cataly2ed by ferrous ions yields oxalacetic acid (23). If this oxidation is performed in the presence of chromium, ferric, or titanium ions, or mixtures of these, the product is tartaric acid (24). Chlorals react with malic acid in the presence of sulfuric acid or other acidic catalysts to produce 4-ketodioxolones (25,26). 

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. 

The Pechmaim reaction has found extensive appHcations for the synthesis of numerous coumarin derivatives (39). Coumarin derivatives substituted in the pyrone ring can be obtained by condensing phenol with beta-ketoesters. For example, 4-methylcoumarin (3) is obtained with ethyl acetoacetate... 

Coumarin can also be formed by the reaction of phenol with diketene (40). Similarly, diphenols can react with hydroxycarboxyUc acids or beta-ketoesters to give hydroxycoumaria derivatives. The reaction of resorciaol with malic acid produces umbeUiferone (7-hydroxycoumaria) and its reaction with ethyl acetoacetate gives beta-methylumbeUiferone (7-hydroxy-4-methylcoumaria). 

Coumarin synthesis trom phenols and ethyl acetoaceiaie. 

Comforth has reviewed literature reports and independently studied the special cases of reaction of 1 with salicylaldehyde and with 2-acetoxybenzaldehyde. Coumarins (10) are afforded in the condensation of 1 with salicylaldehyde or its imine, whereas when 2-acetoxybenzaldehyde is used, acetoxy oxazolone 12 is the major product. The initial aldol condensation product between the oxazolone and 2-acetoxybenzaldehyde is the 4-(a-hydroxybenzyl)oxazolone 11, in which base-catalyzed intramolecular transacetylation is envisioned. The product 9 (R = Ac) can either be acetylated on the phenolic hydroxy group, before or after loss of acetic acid, to yield the oxazolone 12, or it can rearrange, by a second intramolecular process catalyzed by base and acid, to the hydrocoumarin, which loses acetic acid to yield 10. When salicylaldehyde is the starting material, aldol intermediate 9 (R = H) can rearrange directly to a hydrocoumarin. Comforth also accessed pure 4-(2 -hydroxyphenylmethylene)-2-phenyloxazol-5(4//)-one (13) through hydrolysis of 12 with 88% sulfuric acid. 

The distributions of phenolic isomers in hydroxylations in the animal body arc often similar to those obtained by Fenton s reagent. For example, the hydroxylation of coumarin by the rabbit gives the six hydroxycoumarins in amounts decreasing in the order 3- >7->6- >8- >4- /—5-, whereas Fenton s reagent gives mainly the 3-, 5-, and 7-derivatives with traces of the 6- and 8-derivatives. It may, however, be misleading to draw conclusions about the nature of... 

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... 

A modified Pechmann microwave-assisted reaction has been reported using an electron-rich phenol 229 and an a,/l-unsaturated acid in order to obtain coumarins without a substituent in position 4 [147]. Even in this case, the use of an acid solid catalyst (the support) was needed. Best results were obtained with Dowex or Amberhte-15 at 120 °C for 15 min (Scheme 84). 

Alkynoates react with electron rich phenols to give coumarins with good regioselectivity in the presence of formic acid and a Pd-catalyst Yields are good even in instances where the Pechmann synthesis is reported to be unreliable <96JA6305>. 

Tenerife and La Palma, revealed the existence of luteolin and an array of simple phenolic derivatives as well as three known phytosterols, B-amyrin, sitosterol, and stigmasterol. The phenols identified comprised a set of phenylpropanoids myristicin [566] (see Fig. 6.16 for structures 566-573), methyleugenol [567], todadiol [568], todatriol [569], crocatone [570], elemicin [571], apiole [572], and the coumarin scopoletin [573]. The occurrence of these compounds is recorded in Table 6.5. The differences between the two profiles were taken by Gonzalez and his co-workers... 

Arcmatic compounds phenols, phenolic acids, cinnamic acid derivatives, coumarins, flavonoids, quinones, and tannins, all of which are aromatic compounds, comprise the largest group of secondary plant products. They are often referred to as "phenolics" and have been identified as allelopathic agents in more instances than all of the other classes of compounds combined 5). 

The 12-membered macrocyclic triamine bearing a phenol pendent (591) was synthesized by one-pot annealation from coumarin and l,7-diamino-4-azaheptane. Upon coordination to Ni, the pendent phenol readily dissociates its proton at acidic pH and becomes a strong fourth donor.1506... 

Methylcoumarin is prepared by the condensation of phenol and acetoacetic ester. Concentrated sulfuric acid1,2 and 73% sulfuric acid have been used.3 4 The method given here was mentioned by Sethna, Shah, and Shah,6 and the procedure is adapted from that of the same authors 6 for another coumarin derivative. 

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-... 

Plant metabolism can be separated into primary pathways that are found in all cells and deal with manipulating a uniform group of basic compounds, and secondary pathways that occur in specialized cells and produce a wide variety of unique compounds. The primary pathways deal with the metabolism of carbohydrates, lipids, proteins, and nucleic acids and act through the many-step reactions of glycolysis, the tricarboxylic acid cycle, the pentose phosphate shunt, and lipid, protein, and nucleic acid biosynthesis. In contrast, the secondary metabolites (e.g., terpenes, alkaloids, phenylpropanoids, lignin, flavonoids, coumarins, and related compounds) are produced by the shikimic, malonic, and mevalonic acid pathways, and the methylerythritol phosphate pathway (Fig. 3.1). This chapter concentrates on the synthesis and metabolism of phenolic compounds and on how the activities of these pathways and the compounds produced affect product quality. 

Simple phenolic compounds include (1) the phenylpropanoids, trans-cinnamic acid, p-coumaric acid and their derivatives (2) the phenylpropanoid lactones called coumarins (Fig. 3.4) and (3) benzoic acid derivatives in which two carbons have been cleaved from the three carbon side chain (Fig. 3.2). More complex molecules are elaborated by additions to these basic carbon skeletons. For example, the addition of quinic acid to caffeic acid produces chlorogenic acid, which accumulates in cut lettuce and contributes to tissue browning (Fig. 3.5). 

Coumarins are formed by the intramolecular hydroarylation of an activated alkyne. The basic starting materials for this fast, efficient and general Pd-catalysed reaction are phenols and alkynoic acids (Scheme 42), An intermolecular version in which electron-rich phenols react with 4-methoxycinnamic acid leads to high yields of 3,4-dihydrocoumarins... 

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