Phenols aromatic hydroxylation

H2O2 in the presence of HE/BE acts as an effective and economical reagent for aromatic hydroxylation (163). Hydroxylations of phenols and amines in similar high acidity media are very effective (163). Xylenes were hydroxylated by bis(trimethylsilyl) peroxide and AlCl in poor yields (164). 

It would not be unreasonable to suggest that the dipole moment of the phenolic system has a negative skew toward the aromatic hydroxyl and that the electronic repulsion of these groups in an ortho-ortho situation greatly reduces the likelihood... 

In a phenol, a hydroxyl group is attached directly to an aromatic ring. The parent compound, phenol itself, Cr,HsOH (4), is a white, crystalline, molecular solid. It was once obtained from the distillation of coal tar, but now it is mainly synthesized from benzene. Many substituted phenols occur naturally, some being responsible for the fragrances of plants. They are often components of essential oils, the oils that can be distilled from flowers and leaves. Thymol (5), for instance, is the active ingredient of oil of thyme, and eugenol (6) provides most of the scent and flavor of oil of cloves. 

In a related procedure, even benzene and substituted benzenes (e.g., PhMe, PhCl, xylenes) can be converted to phenols in good yields with sodium perborate F3CS020H. " Aromatic amines, N-acyl amines, and phenols were hydroxylated with H2O2 in SbFs—HF. Pyridine and quinoline were converted to their 2-acetoxy derivatives in high yields with acetyl hypofluorite AcOF at -75°C. ... 

Endogenous or exogenous aromatic compounds such as phenols and phenolic acids react extremely rapidly with OH radicals to form a mixture of hydroxylated products (Halliwell et /., 1988). Indeed, aromatic hydroxylation serves as an efiective method for evaluating OH radical activity both in vitro (Moorhouse et al., 1985 Grootveld and Halliwell, 1986a) and in vivo (Grootveld and Halliwell, 1986b). 

The concept of microbial models of mammalian metabolism was elaborated by Smith and Rosazza for just such a purpose (27-32). In principle, this concept recognizes the fact that microorganisms catalyze the same types of metabolic reactions as do mammals (32), and they accomplish these by using essentially the same type of enzymes (29). Useful biotransformation reactions common to microbial and mammalian systems include all of the known Phase I and Phase II metabolic reactions implied, including aromatic hydroxylation (accompanied by the NIH shift), N- and O-dealkylations, and glucuronide and sulfate conjugations of phenol to name but a few (27-34). All of these reactions have value in studies with the alkaloids. 

FIGURE 4.78 Mechanistic pathways for aromatic hydroxylation by concerted addition of oxene, pathway 1, or by stepwise addition of oxene, pathway 2. Pathways 2, 3, and 4 describe the formation of phenol that bypasses the arene oxide intermediate. 

Several syntheses exist for vanillin. A process recently developed by Rhodia seems to be superior [11]. The process (Scheme 5.2) involves four catalytic steps starting from phenol aromatic ring hydroxylation, O-methylation, hydroxymethyl-ation, and oxidation. The process combines elegance and precision in organic synthesis. 

The incorporation of vanadium(V) into the framework positions of silicalite-2 has been reported by Hari Prasad Rao and Ramaswamy . With this heterogeneons oxidation catalyst the aromatic hydroxylation of benzene to phenol and to a mixtnre of hydroqninone and catechol conld be promoted. A heterogeneons ZrS-1 catalyst, which has been prepared by incorporation of zirconinm into a silicalite framework and which catalyzes the aromatic oxidation of benzene to phenol with hydrogen peroxide, is known as well in the literature. However, activity and selectivity were lower than observed with the analogous TS-1 catalyst. 

Polymers with hydroxyl groups undergo typical reactions of alcohols. Those with aromatic hydroxyl groups, such as phenolic resins, are attacked by aqueous alkaline solutions. 

The NIH shift has been found to occur during aromatic hydroxylations catalyzed by enzymes present in plants, animals, fungi and bacteria. It is thus evident that the acid catalyzed (or spontaneous) isomerization of oxepins-arene oxides is a very important type of in vivo reaction. It should be emphasized that the NIH shift may occur under either acid-catalyzed or neutral (spontaneous) conditions (76ACR378). The direct chemical oxidation of aromatic rings has also yielded both phenols (obtained via the NIH shift) and arene oxides (80JCS(P1)1693>. 

Polyphenols can act as antioxidants by a number of potential pathways. The most important is likely to be by free radical scavenging, in which the polyphenol can break the radical chain reaction. Polyphenols are effective antioxidants in a wide range of chemical oxidation systems, being capable of scavenging peroxyl radicals, alkyl peroxyl radicals, superoxide, hydroxyl radicals, nitric oxide and peroxynitrate in aqueous and organic environments [121]. This activity is due to the ability of donating an H atom from an aromatic hydroxyl group to a free radical, and the major ability of an aromatic structure to support an unpaired electron by delocalization around the 7i-electron system. Phenolic acids... 

Aromatic hydroxylation. Aromatic hydroxylation such as that depicted in Figure 4.3 for the simplest aromatic system, benzene, is an extremely important bio transformation. The major products of aromatic hydroxylation are phenols, but catechols and quinols may also be formed, arising by further metabolism. One of the toxic effects of benzene is to cause aplastic... 

The formation of sulfate esters is a major route of conjugation for various types of hydroxyl group, and may also occur with amino groups. Thus, substrates include aliphatic alcohols, phenols, aromatic amines, and also endogenous compounds such as steroids and carbohydrates (Figs. 4.56 and 4.57). 

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