Flavylium salts

The reaction of flavylium salts (403a) with hydroxylamine in pyridine gave 2,5-dihy-droisoxazoles (404) in an analogous manner (75T2884). Pyrimidines have also been converted into isoxazoles, and the reaction of the pyrimidines (405) with hydroxylamine hydrochloride gave the isoxazoles (338). 

Jurd reported the isolation of a 2//-3-isoxazoline by the reaction of the flavylium salt (488) with hydroxylamine. Gentle heating of the material caused isomerization to the more stable 2-isoxazoline. Treatment with base generated an a,/3-unsaturated oxime which on photolysis regenerated the starting flavylium salt (Scheme 129) (70CI(L)624). 

Garcia-Viguera, C. and Bridle, R, Influence of structure on colour stability of anthocyanins and flavylium salts with ascorbic acid, Food Chem., 64, 21, 1999. 

Jurd, L., Anthocyanidins and related compounds. XL Catechin-flavylium salt condensation reactions. Tetrahedron, 23, 1057, 1967. 

Pina, R, Caffeine interaction with synthetic flavylium salts. A flash photolysis study for the adduct involving 4,7-dihydroxyflavylium, J. Photochem. Photobiol. A Chem., 117, 51, 1998. 

Timberlake, C.F. and Bridle, P., Flavylium salts anthocyanidins and anthocyanins. Structural transformations in acid solutions, J. Sci. Food Agric., 18, 473, 1967. 

There are numerous examples of benzopyrylium salts, benzopyransand benzopyranones, and frequently they have trivial names that reflect their long history (see Box 5.1). Many are natural products, and frequently these compounds contain hydroxy or alkoxy groups (sometimes in the form of a sugar residue). Polyhydroxylated natural products based upon 2-phenylbenzopyrylium (flavylium) salts and with ether linkages to sugars are called anthocyanins, whereas without their sugars they are known as anthocyanidins. 

Absorption spectra have also been used in the reexamination of pH-dependent color and structural transformations in aqueous solutions of some nonacylated anthocyanins and synthetic flavylium salts." ° In a recent study, the UV-Vis spectra of flower extracts of Hibiscus rosasinensis have been measured between 240 and 748 nm at pH values ranging from 1.1 to 13.0." Deconvolution of these spectra using the parallel factor analysis (PARAFAC) model permitted the study of anthocyanin systems without isolation and purification of the individual species (Figure 2.21). The model allowed identification of seven anthocyanin equilibrium forms, namely the flavylium cation, carbinol, quinoidal base, and E- and Z-chalcone and their ionized forms, as well as their relative concentrations as a function of pH. The spectral profiles recovered were in agreement with previous models of equilibrium forms reported in literature, based on studies of pure pigments. 

The molecular structures of various synthesized flavonoid derivatives have been examined by x-ray crystallography in recent years,including a 3-methyl-substituted flavylium salt with photochromic properties and some phosphorylated flavones. ... 

Pina, F. Thermodynamics and kinetics of flavylium salts — Malvin revisited, J. Chem. Soc., Faraday Trans., 94, 2109-2116, 1998. 

Jurd, L. and Waiss, A.C.Jr, Anthocyanins and related compounds — VI. Flavylium salt-phlor-oglucinol condensation product. Tetrahedron 21, 1471, 1965. 

Mazza, G. and Brouillard, R., Color stability and structural transformations of cyanidin 3,5-diglucoside and four deoxyanthocyanins in aqueous solutions. J. Agric. Food Chem. 35, 1987. Roehri-Stoeckel, C. et al.. Synthetic dyes simple and original ways to 4-substituted flavylium salts and their corresponding vitisin derivatives. Can. J. Chem. 79, 1173, 2001. 

Since the early contributions of Willstatter and Robinson, several alternative approaches following mainly two routes have been considered for synthesis of anthocyanins.One of the routes includes condensation reactions of 2-hydroxybenzaldehydes with acetophenones, while the other uses transformations of anthocyanidin-related compounds like flavonols, flavanones, and dihydroflavonols to yield flavylium salts. The urge for plausible sequences of biosynthetic significance has sometimes motivated this latter approach. In the period of this review, new synthetically approaches in the field have also predominantly been following the same general routes however, some new features have been shown in synthesis of pyranoanthocyanidins. 

