Chromone 6-acetyl-3-

Sen and Kakaji synthesized a series of 4-butyrylnaphthocoumarins 48 from l-butyryl-2-naphthols 49 using acetic anhydride and two homolog anhydrides in excellent yields. They also showed that l-propionyl-2-naphthols and l-acetyl-2-naphthols could be converted to their corresponding coumarins using the same three anhydrides. However, l-acetyl-2-naphthol in the presence of acetic anhydride and sodium acetate gave a chromone not a coumarin. 

The synthesis of chromones by the Kostanecki-Robinson method frequently yields a 3-acetylchromone. This acetyl group forms a 1,3-diketone with the pyran carbonyl group and is therefore labile in an alkaline medium. Treatment with aqueous carbonate or other base removes such groups but has no effect on other acyl substituents, for example the 6-acetyl of 3,6-diacetyl-2-methylnaphtho[l,2- ]pyran-4-one (516). 

Not unexpectedly, a substituent on the acetyl group of the 2-hydroxyacetophenone has an effect on the condensation, though successful preparations of 3-substituted chromones have been achieved. A neat alternative approach to such chromones involves alkylation of the intermediate diketone and subsequent cyclization (34JCS1311). 

A number of 2,3-fused chromones have been prepared from ethyl chloroformate and acetylsalicylic acid, a source of the mixed anhydride of formic and salicylic acids, and piperidinocycloalkenes (69JCS(C)935). A plausible mechanism is outlined in Scheme 165. It has not proved possible to isolate the chromanone (460) but the formation of 3-acetyl-2-methylchromone from 2-pyrrolidinopropene lends support to the intermediacy of the chromanone. The migration of the acyl group from oxygen to carbon is supported by the synthesis of 3-benzoyl-2-methylchromone rather than 3-acetylflavone from benzoylsalicylic acid and the pyrrolidinopropene. 

Treatment of a hydroxy carbaldehyde precursor with chloroacetone in refluxing THF in the presence of potassium carbonate and 18-crown-6 resulted in the formation of the 2-acetyl furo-chromone (52) in 53% yield (Equation (25)) <84TL2953>. 

A series of new substituted oestradiols has been synthesized. The reaction of oestradiol with acetyl chloride gave the 2-acetyl derivative (133a). Condensation with ethyl formate (see Scheme 11), followed by brief exposure to acid, afforded the steroidal chromone (134). Whereas treatment of (134) with hydrazine hydrate provided the 3 -phenylpyrazole (135), reaction with hydroxylamine yielded a mixture of the 5 -phenylisoxazole (136) and of the isomeric 3 -phenyl-isoxazole (137). When the oxime (133b) was allowed to react with benzenesul-phonyl chloride in pyridine solution, the methylbenzoxazole (138) was obtained. 

Diformylation and cyclization of the boron trifluoride complex (59) of l-acetyl-2-hydroxynaphthalene surprisingly gave the peri-cyclized, phe-nalenone (60) as the major product, rather than the expected chromone (61).46... 

Chromone derivatives, in particular 2-spiro-chroman-4(lF/)-ones, are ubiquitous in nature and possess various biological activities which include antiarrhythmic, anti-HIV, antidiabetic, acetyl-CoA carboxylase (ACC) inhibitor, vanilloid receptor antagonist, growth hormone secretagogues, histamine receptor antagonist, and... 

In the metabolism study (29, 30, 31) the following seven metabolites, 6-(1-hydroxyethyl)-3-(Ijl-tetrazol-5-yl)-chromone (1 ), 6-acetyl-3-(lH-tetrazol-5-yl)chromone (I7)j 6-(2-hydroxyethyl)-3-(lH-tetrazol-5-yl)chromone (l ), (l,2-dihydroxyethyl)-3-( Ifl-tet razo 1 -5-y 1) chromone (1 ), glucuronide (20) (the structural elucidation is described below), 5 ethylsalicylic acid ( ) and 3-carboxy-4-hydroxy-phenylacetic acid ( ), were identified in the urine of rats, guinea pigs, rabbits, dogs and monkeys. These seven compounds were synthesized and used as reference compounds to unequivocally establish the structures of the urinary metabolites, and to allow evaluation of their antiallergic activity (32). The synthetic routes are shown below (Figure 4). 

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]. 

Benzaldehyd> 4 azo 4) benzoes ine-athyleeter 16, 236. nLm -Azozyaoetbphenon 16, 643. p.p -Azoxyaoetopnenon 16, 643. 2-Methyl>3 acetyl-5.6>benzo Chromon dionm 17II502. 

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