Hydroxyaryl Alkyl Ketones

A Fries rearrangement of phenyl acetate with zirconium tetrachloride in benzene, toluene or xylene in the temperature range 120-170°C has been reported to give 2-hydroxyacetophenone in high yield (ref. 11). 

Phenyl propionate has been converted to 2-propionylphenol in 62% yield by 

A photochemical rearragement of phenyl acetate in hexane solution containing powdered potassium carbonate by irradiation at ambient temperature with a 125 watt medium pressure mercury lamp during 12 hours furnished a 74% yield of 2-hydroxyacetophenone although in the absence of the base the yield dropped to 13% (ref. 13). 

A rapid photochemial method, described as higher-yielding than the conventional Fries rearrangement for phenyl cinnamate, in which a 10 M solution as micelles in lO M aqueous sodium dodecylsulphate was stirred for 

10-12 hours and then irradiated at 254nm for 6 hours under nitrogen in the quartz well of an annular photoreactor (model APQ 40, with a 16w low-pressure mercury lamp), produced a 70% yield of 2-dnnamoylphenol (with 90% conversion) (ref. 14). 

---

Gupta, S. K. Skin whitening compositions based on hydroxyaryl alkyl ketones and their isosteric derivatives. U.S. Pat. Appl. Publ. US 2005271608, 2005 Chem. Abstr. 2005,144,40393. 

Coumarins and Isocoumarins.- Several new or improved syntheses of coumarins have been reported. A new one-pot synthesis under mild conditions promises to be a widely applicable route from salicylaldehydes or 2-hydroxyaryl alkyl (or aryl) ketones (145 R1 = H, alkyl, OH, N02 R2=H, Me or Ph) and trimethylsilylketene... 

The general approach can be enlarged and conditions for condensation made milder by the use of further-activated esters, thus condensation with methyl nitroacetate produces 3-nitro-coumarins, condensations with Wittig ylides " allow orffto-hydroxyaryl ketones to be used ° and the use of diethyl malonate (or malonic acid ) (a 3-ester can be removed by hydrolysis and decarboxylation ), malononitrile, ethyl trifluo-roacetoacetate, or substituted acetonitriles in a Knoevenagel condensation, produces coumarins with a 3-ester, 3-trifluoroacetyl, " 3-cyano, or 3-alkyl or -aryl substituent. Condensation with IV-acetylglycine generates 3-acetylamino-coumarins. ... 

Intramolecular aldol/Perkin type condensation of orf/to-formylaryloxyacetic acids and arylthioacetic esters produces benzofuran- and benzothiophene-2-esters respectively, as illustrated below. The synthesis can be performed in one pot, thus ortfto-hydroxyaryl-aldehydes or -ketones, are 0-alkylated with a-halo-ketones, then intramolecular aldol condensation in situ produces 2-acyl or 2-aroyl-benzofurans. ° For benzothiophenes, the ring-closure substrates can also be obtained via methyl thioacetate displacement of fluoride from orf/to-fluoro-araldehydes. ... 

---