Chromone ring oxidative

Spirothiopyrans 45b including a benzopyrylium ring have been prepared in one step by condensation of 2-aminovinyl-3-formyl chromone-4-thione 47 with 1,2,3,3-tetramethylindolinium salts in ethanol (Scheme 25).90 The precursor 47 is prepared from 3-carboxymethylene-2-methyl-chromone-4-thione 48. First, oxidation of 48 with pyridinium dichromate in CH2C12, and then condensation with dimethyl formamide dimethyl acetal in benzene gave compound 47. 

The dibenzopyranone ring system may be viewed as a chromone with an additional fused benzene ring and thus generally related to the antiasthmatic mediator release inhibitor cromolyn (see Chapter 11). Two dibenzopyranones have in fact been investigated for this indication in the clinic. Friedel-Crafts cyclization of the substituted cresyloxybenzoic acid (2-1) in sulfuric acid leads to the dibenzopyranone (2-2). The methyl group is then oxidized to a carboxylic acid by means of chromic acid. The acid is then converted to its sodium salt, xanoxate sodium (2-3) [2]. 

Chromones are readily oxidized by permanganate or dichromate with opening of the pyran ring and the formation of a salicylic acid (402). Flavones and isoflavones are also degradatively oxidized for example oxidation of munetone (403) with alkaline hydrogen peroxide yields 2-methoxybenzoic acid and 4-hydroxy-2-isopropylbenzofuran-5-carboxylic (isotubaic) acid. 

Other ring transformations giving isoxazoles (or isoxazolines capable of conversion into isoxazoles) are as follows ring expansion of oxirans41 and oxetanones42 ring contraction of pyrimidines, pyrimidinium salts, pyrimidine JV-oxides,43 pyrylium salts,44 ketonylidenepyrans,45 chromones, thiochromones, chromylium salts,46-51 and oxazinones 52 photoisomeriza-... 

Both enantiomers of 272 were synthesized from (V-methyl-4-piperidinone and 1,3,5-trimethoxybenzene [604], The 3 -hydroxyl was introduced with hydroboration of an alkene and then inversion via oxidation to the ketone and NaBH4 reduction. Introduction of the chromone moiety via acylation of the phenyl ring, followed by O-demethylation, provided 272 [604]. Subsequently, additional analogs of 272 were synthesized and tested for biological activity [609]. 

Oxidation of chromanones. Formation of chromones is achieved under reflux or with ultrasound irradiation. 2-Spiroannulated chromanones give fused-ring systems. 

Chromene ring formation can be effected by oxidative cyclisation of 2-prenylphenols or by reaction of pyrano compounds with DDQ (dichlorodicyanobenzoquinone), by reduction of a chromone with a hydride followed by dehydration with a toluenesulphonic acid, and directly by the use of 1,1-dimethoxy-3,3-dimethyl-3-hydroxypropane. 

Koo et al. have developed an efficient method for the preparation of diverse co-formyl-a,p-unsaturated carbonyl compounds 268 and 273 that relied on the Pb(OAc)4-promoted oxidative ring cleavage of cyclic 1,2-diols 267 and 272, respectively, which in turn can be readily obtained by the 1,2-addition of various nucleophiles to a cx -acetoxy-substituted conjugated cycloalkenones 266 and a-acetoxy cyclohexanone 271. The authors also optimized the conditions for the intramolecular MBH reactions of 268 and 273. The utility of this sequence is demonstrated by the syntheses of chromones 270 and the precursor (274) of the compound containing the 6,8-dioxabicyclo[3.2.1]octane ring (Scheme 1.98). ... 

As natural products do not always have the double bond in the 1,4-pyran ring, there exists the need to have alternative building blocks at different oxidation states. For example, resorcinol 37 was reacted with acrylic acid 38 promoted by BF3 to provide a high yield of chromone 39, which was used to prepare a cannabinoid plant extract. ... 

Oxidation of a methyl side chain is not an attractive route to chromone-2-carboxylic acids because of the ease with which the pyrone ring is attacked by oxidising agents to form salicyclic acid or its derivatives [112]. When 2,3-dimethylchromone is oxidised [113] with selenium dioxide, the main product (57 per cent yield) is the 2-aldehyde (25) a small amount of the 2-carboxylic acid (26) is formed simultaneously. The aldehyde (25) may be oxidised to the carboxylic acid by chromium trioxide in cold acetic acid. 

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