Hydroxylation, of phenols

A promising and cleaner route was opened by the discovery of titanium silica-lite-1 (TS-1) [1,2]. Its successful application in the hydroxylation of phenol started a surge of studies on related catalysts. Since then, and mostly in recent years, the preparation of several other zeolites, with different transition metals in their lattice and of different structure, has been claimed [3]. Few of them have been tested for the hydroxylation of benzene and substituted benzenes with hydrogen peroxide. Ongoing research on suppoi ted metals and metal oxides has continued simultaneously. As a result, knowledge in the field of aromatic hydroxylation has experienced major advances in recent years. For the sake of simplicity, the subject matter will be ordered according to four classes of catalyst medium-pore titanium zeolites, large-pore titanium zeolites, other transition metal-substituted molecular sieves, and supported metals and mixed oxides. 

Titanium silicalite (TS-1) is a porous crystalline titanium silicalite with the MFI structure, analogous to ZSM-5 [1], Catalytic centers are isolated Ti sites in a silica framework [4]. Unlike Ti02/Si02 with a similar elemental composition but an amorphous structure, TS-1 is an effective catalyst for the selective oxidation of different functional groups with dilute aqueous hydrogen peroxide [2]. The structural properties of lattice Ti sites, the hydrophobicity, and the size of the tridimensional channel system (ca 0.55 nm) are thought to be critical factors in determining the unusual catalytic properties of TS-1. 

The hydroxylation of phenol, developed by Enichem up to the industrial scale, was the event that initially attracted most interest in TS-1 (Eq. 1) [2]. 

The yields, relative to both hydrogen peroxide and phenol, were superior to those of the homolytic and acidic catalysts already used in commercial processes (Table 1) [5,6]. TS-1 enabled the more efficient use of a relatively expensive oxidant and minimized the need for phenol separation/recycle steps. The reaction conditions and the results of a number of studies are given below (Table 2) [2,7-10]. 

Yields and kinetics depend on the type and number of Ti species and the crystal size of the catalyst used. Ti distribution between lattice (selective) and extra-lattice (unselective) sites is, in turn, closely linked to synthesis and characterization procedures, both of which require special thoroughness [4]. Inadequate characterization and, therefore, the impossibility of clear assessment of siting of Ti in the catalyst, is a frequent obstacle to a correct evaluation of the literature, especially early publications. These considerations are of general value, but are central to the hydroxylation of phenol where extra-framework species are a major source of hydrogen peroxide decomposition and radical chain oxidations. The hydroxylation of phenol was indeed proposed by three different groups as an additional test to assess the purity of TS-1 [2, 9, 11]. Van der Pool et al. estimated from Weisz 

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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). 

During the 1980s few innovations were disclosed in the Hterature. The hydroxylation of phenol by hydrogen peroxide has been extensively studied in order to improve the catalytic system as well as to master the ratio of hydroquinone to catechol. Other routes, targeting a selective access to one of the dihydroxyben2enes, have appeared. World production capacities according to countries and process types are presented in Table 1. 

Ca.ta.lysis by Protons. The discovery of hydrogen peroxide hydroxylation of phenol in the presence of strong acids such as perchloric, trifluoromethane-sulfonic, or sulfuric acids allows suppression of all previous drawbacks of the process (18,19). This mode of hydroxylation gives high yields (85% based on H2O2 at phenol conversion of 5—6%). It can be mn without solvents and does not generate resorcinol. Its main advantage rehes on... 

Among the reactions mentioned before, the early industrial applications of TS-1 catalyst were the hydroxylation of phenol (lOOOOton/year) and the... 

The TS-1 catalysed hydroxylation of phenol to a 1 1 mixture of catechol and hydroquinone (Fig. 2.16) was commercialized by Enichem (Romano et ai, 1990). This process offers definite advantages, such as higher selectivities at higher phenol conversions, compared to other catalytic systems. It also illustrates another interesting development the use of solid, recyclable catalysts for liquid phase (oxidation) processes to minimize waste production even further. 

