O-hydroxyacetophenones

C. Insoluble in water, soluble in organic solvents. Flavone occurs naturally as dust on the flowers and leaves of primulas. It has been prepared from o-hydroxyacetophenone and benzaldehyde. 

The sulfonate ester of o-hydroxyacetophenone oximes, when treated with pyridine, are similarly converted into a benzoxazole, but cyclize to a 1,2-benzisoxazole when treated with aqueous KOH <73JCS(P1)2220, 71T711). 

Heating of the ( )-oximes of o-hydroxyacetophenones produced 1,2-benzisoxazoles as the predominant product, while thermolysis of the (Z)-oximes yielded only minor amounts of 1,2-benzisoxazoles 67AHC(8)277, 73IJC541). 

The mechanism of the K-R reaction has been studied by several groups. " However, the mechanism proposed by Baker and Szell appears to be the most likely pathway. Szell and coworkers agreed with the original mechanism postulated by Baker based on product isolation, spectroscopy and kinetic studies. The o-hydroxyacetophenone 4 is first acylated... 

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. 

In the area of medicinal chemistry, Haemers and coworkers synthesized a series of 4 -hydroxy-3-methoxyflavones that exhibited antiviral activity against poliomyelitis and rhinoviruses. A representative number of compounds is shown below. First, O-hydroxyacetophenones 61 were converted to the corresponding flavones 64 using standard conditions in yields of 74-92%. Cleavage of the benzyloxy groups of 64 was then achieved under acidic conditions to deliver the requisite flavones 65. 

On the other hand, 1,1,1-trisubstituted alkanes behave similarly to aldehydes, yielding pyrjdium salts (128) with identical substituents in positions 2 and 6. Thus, Dorofeenko and co-workers condensed 2 moles of acetophenone with 1 mole of benzotrichloride in the presence of perchloric acid obtaining 2,4,6-triphenjdpjTylium perchlorate with 1 mole of ethyl orthoformate, they obtained 2,6-diphenyl-pyrylium perchlorate (57) from o-hydroxyacetophenone, ortho-formic ester and perchloric acid, 4-ethoxybenzopyrylium perchlorate was formed. 

In much the same vein, condensation of the difunetional o-hydroxyacetophenone 64 with diethyl... 

The Knoevenagel reaction between o-hydroxyaryl aldehydes and ketones and substituted acetonitriles affords high yields of 3-substituted coumarins in aqueous alkaline media <96H(43)1257>, whilst 4-hydroxycoumarins have been elaborated to pyrano [3,2-c]benzopyran-5-ones by reaction with aromatic aldehydes and malononitiile <96P148>. The imine (10) resulting from the complex reaction of o-hydroxyacetophenone with malononitrile undergoes a 1,5-tautomeric shift in solution <96JCS(P1)1067>. 

The immobilization of metal catalysts onto sohd supports has become an important research area, as catalyst recovery, recycling as well as product separation is easier under heterogeneous conditions. In this respect, the iron complex of the Schiff base HPPn 15 (HPPn = iVA -bis(o-hydroxyacetophenone) propylene diamine) was supported onto cross-linked chloromethylated polystyrene beads. Interestingly, the supported catalyst showed higher catalytic activity than the free metal complex (Scheme 8) [50, 51]. In terms of chemical stability, particularly with... 

J>-Benzoqumone, 35, 26 Benzoylacetanilide, 37, 2 Benzoylacetic acid, ethyl ester, 37, 3 Benzoylacetic acid, ethyl ester, 37, 32 Benzoylation, of o-hydroxyacetophenone, 32, 72... 

The reaction of Zr(OPr ) with the Schiff bases acetylacetone-2-hydroxy-alkylimine, N-[(3-hydroxy-2-naphthyl)methylene]-2-hydroxyalkylamine, and o-hydroxyacetophenone-2-hydroxyalkylimine (HL) affords the polymeric Zr(OPr )2L and ZrL2 compounds. N.m.r. and i.r. spectral studies indicated that the N atom of the Schiff base is co-ordinated in these compounds. 

Upon oxidation with IBD, a series of o-hydroxyacetophenones and related compounds 57 give the corresponding 2-methoxycoumaran-3-ones 59 [84JCS(CC)1342] (Scheme 19). These reactions probably occur via intramolecular participation of the ortho hydroxy group, which attacks the a-carbon of the intermediate 58 to yield the intermediate product 58a. A similar reaction occurs when /3-diketones 60 are oxidized with IBD-KOH/MeOH,... 

A. o-Benzoyloxyacetophenone. In a 100-ml. conical flask fitted with a calcium chloride drying tube are placed 13.6 g. (12 ml., 0.1 mole) of o-hydroxyacetophenone,2 21.1 g. (17.4 ml., 0.15 mole) of benzoyl chloride, and 20 ml. of pyridine (Note 1). The temperature of the reaction mixture rises spontaneously, and when no further heat is evolved (about 15 minutes) the mixture is poured with good stirring into 600 ml. of 3% hydrochloric... 

Other methods of preparing flavone include the action of ethanolic alkali on 2 -acetoxy-a,/3-dibromochalcone 7 Claisen condensation of ethyl o-ethoxybenzoate and acetophenone, and cyclization of the resulting 1,3-diketone with hydriodic acid 8 and treatment of 3-bromoflavanone with potassium hydroxide in ethanol.9 Flavone has also been prepared from ethyl phenyl-propiolate by condensation with sodium phenoxide and subsequent cyclization with phosphorus pentachloride in benzene 10 by fusing o-hydroxyacetophenone with benzoic anhydride and sodium benzoate 11 by the dehydrogenation of 2 -hydroxychal-cone with selenium dioxide 12 and by the action of alkali on flavylium chloride.13... 

The above process is applicable to almost all hydroxyalde-hydes in which the hydroxyl and carbonyl groups occupy ortho or para positions relatively to each other 1 in the latter case derivatives of hydroquinone are produced. When the hydroxyl and carbonyl groups occupy the meta position with respect to each other, no reaction takes place, as is also the case with certain ortho and para compounds containing nitro groups and iodine atoms. o-Hydroxyacetophenone and />-hydroxyaceto-phenone are also capable of yielding catechol and hydroquinone respectively under the above conditions. 

Strong intramolecular hydrogen bonding occurs in o-hydroxyacetophenone. The resulting absorption at... 

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