In an interesting paper by Bernini et al., compounds with a flavonoid structure have been selectively oxyfunctionalized at the C-2 carbon atom by dimethyldioxirane (DMD). Products obtained in this way appeared to be useful starting materials to access anthocyani-dins. An example of this route is presented in Scheme 10.1. Here, 2,4-cw-flavane-4-acetate (A) was oxidized by DMD at room temperature, affording the corresponding C-2 hydroxy derivative (B) as the only product (63% yield). Further treatment of B with silica gel eliminated acetic acid to give C quantitatively. Then C was easily transformed into the flavylium salt (D) by simple addition of a 37% solution of HCl in water. 

New 3-desoxyanthocyanidins have been prepared according to a Grignard reaction of some flavones with appropriate alkyl- and aryl-magnesium bromides. The reaction of 5,7-dihydroxyflavone (chrysin) with an excess of phenylmagnesium bromide in THF under reflux conditions, followed by hydrochloric acid hydrolysis, afforded 1 in Scheme 10.2. Flavylium salts bearing a substituent at the 4-position are important compounds since they are known to be less sensitive to nucleophiles, especially water, and they give only minor amounts of the colorless pseudobases. ... 

Flavylium salts with 4-methyl substitution (e.g., 2 in Scheme 10.2) might be further gently reacted with aromatic aldehydes affording anthocyanidin pigments of the pyranoanthocyanidin type. ... 

Compared to the more common flavylium salts, these latter pigments showed large bathochro-mic shifts (from about 100 to 200 nm), thus providing blue-violet and green colors, which are difficult to obtain with anthocyanidins in general. 

Margarida, C.M. et al., Complexation of aluminium(III) by anthocyanins and synthetic flavylium salts. A source for blue and purple color, Inorg. Chim. Acta, 356, 51, 2003. 

Roehri-Stoeckel, C. et al.. Synthetic dyes simple and original ways to 4-substituted flavylium salts and their corresponding vitisin derivatives. Can. J. Chem., 79, 1173, 2001. 

The elimination of water (or acetic acid) also occurs during reductive acetylation of flavonols, leading to 3-acetoxyfiav-3-enes (27), which are converted into flavylium salts (28) in the acid medium. This reaction has been the subject of much study because of the complexity of the... 

Nucleophilic addition to benzopyrylium salts is another route to chromenes, but the attack may occur at the positions 2 or 4, thus giving rise to chrom-3-enes (30) or chrom-2-enes (31). Thus NaBH4 reduces simple flavylium salts to flav-2-ene121 (which, in its turn, behaves as a nucleophile and gives rise to dimeric products110) whereas 3-substituted... 

Arylbenzo[Z> ]furans are usually prepared from 3-substituted flavylium salts by oxidation. This route has been used to synthesize coumestones (e.g. coumestrol) (64JOC2602). 

Some attention has been paid to the NMR of flavylium salts (12) (65T3697) and to the glycosides of various flavonoids (65JOC4346,68JOC1571). 

Benzopyrylium salts are reduced by sodium borohydride to the 4/T-chromene but LAH yields the 2//-isomer. The reduction products of flavylium salts vary with the conditions used even the method of isolating the product has to be carefully controlled since, for example, 4/f-flavenes may be isomerized by contact with acid to 2//-flavenes. Flavylium... 

In view of these and similar reports, it is clear that the reduction products of pyrylium and flavylium salts depend to a considerable extent on the nature of any substituents present, the reducing agent and the precise conditions used. 

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... 

In this section the formation of benzopyrylium (632), isobenzopyrylium (633) and xanthy-lium (634) salts is covered in addition to the parent system. There is no separate treatment of flavylium salts, which are considered as phenyl derivatives of benzopyryliums. 

This route may be extended to the synthesis of flavylium salts through the reaction of an orthoformate with C-acyl derivatives of o-hydroxyacetophenone (72JOU2250). During this synthesis small amounts of 2,6-di-(2-hydroxyaryl)pyrylium salts are produced. If an excess of o-hydroxyketone is used in the reaction, the 2,6-diarylpyrylium salt becomes the major product (73JOU399). 

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