Chromones Benzopyran-4-ones

Chromones differ marginally in their chemistry from coumarins (ben-zopyran-2-ones) because the carbonyl group is now conjugated with the oxygen atom via the double bond of the heterocycle (see Box 5.2). This conjugation does not involve the benzene ring. 

As a result, chromones are rather more basic, and strong acids readily protonate the carbonyl oxygen atom, forming crystalline benzopy- 

Q Why should the Mamiich reaction with chromone take place at 

A The Mannich reaction proceeds through the intervention of the N,A dimethylmethyleniininium cation [Me N =CHJ, This is insufficiently electrophilic to react with the benzene ring under the mild reaction conditions. Similarly, were the electrophile to react with the carbonyl oxygen atom of the heterocycle, this reaction would be reversible, as an aminomethyl ether is relatively unstable in acidic media. Thus, it seems plausible that the chromone utilizes enol or enolate character to trap the electrophile at C-3, followed by deprotonation of the adduct to reform the chromone ring system ( heme 5.9). 

Under these conditions, the O-benzoyl derivative immediately enolizes and is O-acylated again to yield a dibenzoate. Without isolation, this product is cyclized by treatment with aqueous potassium hydroxide to yield 2-hydroxy-2,3-dihydroflavone. Dehydration to flavone is then effected by the action of glacial acetic acid containing sulfuric acid. 

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H-l-Benzopyran-4-ones — see Chromones 4H-l-Benzopyran-4-ones, 2-phenyl — see Flavones Benzopyranopyrazoles synthesis, S, 317, 341 Benzopyrano[4,3-c]pytazol-4-one synthesis, 3, 712 Benzopyrano[4,3-6]pyridine synthesis, 3, 712 Benzopyrano[4,3-ii]pyrimidine synthesis, 3, 712 Benzopyrans nomenclature, 1, 23 pyrylium salt synthesis from, 3, 873 reactions... 

Cyclisation of o-hydroxyphenyl ethynyl ketones under basic conditions is known to produce benzopyran-4-ones and benzofuranones by 6-endo-dig and 5-exo-dig processes, respectively. However, both cyclisations are reversible in aprotic media thereby generating anions, of which that derived from the pyranone is rapidly and irreversibly protonated and hence selective formation of the chromone results <96T9427>. 

In contrast to the benzoannelated nitrogen heterocycles, only a few kinds of benzoannelated systems without nitrogen have been described (Fig. 3.15). Five-mem-bered rings such as benzo[b]furans (336) [184, 461] and hydrobenzo[b]furans (337) (Scheme 3.41) [337, 462, 463] and six-membered rings like 4H-l-benzopyran-4-ones (4-chromones) (338) and 2H-l-benzopyran-2-ones (coumarines) (339) [96, 464, 465] 2,3-dihydro-4H-l-benzopyran-4-ones (chroman-4-ones) (340) [466] and 3,4-dihydro-lH-2-benzopyrans (isochromans) (341) [444] have been reported. 

This method is suited to the synthesis of natural benzofuran derivatives karanjin (111, R = R = H) (a furoflavone) and pongapin (111, RR = 0-CH2-0) have been prepared in this way,201 as well as khellin (26).315 From the chromone acetaldehyde (112), visnagin (113) (4-methoxy-7-methyl-5//-furo[3,2-g][l]benzopyran-5-one) was synthesized.310... 

Chromone (4 H-1 -benzopyran-4-one) (21) Xanthone (9H-xanthen-9-one) (22) Flavone (2-phenyl-4 W-1 -benzopyran-4-one)... 

Deprotonation of chromone 369 with lithium 2,2,6,6-tetramethylpiperidide followed by addition to aldehydes provided substrates which were converted directly to furo[3,4- ][l]benzopyran-9-ones (e.g., 371) upon acetal deprotection (Scheme 57) <2002S2341>. 

