Flavones, nitration

Flavone or 2-Phenylchromone, C15H10°2> and other flavones are the parents of a > number of yel natural dyes found in plants, leaves, fruits and flowers. The natural materials contain OH groups and occur un combined or as glucosides. Nitration occurs in 2-phenyl group giving a mixture of 2y- ... 

Nitration of hydroxypropiophenone (7-1) followed by conversion of the phenol to its methyl ether by means of methyl iodide provides the intermediate (7-2) the nitro group is then reduced to the corresponding amine (7-3) by catalytic reduction. The newly introduced amine is then replaced by a nitrile group by successive conversion to the diazonium salt by means of nitrous acid followed by treatment with cuprous cyanide (7-4). Reaction with aluminum chloride removes the methyl ether to afford the ortho acylphenol (7-5). This is converted to the chromone (7-6) as above by reaction with benzoyl chloride and sodium benzoate. The nitrile is next hydrolyzed to the carboxylic acid (7-7) by means of sulfuric acid. The acid is then converted to its acid chloride by means of thionyl chloride and that treated with 2-(A -piperidyl)ethanol (7-8). There is thus obtained flavoxate (7-9) [8], a muscle relaxant whose name reflects its flavone nucleus. 

Evidence has been presented that 2-hydroxychalcones are also transformed into flavones on reaction with thallium(III) nitrate (equation 16) (78TL3359). Such a method would be complementary to the isoflavone synthesis if it proves to be of general applicability. 

Flavylium salts are oxidized to flavones on treatment with thallium(III) nitrate in methanol. The reaction is considered to involve initial attack at C-2 by methanol. The resulting chromene (484) undergoes reaction with the thallium salt at C-3 and nucleophilic attack at C-4 by methanol to give an unstable adduct (485), which decomposes to the flavone... 

Favorskil rearrangement of 2-chloro-cyclohexanone, 39, 37 Ferric chloride, 36, 31 37, 77 Ferric nitrate hydrate, 39, 73 Ferrocene, 36, 31, 34 Ferrous chloride solution in tetrahy-drofuran, 36, 31, 34 Fischer indole synthesis, of 1,2-benzo-3,4-dihydrocarbazole, 30, 91 of 1,2,3,4-tetrahydrocarbazole, 30, 90 Flavone, 32, 72 Flavylium chloride, 32, 75 Flow meter, 34, 7 Fluorene, 34, 32 39, 44 Fluorene, 9-methyl-, 39, 43 9-Fluorenecarboxylic acid, 33, 37 o-Fluorobromobenzene, 39, 75... 

Ferric nitrate, 107 Ferrous sulfate, 237 Fischer esterification, 248 Flavones, 13, 14,424 Fluoranthene picrate, 391 Fluorene-9-carboxylic acid, 101 Fluorenol, 455, 506... 

Thomsen, L. L., Ching, L. M., Zhuang, L Gavin, J. B., and Baguley, B. C. (1991) Tumor-dependent increased plasma nitrate concentrations as an indication of the antitumor effect of flavone-8-acetic acid and analogues in mice. Cancer Res. 51, 77-81. 

Oxidative general breakdown of flavylium salts was utilised in early structural work on the natural compounds. Baeyer-Villiger oxidation is such a process, whereby the two halves of the molecule can be separately examined (after ester hydrolysis of the product). Flavylium salts can be oxidised to flavones using thallium(III) nitrate, and benzopyrylium itself can be converted into coumarin with manganese dioxide. ... 

C-Substitution of coumarins and chromones has been observed in both rings in strongly acidic media, in which presumably it is a hydroxy-benzopyrylium cation that is attacked, substimtion takes place at C-6, for example nitration. This can be contrasted with the dimethylaminomethylation of chromone, iodin-ation of flavones or the chloromethylation of coumarin where hetero-ring substitution takes place, presumably via the non-protonated (non-complexed) heterocycle (CAUTION CH2O/HCI also produces some CICH2OCH2CI, a carcinogen). 

The dehydrogenation of 2 -hydroxychalcones and flavanones to flavones, of l-(2-hydroxyaryl)alk-2-en-l-ones and chroman-4-ones to chromones and of thiochroman-4-ones to thiochromones can be accomplished using iodine in hot DMSO <97HCM223>. E-3-Styrylchromones result from the oxidative rearrangement of 5-aryl-l-(2-hydroxyphenyl)penta-2,4-dien-l-ones with thallium(lll) nitrate <97LA2065>. Dimethyldioxirane converts flavanones into flavones by way of the 2-hydroxyflavanone. This approach enables flavans to be converted to a variety of flavonoids <97TL4651>. 

The oxidation of a ( )-flavanone with Tl(ni) nitrate, Pb tetracetate, phenyliodonium diacetate (PIDA), or [hydroxyl(tosyloxy)iodo]benzene in trimethyl orthofonnate affords the corresponding ( )-2,3-dihydrobenzo[h]furan derivative as a major product. The structures, including the relative stereochemistry, and a plausible mechanism of formation are reported. The preferred formation of a flavone from the ( )-flavanone by PIDA is explained by quantum-chemical calculations on the intermediate formed by the addition of this reagent to the enol ether derivative of the ( )-flavanone." Formation of mixed anhydrides by rapid oxidation of aldehydes, activated by pivalic acid, Bu OCl in presence of pyridine and MeCN is catalysed by TEMPO (2,2,6,6-tetramethylpiperidin-l-oxyl). The anhydrides can be converted in situ to esters, secondary, tertiary or Weinreb amides in high yield. Oxidation of the aldehyde to 2-propyl esters is also possible using only catalytic amounts of pivalic acid." ... 

M. Meyer-Dayan, B. Bodo, C. Deschamps-Vallet, and D. Molko. The oxythallation of flavylium salts by thallic nitrate, a new synthesis of flavones. Tetrahedron Letters, 1978,3359. 

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