Chromone nitration

Electrophilic aromatic substitution of other benzo-fused v-deficient systems generally follows predictable pathways. Thus, benzopyrylium salts are in general resistant to electrophilic substitution even in the benzo-fused ring. Chromones behave somewhat similarly, although substitution can be effected under forcing conditions. Coumarins, on the other hand, undergo nitration readily in the 6-position while bromination results in substitution at the 3-position as a consequence of addition-elimination. 

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. 

The directing effect of a substituent in a chroman is sometimes different from that in chromone for example, bromination of the 7-methoxy compounds yields the 8-bromo-chromone not the 6-bromochroman, and nitration of 8-hydroxychromone gives mainly the... 

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... 

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>. 

Substituted 2-R -chromones are effective in the reaction with amidines to create R -containing pyrimidine derivatives. Reflux of chromones 13 with benzamidine hydrochloride or guanidinium nitrate in the presence of KOH yielded the pyrimidines 173 in moderate to high yields [87] (Scheme 55). 

When treated with chlorine in the light (CCI4, 60 C, 1 h), chromones 130 add a chlorine molecule at the double bond of the pyrone ring and, after elimination of HCl, they are converted into 3-chlorochromones 226a, which are readily nitrated to give 3-chloro-6-nitrochromones 226b [67,115] (Scheme 74). 

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