Substituents Located on the Hydroxylated Ring

Martin, Aromatic Hydroxyketones Preparation and Physical Properties, 

SM was obtained by Friedel-Crafts acylation of 2,3-dichloroanisole with benzoyl chloride in the presence of aluminium chloride in methylene chloride [475], first at 0° for 30 min, then at r.t. for 6 h (42%) [477] or in ethylene dichloride for 2 h [476]. 

QH Preparation by Fries rearrangement of 2,5-diflu- — / orophenyl benzoate with aluminium chloride at 

SM was prepared by Friedel-Crafts acylation of benzene with 2-bromo-3,5-dinitrobenzoyl chloride in the presence of aluminium chlwide (97%, m.p. 153-154°). Refer to Chem. Abstr., 20,1229 (1926).  

Preparation by demethylation of 3-bromo-4-methoxy-benzophenone (SM) with 48% hydrobromic acid in refluxing acetic acid. SM was prepared by reaction of bromine with 4-methoxybenzophenone in the presence of sodium acetate in acetic acid at 100° for 6 h [140]. 

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Substituents Located on the Hydroxylated Ring Phenyl(2,3,5-trifluoro-4,6-dihydroxyphenyl)methanone... 

The resulting phenoxonium ion 15, cited in Scheme 2, is attacked by a variety of nucleophiles to yield three cyclohexadienones (64, 65 and 66), as shown in Scheme 12, where X, X, Y and Z are suitable functional groups such as hydrogen atom, alkyl, aryl, alkoxyl and/or hydroxyl group. Usually, these three compounds are competitively formed depending upon the substituents and their locations on the benzene ring. In the... 

Table 2-8 illustrates several items that must be kept in mind when selecting. substituents to be evaluated in terms nf the type of factors that influence a biological response. Fur electronic parameters such as aromatic ring is important because of resonance versus inductive effects. Notice the twofold differences seen between and fur the three aliphatic substituents and iodo. and scvcralfold difference for methuxy, amino. Huoru, and phenolic hydroxyl. 

The mass spectra (Section II, D) indicated that the phenolic function was located in the cularine half of the molecule, whereas a comparison of the NMR spectra of cancentrine (1) and its 0-acetate (3) indicated that there is a proton para to a phenolic hydroxyl group (6) and hence the latter must be placed at C-20. This assignment was confirmed by observed nuclear Overhauser effects (NOE) of 25, 25, and 24%, respectively, in three aromatic signals when the methoxyl resonances of cancentrine were saturated in turn. Such a result is possible only if each of the three methoxyl groups is vicinal to an aromatic proton. Since the location of the substituents on the aromatic rings was known from the X-ray structure of 7 this result unambiguously places the hydroxyl group at C-20 (3). 

In some instances, particularly in hydroxyla-tions meta to a halide substituent, the hydrogen on the hydroxylated carbon is quantitatively lost (i.e., there is no NIH shift), and a small deuterium kinetic isotope effect is observed These hydroxylations could result from direct oxygen insertion into the C-H bond, as in a true hydrox-ylation mechanism, but they are more likely to result from oxidation of the aromatic ring without the formation of a discrete epoxide intermediate. Isotope effect studies with deuterated benzenes bearing a variety of substituents have shed some light on this process A small, normal isotope effect is observed for weta-hydroxylation when deuterium is located meta- to the halogen in chlorobenzene = 1.1-1.3), but a small,... 

The terms cis and irons correspond respectively to the hydrogens of the hydroxyl group and of the substituent being located on the same or opposite sides of the ring plane. 

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