Chromone bromination

Chromone, 7-hydroxy-2-methyl-bromination, 3, 707 Chromone, 3-hydroxymethylene-synthesis, 3, 821... 

Chromone-3-carbonitrile oxide obtained from 3-formylchromone oxime by bromination and subsequent dehydrobromination underwent cycloaddition reactions with terminal alkenes to give isoxazolines 34 (175). 

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. 

While treatment in HBr + AcOH by the Tarbell method424 leads directly from allylphenols 168 to compounds 169, other methods involve the formation of the brominated derivative obtained by adding HBr (in the presence of diphenylamine) to the allylphenol.432 Ring closure is effected by sodium ethoxide. Thus, the ll//-furo[3,2-a]xanthone derivative (177) can be obtained either directly from the allyl derivative (175) or via the bromo derivative (176).432 433 Similarly, 179 has been obtained from the chromone 178.434... 

Bond angles and lengths for 3-bromoflavone have been determined <82AX(B)983>. Whilst the two rings of the chromone system are essentially coplanar, the 2-phenyl group is twisted by 45.9° relative to the rest of the molecule apparently the steric interaction between the bromine atom at C-3 and H-2 outweighs the resonance stabilization which would be associated with a completely planar structure. 

A 2-methyl group of pyran-4-ones, e.g. (471), and chromones is susceptible to halogena-tion with either bromine or NBS and advantage has been taken of this in the synthesis of 3-methylchromone-2-carboxaldehyde (474) from 2,3-dimethylchromone (472) through the dibromide (473) (80JCR(S)159). 

A bromine atom on the benzene ring of chromones takes part in the Rosenmund-von Braun reaction to give moderately good yields of the nitrile, for example ethyl 8-cyano-6-methylchromone-2-carboxylate (545) (72JCS(Pl)779). Iodochromones and iodoflavones undergo the Ullmann reaction to form bis-compounds, some of which occur naturally or are related to such biflavonoids (B-75MI22302, 72JMC583). 

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... 

Addition of other molecules to the double bond is not common, but 2,3-dihalogeno-chroman-4-ones have been prepared from chromones using sulfuryl chloride (67CHE624) or bromine in carbon disulfide (25CB1612). Reaction with NBS in aqueous DMSO affords 3-bromo-2-hydroxychroman-4-one (75JHC981). 

The production of a 2-unsubstituted chromone by this route requires the use of triethyl orthoformate. Reaction with dimethylformamide dimethyl acetal, followed by an electrophile, bromine in the example, gives 3-substituted chromones. ... 

At a lower oxidation level, orffto-hydroxy-acyl-arenes undergo base-catalysed aldol condensations with aromatic aldehydes to give chalcones, °° which can be cyclised to 2,3-dihydro-chromones via an intramolecular Michael process the dihydro-chromones can in turn be dehydrogenated to produce chromones by a variety of methods, for example by bromination then dehydrobromination or by oxidation with the trityl cation, iodine, dimethyldioxirane or iodobenzene diacetate. ° ... 

The concept utilised was based on a retrosynthetic analysis comprising a nicotinic acid derivative (41) and a dihydroxychromone. The nicotinic acid moiety was prepared by lithiation of nicotinaldehyde followed by treatment with trimethyltin chloride. After benzoylation of the chromone noreugenin to protect the free phenolic group the compound was brominated to yield (42) and the two compounds formed were reacted with the nicotinic derivative to give a C-C bond with either the 6 or 8 of the chromone to give a compound such as (43) from which isoschumanniophytine or schumanniophytine respectively could be easily obtained by debenzoylation and lactonisation. 

An ester of l-thiochromanone-2-carboxylic acid, prepared from thiophenol and chlorosuccinic acid, may be brominated and the product dehydrobrominated by heating with pyridine to give an ester of 1-thio-chromone-2-carboxylic acid [63], The overall yield from thiophenol is about 12 per cent. 

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