Now, we will consider the major reactions of peroxynitrite with biomolecules. It was found that peroxynitrite reacts with many biomolecules belonging to various chemical classes, with the bimolecular rate constants from 10-3 to 10s 1 mol 1 s 1 (Table 21.2). Reactions of peroxynitrite with phenols were studied most thoroughly due to the important role of peroxynitrite in the in vivo nitration and oxidation of free tyrosine and tyrosine residues in proteins. In 1992, Beckman et al. [112] have showed that peroxynitrite efficiently nitrates 4-hydroxyphenylacetate at pH 7.5. van der Vliet et al. [113] found that the reactions of peroxynitrite with tyrosine and phenylalanine resulted in the formation of both hydroxylated and nitrated products. In authors opinion the formation of these products was mediated by N02 and HO radicals. Studying peroxynitrite reactions with phenol, tyrosine, and salicylate, Ramezanian et al. [114] showed that these reactions are of first-order in peroxynitrite and zero-order in phenolic compounds. These authors supposed that there should be two different intermediates responsible for the nitration and hydroxylation of phenols but rejected the most probable proposal that these intermediates should be NO2 and HO. ... 

The reaction of binuclear copper complexes with oxygen as models for tyrosinase activity was also markedly accelerated by applying pressure (106408 ). Tyrosinase is a dinuclear copper protein which catalyses the hydroxylation of phenols. This reaction was first successfully modeled by Karlin and co-workers (109), who found that an intramolecular hydroxylation occurred when the binuclear Cu(I) complex of XYL-H was treated with oxygen (Scheme 5). 

Cytochrome P4502E1, also microsomally located, catalyzes the hydroxylation of phenol to form hydroquinone (and to a much lesser extent catechol), which is then acted upon by the phase II enzymes (Benet et al. 1995 Campbell et al. 1987 Gut et al. 1996 McFadden et al. 1996). All three enzyme systems are found in multiple tissues and there is competition among them not only for phenol but for subsequent oxidative products, like hydroquinone. As a consequence, the relative amount of the products formed can vary based on species, dose and route of administration. In vivo, the gastrointestinal tract, liver, lung, and kidney appear to be the major sites of phenol sulfate and glucuronide conjugation of simple phenols (Cassidy and Houston 1984 Powell et al. 1974 Quebbemann and Anders 1973 ... 

Subrahmanyam VV, Kolachana P, Smith MT. 1991. Hydroxylation of phenol to hydroquinone catalyzed by a human myeloperoxidase-superoxide complex Possible implications in benzene-induced myelotoxicity. Free Radic Res Comms 15 285-296. 

Transition metal complexes encapsulated in the cavities of zeolites and meso-porous materials exhibit enhanced catalytic activity, compared to their neat analogs. " We had earlier found that Cu(II)-acetate exhibited enhanced regiose-lective orf/zo-hydroxylation of phenols using atmospheric oxygen as the oxidant on encapsulation in molecular sieves Y, MCM-22 or VPI-5. Rao et al. had also found a similar enhancement for encapsulation in Al-MCM-48. 

TABLE 11.12. Hydroxylation of phenol using molecular oxygen as the oxidant (pH = 6.5, temperature = 298 K, reaction time = 19 h) ... 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

Tyrosinase. This enzyme is found in numerous organisms ranging tom bacteria and fungi to plants and animals. The best characterized tyrosinases are those tom mushrooms and tom N. crassa (11-14). The reactions catalyzed by tyrosinase are the hydroxylation of phenols to give catechols and the subsequent oxi tion of catechols to give o-quinones. 

Recently, the preparation of metallosilicates with MFI structure, which are composed of silicone oxide and metal oxide substituted isomorphously to aluminium oxide, has been studied actively [1,2]. It is expected that acid sites of different strength from those of aluminosilicate are generated when some tri-valent elements other than aluminium are introduced into the framework of silicalite. The Bronsted acid sites of metallosilicates must be Si(0H)Me, so the facility of heterogeneous rupture of the OH bond should be due to the properties of the metal element. Therefore, the acidity of metallosilicate could be controlled by choosing the metal element. Moreover, the transition-metal elements introduced into the zeolite framework play specific catalytic roles. For example, Ti-silicate with MFI structure has the high activity and selectivity for the hydroxylation of phenol to produce catechol and hydroquinon [3],... 

