Ethyl acetate 4-hydroxyacetophenone

Acetamido-2-hydroxyacetophenone (19.3 g), allyl bromide (12.1 ml) and hydrous potassium carbonate (21.5 g) were stirred in dry dimethylformamide (250 ml) at room temperature for 24 hours. The reaction mixture was poured into water and the product was extracted with ethyl acetate. The organic solution was then washed well with water dried over magnesium sulphate and evaporated to dryness. The sub-title product was obtained as buff coloured solid (20.5 g). The structure of the product was confirmed by NMR and mass spectroscopy. 

Preparation by bromination of 2,4-dimethoxy-6-hydroxyacetophenone with cupric bromide in refluxing chloroform-ethyl acetate mixture [1845,2922], (62%) [2922]. 

Preparation by catalytic hydrogenation of 3-allyl-2,4-di-hydroxyacetophenone using palladium chloride as catalyst in ethanol (quantitative yield) [3182] or Raney nickel in ethyl acetate [2671]. 

Preparation by catalytic hydrogenation of 2-allyl-3,6-di-hydroxyacetophenone using palladised strontium carbonate catalyst [3240] or Raney nickel (60%) [3181] in ethyl acetate. 

Preparation by bromination of 5-bromo-2-hydroxyacetophenone with cupric bromide in reflnxing chloroform-ethyl acetate mixture [4390,4407], (50%) [4407]. 

A modification of the K-R reaction was introduced by Mozingo. This method involved reacting an o-hydroxyacetophenone with an ester in the presence of metallic sodium to form a 1,3-diketone. Treatment of the diketone with an acid then delivered the chromone via an intramolecular cyclization reaction. This method was applied to the preparation of 2-ethylchromone (21). 0-hydroxyarylketone 22 was allowed to react with ethyl propionate (23) in the presence of sodium metal.The resulting sodium enolate was then quenched with acetic acid to deliver the 1,3-diketone 24. Upon heating 24 in glacial acetic acid and hydrochloric acid, 2-ethylchromone (21) was delivered in 70-75% overall yield. 

Wu and co-workers [77] have developed a novel, simple and efficient method for the synthesis of 2,4,5-triaryl-5//-chromeno[4,3-h]pyridines 37 under microwave radiation via a three-component cascade reaction of 2-hydroxyacetophenone, an aromatic aldehyde and ammonium acetate catalyzed by 2-l -methylimidazolium-3-yl-l-ethyl sulfate. When an insufficient amount of (or no) catalyst was used, solely the corresponding chalcone was formed. Nine new bonds and two new rings are generated in a one-pot process with water as the only byproduct (Scheme 26). 

Cyclodextrins form inclusion compounds in aqueous solution with various molecules which may then exhibit modified reactivity (see reference 185 above). It was reported in 1975 that the presence of p-cyclodextrin modified the ortho para ratio of hydroxyacetophenones formed photochemically from phenyl acetate,and the photoinduced rearrangements of acetanilide, ben-zanilide, and ethyl phenyl carbonate under similar conditions are now reported. In each case the para rearrangement isomer is favoured, and this is rationalized in terms of the aromatic nucleus being bonded into the cyclodextrin cavity such that the ortho and weta positions are shielded whDe the para position is accessible. This proposal is supported by observations that para but not ortho disubstituted arenes are well bonded into p-cyclodextrin cavities. The by-product formation of aniline from the amides and of phenol from the carbonate is also markedly reduced for reactions in the presence of the cyclodextrin. 

The use of ethyl [2-13C]acetoacetate instead of diethyl [2-t3CJmafonafe in the condensation reaction with 4H-pyran-4-one afforded ethyl 4-hydroxy[1 -13C]benzoate in 87% yield. In this case, 1.1 equiv of 4H-pyran-4-one and 1.1 equiv of potassium tert-butoxide were optimal. The addition of catalytic amounts of the base was not satisfactory. Ethyl [2-13C]acetoacetate was prepared from ethyl (2-13C]acetate as described for diethyl [2-13C]matonate.16 The maximum yield for this reaction on a 10-mmol scale was only 70% after distillation. 4H-Pyran-4-one reacted with nitromethane and potassium tert-butoxide (each 1.1 equiv) to afford 4-nitrophenol in 75% yield after purification by flash chromatography. This gives easy access to 4-nitro[4-13C]phenol. With 2,4-pentanedione, the condensation with 4H-pyran-4-one under the same reaction conditions gave 4-hydroxyacetophenone in 45-50% yield after purification. 

Preparation from 3-chloro-2-hydroxyacetophenone in acetic add solution by introduction of the chlorom-ethyl group into aromatic ring by treatment with formaldehyde and hydrogen chloride in the presence of zinc chloride (44%) [2490] (Blanc [2490] reaction). 

Preparation by bromination of 4-hydroxyacetophenone in acetic acid (63%) [4422] or in a mixture of ethyl ether and chloroform [4413] according to [4414]. Preparation by Fries rearrangement of phenyl bromoacetate with aluminium chloride without solvent between 120° and 140° (40%) [4415], (30%) [4416]. Preparation by reaction of tetrabutylammonium tribromide, benzyltrimethylam-monium tribromide or phenyltrimethylammonium tribromide on 4-hydroxyacetophenone in tetrahydrofuran [4403]. 

While not purported to be a photoremovable protecting group, the study by Anderson and Reese on substituted phenacyl chlorides did reveal an interesting photochemical rearrangement for certain members of the series, particularly the report that the Favorskii-like rearrangement ofp-hydroxyphenacyl chloride (27) in 1% aqueous ethanol gave two major photoproducts p-hydroxyacetophenone (28) and ethyl p-hydroxyphenyl acetate (29), as shown in Eq. (69.10). The authors proposed a spiro intermediate 30. 

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