The reactivity of 47/-benzopyran-4-ones in Diels-Alder reactions is well documented <1987T3075>, and recently high asymmetric induction has been achieved in the reaction of 3-alkoxycarbonyl-substituted chromones with chiral auxiliaries and Danishefsky s diene <1991JOC2058>. It should be noted that 3-formylchromones can react as heterodienes in the stereoselective inverse electron Diels-Alder reaction with enol ethers <1994T11755> to provide a route to pyrano[4,3-A][l]benzopyrans a heterocyclic nucleus which occurs naturally in the fungal metabolite fulvic acid <1984CC1565>. The thermal Diels-Alder reaction of 477-pyran-4-one 405 in the presence of an excess of Danishefsky s diene 404 provided cycloadduct 406 (Equation 32) <1996H(43)745>. 

In the present study, we describe the effects produced by 3-formyl-chromones substituted at the 6-position. We evaluated their cytotoxicity against human tumor cell fines and normal cells, and also investigated the structurally related coumarine (2H- l-benzopyran-2-one) derivatives [24]. 

Chloroperoxidase catalysis by, 58, 302 in chlorination of pyrazoles, 57, 337 Chlorophyll, thioaldehyde synthetic intermediate to, 55, 3 Chlorosulfonyl isocyanate, reaction with 2-arylhydrazono-3-oxobutanoate, 59, 148 Chromatography, of [l,2,4]triazolo[l,5-a]-pyrimidines, 57, 106 Chrom-3-enes, see 2//-l-Benzopyrans Chromium tricarbonyl complexes of 3,5-diphenyl-l-(alkyl- or oxido-)-thiabenzenes, 59, 206, 227 indoles, lithiation of, 56, 181, 184 of pyridine, 58, 160 pyridines, lithiation of, 56, 230, 239 of 2f/-thiopyrans, 59, 227 Chromones, see l-Benzopyran-4-ones Cinnamonitrile, a-cyano-, condensations with thio-, seleno-amides, 59, 184, 186 Cinnoline, nitration, MO calculation, 59, 302... 

The chromones (4H-l-benzopyran-4-ones) have been reported to exhibit antifungal, antiviral, antimicrobial, antiallergic, antitublin, and antitumor activ-... 

The pyrano[3,2-c]xanthen-7-one exhibits the two absorption bands associated with a heteroatom at a peri position of the benzopyran nucleus. Pyrano[2,3-a]xanthen-12-one 44, in which the fusion of the chromone ring is reversed, shows an intense single band blue-shifted some 14 nm relative to 2,2-diphenyl-2//-naphtho[l,2-6]pyran [Xmax 403, 482 nm (PhMe)]. Both isomers are readily degraded <01HCA117>. It is noteworthy that 44 could not be... 

Similar results have been obtained for some reactions between phosphite triesters and the chlorides from heterocyclic carboxylic acids. The first of these to be reported were for the pyridinylcarbonyl chlorides. Here, 270 from 2-pyridinylcarbonyl chloride, and 271 from the 3- and 4-pyridinyl chlorides, were obtained presumably via the betaines Similarly, the acylphosphonate 274, from 273, reacted with more trialkyl phosphite (R = Me or Et), possibly via structures 275 and 276 (together with, in the latter case, the geometrically isomeric form) to give the isolated products, 277 and 278 (again as geometric isomers) With 4,4-dichloro-4//-benzopyran-2-ylcarbonyl chloride, a similar mechanism was postulated but with the loss of one chlorine atom (as in 279) to restore electron redistribution within the chromone system" the E structure was confirmed by X-ray crys-tallography ... 

Important derivatives of 4i/-chromene are chromone 5 (4//-l-benzopyran-4-one), flavon 6 (2-phenyl-4//-l-benzopyran-4-one) and xanthene 7 (note the exception to systematic numbering). They will be discussed in chapter 6.12. 

Suitably 3-substituted chromones take part in cycloaddition reactions. 3-Acyl derivatives react with 1-alkoxyalkenes in an eiu/o-selective fashion to form pyrano[4,3-/ ][l]benzopyran-10-one derivatives from which a range of chromones and chromanones can obtained (94T11755). 

The final target, 3-(IH-tetrazol-5-yl)chromones (5), were synthesized by the reaction of sodium azide in the presence of anhydrous aluminum chloride and 4-OXO-4H-1-benzopyran-3 -carbonitri les ( ) which were obtained in one step from with hydroxylamine (22, 2 ) (Figure 2). 

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