Halogenated chromones

Chromone, 3-hydroxymethyl-8-methoxy-antiallergic activity, 3, 707 Chromone, 7-methoxy-chlorosulfonation, 3, 708 Chromone, 7-methoxy-2-methyl-chloromethylation, 3, 708 Chromone, 2-methyl-chloromethylation, 3, 697 halogenation, 3, 709 IR spectra, 3, 596 mass spectra, 3, 613 oxidation, 3, 709 reactions... 

Whereas benzopyrylium salts are resistant to electrophilic substitution, even in the benzene moiety, the benzopyrones [coumarins (81), isocoumar-ins (82), and chromones (83)] are readily halogenated in either ring, with... 

Chloroquinolines are reactive groupings due to electron-deficient carbon to which the halogen is attached. This carbon is electron-deficient due to the combined electron-withdrawing effects of the chlorine substituent and the quinoline nitrogen. The electrophilic carbon is thus able to react readily with nucleophiles present in the body. The impact of this grouping on a molecule is illustrated by 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate (Figure 8.28). In contrast to many related compounds (chromone-carboxylates) lacking the chloroquinoline, 6-chloro-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate is excreted as a... 

Replacement of halogens attached to a pyran-4-one ring has only recently been studied. The lability of a 2-chloro atom in the chromone ring has been known since 1960. It is readily displaced by nucleophiles and reductively displaced by hydrogen (Scheme 32) <60CR(250)2819, 75AP385, 77H(6)1581>. 

A chlorocarbonyl group ortho to a fluorine atom activates the halogen towards nucleophilic displacement. In the synthesis of a number of polyfluorinated chromones the 1,3-diketo side-chain is introduced using ethyl acetoacetate in the presence of magnesium ethoxide. Cyclization occurs on addition of sulfuric acid (70JOC930). 

Syntheses and reactions of halogen-containing chromones 03UK550. 

This strategy yielded a small collection ofindoloquinolizines with yields ranging from 20 to 91%. Low yields were observed in the case of halogen-substituted chromones, and the low-yielding step was found to be the phosphine-catalyzed [4-1-2] annulation of 3-formylchromones 36 with acetylene dicarboxylates 37. Therefore, an alternative domino reaction was developed to bypass this phosphine-catalyzed reaction in order to increase the yield of these halogenated indoloquinolizines. 

The transformation is selective for the formation of C-2 substituted chromones and is tolerant toward a number of functional groups including nitro, free hydroxyl, acetyl, triflates, trifluoromethyl, and halogens (Scheme 24.41). The Backvall group subsequently reported a similar transformation that enabled the Pd-catalyzed coupling of arenes with cyclic saturated ketones [37]. 

Chromone-2-carboxylic acids carrying alkyl or halogen substituents on the benzene ring have been synthesised by this method but the yields obtained are not quoted [101-104], except in a patent [50] which describes the synthesis of the bischromone (24) from diethyl acetylenedicarboxylate and l,5-bis(4-hydroxyphenoxy)pentane in 15-5 per cent yield. 

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