Hydroxylation, aromatics phenol, hydroquinone/catechol

Aromatic hydroxylation such as that depicted in figure 4,3 for the simplest aromatic system, benzene, is an extremely important biotransformation. 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 anaemia, which is believed to be due to an intermediate metabolite, possibly hydroquinone. As a result of further metabolism of epoxide intermediates (see below), other metabolites such as diols and glutathione conjugates can also... 

Aromatic species which are activated for electrophilic substitution may be hydroxylated in the presence of strong acids. The largest single application of this technology is for the hydroxylation of phenol to hydroquinone and catechol using a mixture of perchloric and phosphoric acids as catalysts.468 As the products are more readily oxidized compared with the substrate, it is important to limit the conversion of the phenol to prevent over-oxidation to tars. 

The hydroxylation of benzene on TS-1 produces phenol as the primary product. Conversion is generally kept low, because introduction of a hydroxyl group activates the aromatic nucleus to further oxidation to hydroquinone, catechol, and eventually to tarry products (Eq. 2). Acetone, methanol, 2-butanone or just water are suitable reaction media [2,16,17]. In aqueous solution, benzoquinone was also found, in appreciable amounts, among the products. Hydroxylation of benzene with a mixture of hydrogen and oxygen, an in situ source of hydrogen peroxide, can be achieved on Pd-containing TS-1 [18]. This is, in principle, an easier route to phenol than that based on the preformed oxidant [19]. In practice, it proved less effective, because of faster catalyst decay (maximum TON... 

It has been widely reported during the last years that TS-1 was very active and selective in the oxidation of aromatics using H2O7 as the oxidant [61. In particular, it was successfully used for the hydroxylation of phenol into a mixture 01 catechol (the ortho isomer) and hydroquinone (the para isomer) and the hydroxylation of toluene into a mixture of cresols [ 1] according to the scheme ... 

Starting from Benzene. In the direct oxidation of benzene [71-43-2] to phenol, formation of hydroquinone and catechol is observed (64). Ways to favor the formation of dihydroxybenzenes have been explored, hence CuCl in aqueous sulfuric acid medium catalyzes the hydroxylation of benzene to phenol (24%) and hydroquinone (8%) (65). The same effect can also be observed with Cu(II)—Cu(0) as a catalytic system (66). Efforts are now directed toward the use of Pd° on a support and Cu in aqueous acid and in the presence of a reducing agent such as CO, H2, or ethylene (67). Aromatic... 

The incorporation of vanadium(V) into the framework positions of silicalite-2 has been reported by Hari Prasad Rao and Ramaswamy469. With this heterogeneous oxidation catalyst the aromatic hydroxylation of benzene to phenol and to a mixture of hydroquinone and catechol could be promoted. A heterogeneous ZrS-1 catalyst, which has been prepared by incorporation of zirconium 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. 

Hydroxyl radical generated from hydrogen peroxide in the presence of iron(II) salts hydroxylates most aromatic centres, and indeed a phenol hydroxylation process based on this chemistry was operated for nearly a decade.471 The process ran at similar conversions to the acid-catalysed route mentioned above, however selectivity to dihydroxybenzenes was somewhat lower, and some resorcinol was formed along with catechol and hydroquinone. 

Conversely, nucleophilic molecules Nu) [Lewis bases e.g., catechols, hydroquinones, phenols, alcohols, and thiols (and their anions) aromatic hydrocarbons and amines (benzene, toluene, pyridine, bipyridine, etc.)] can be oxidized (1) by direct electron-transfer oxidation [Eq. (161)] [with the electron coming from the Highest-Occupied-Molecular-Orbital (HOMO)] or (2) by coupling with the oxidation product of H2O (or HO ), hydroxyl radical (HO ) [Eq. (162)]. 

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