Ethyl chromanones

The carbanion formed when chromanone is treated with a base such as sodium methoxide reacts with ethyl formate to give the 3-hydroxymethylene derivative (S95) and such compounds have been used as intermediates (72JHC1341,70IJC203). When treated with isopentyl nitrite, chromanones usually give the 3-isonitroso derivative but this reaction occasionally behaves anomalously without obvious reason. For example, 7-methoxychromanone is readily converted into its 3-isonitroso derivative (596), but with 7-hydroxychromanone the reaction fails <77HC(31)207). 

Chromanone and its isomer isochroman-4-one (623) add ethyl diazoacetate at the carbonyl group and the resulting compound undergoes ring enlargement on treatment with mineral acid. The benzoxepin-4(3H)-one (624) is obtained on heating with acid (79JCR(S)142). 

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. 

A 2,2-disubstituted chromanone results from the condensation of o-hydroxyacetophenone with diethyl oxalate. The initially formed 1,3-diketone cyclizes spontaneously to ethyl 2-hydroxy-4-oxochroman-2-carboxylate (77LA1707). The enolate also reacts with aliphatic ketones to give 2,2-disubstituted chroman-4-ones via the diol (79TL3685). 

The synthesis of 3-methylsulfinylchroman-4-one (600) from ethyl salicylate follows a related pathway (72JHC171), whilst the triketone (601), derived from pentane-2,4-dione and the benzoate ester, exists as the substituted chromanone, a cyclic hemiacetal (81JOC2260). 

Expansion of the pyrone ring of chromanones has been achieved by reaction with ethyl diazoacetate and BuLi at —78°C [to produce the a-diazo-ester (154)] followed by acid-catalysed conversion, at room temperature, into the benzoxepin (155). De-ethoxycarbonylation led to the parent 2,3-dihydro-l-benzoxepin-4-(5jF/)-one (156). By a similar sequence, isochroman-4-one (157) was converted into the hitherto unknown l,5-dihydro-2-benzoxepin-4(3H)-one (158). ... 

Ethyl-5,7-dihydroxy-2-methyl-4-chromanone, see E-30148 12-Ethyl-4,11-dihydroxy-3,5,7,11-... 

The products of catalytic reduction of chromone-2-carboxylic acids or esters depend partly on the catalyst used, the amount of hydrogen present and the conditions of reaction. Ethyl chromone-2-carboxylate is reduced (in 86 per cent yield) to the corresponding chromanone in the presence of Raney nickel and hydrogen at a pressure of 50 Ib/in [184]. The 5-hydroxy analogue is similarly reduced at 80°C and 30 Ib/in in 44 per cent yield [8]. A nitro group on the benzene ring is more readily hydrogenated than the pyrone double bond (10 atmospheres, platinum-charcoal or palladium-charcoal catalyst) [24,40]. 

Even on prolonged hydrogenation under these conditions, only 23 per cent of the product was the 2,3-dihydro compound. When Raney nickel (p. 90) or platinum oxide [159] is present, reduction of the double bond at the 2,3-positions frequently occurs. When ethyl 6-chlorochromone-2-carboxylate was reduced with zinc dust and acetic acid, a dimeric chromanone was obtained [25a]. Hydrogenolysis of the chlorine and reduction of the pyrone ring occurred with hydrogen and palladium-charcoal [25a]. 

Hydrolysis methods for mono[ C]nitriles and the spectrum of chemical transformations of the resulting [l- C]carboxylic acids differ little from those for their unlabeled counterparts, so that the synthesis of [l- C]tetralones 42 and [l- " C]indanones 46 from w-arylalkyl [ C]nitriles will suffice as examples (Figure 7.11). Acid-catalyzed hydrolysis of 4-phenylbutyro[ C]nitrile followed by polyphosphoric acid-mediated cyclization of the resulting phenyl[l- C]butanoic acid converted it into 42 in 89% radiochemical yield. Sequential bromination and oxime formation provided the a-bromooxime 43, which upon treatment with polyphosphoric acid underwent a Beckman rearrangement to provide the ring-expanded tetrahydro-2H-l-[2- C]benzazepine-2-one derivative 44- This was a key intermediate for the preparation of a series of labeled ACE inhibitors" . The acid-catalyzed cyclization of a mixture of 3-(2-hydroxyphenyl[l- " C]propionic acid and its ethyl ester, prepared by treatment of the propio[ " C]nitrile with ethanolic HCI proved to be a two-step sequence. In the first step, 2- [2- " C ]chromanone I4SI was formed and had to be submitted to... 

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