Selective hydroxylation of phenol with hydrogen peroxide was reported on acid zeolite catalysts [91-92]. Peroxonium ions, formed by H2O2 protonation, are the oxidizing species. When the reaction is carried out on a faujasite catalyst, a mixture of hydroxybenzenes and tars is obtained [91]. In the presence of H-ZSM-5 on the other hand, no tar formation was mentioned (which does not necessarily mean that it was absent) and p-selectivities close to 100% were reported for the hydroxylation [92]. These superior selectivities reflect the shape selective properties of ZSM type zeolites. 

The isomer distribution in the hydroxylation of phenol, anisole and toluene or other aromatics on TS-1 is influenced by the reaction conditions, but is characterized by a tendency towards p-selectivity [105-106]. Furthermore secondary reactions leading to polynuclear aromatic byproducts are minimized. Both phenomena are ascribed to the pore structure of the catalyst, which is isostructural to ZSM-5 [96]. The selectivity for hydroxylation as well as the H2O2 efficiency decrease with increasing conversions as is shown in Figure 14 for the hydroxylation of phenol [106]. 

Figure 14. Hydroxylation of phenol by H2O2 on TS-1 as a function of the feed ratio H202/phenol [106].

Hydroxylation of phenol or phenol ethers with H2O2 on a so called titanozeosilite, has also been reported and is very similar to the TS-1 catalyzed reaction [115]. The essential difference between TS-1 and... 

Analogous to the acid catalyzed hydroxylation of phenol on H-ZSM-5 with hydrogen peroxide [92], benzene and chlorobenzene can be oxidized with dinitrogen oxide on HZSM-5 [125-126]. In the hydroxylation of benzene, the selectivity for phenol is high at conversions below 10%, with selectivities in N2O of about 30%. A small amount of ortho-diphenol or catechol was formed. The hydroxylation of chlorobenzene was also ortho-selective (58%). The reaction was proposed to proceed via scheme 7. 

The production of hydroquinone and catechol by TS-1 catalyzed hydroxylation of phenol with H2O2 appeared competitive with respect to existing industrial processes. A new industrial process has been developed based on TS-1 and a plant for the production of 10,000 tons/y of diphenols has been built in Ravenna, Italy [7], It operates since 1986 with excellent results. A plant for the industrial production of TS-1 has also been built to provide the diphenols plant with the required amount of catalyst. 

Typical examples referring to titanium derivatives are alkoxides with TBHP and titanosilicate (in particular TS-1) in the presence of H202. Based on this latter system, ENICHEM" commercialized a procedure for hydroxylation of phenol to cathecol and hydroquinone. Other activated arenes are also hydroxylated by TS-1 and hydrogen peroxide". Interestingly, for TS-1 catalysis a mechanism similar to that proposed... 

The discovery of titanium substituted ZSM-5 (TS-1) and ZSM-11 (TS-2) have led to remarkable progress in oxidation catalysis (1,2). These materials catalyze the oxidation of various organic substrates using aqueous hydrogen peroxide as oxidant. For example, TS-1 is now used commercially for the hydroxylation of phenol to hydroquinone and catechol (/). Additionally, TS-1 has also shown activity for the oxidation of alkanes at temperatures below 1()0 °C (3,4). 

The catalytic activity of the materials used in this study are shown in Table n. The hydroxylation of phenol produces a mixture of catechol and hydroquinone. The... 

Stack and co-workers recently reported a related jx-rf / -peroxodi-copper(II) complex 28 with a bulky bidentate amine ligand capable of hydroxylating phenolates at - 80 °C. At - 120 °C, a bis(yu,-oxo)dicopper(III) phenolate complex 29 with a fully cleaved 0-0 bond was spectroscopically detected (Scheme 13) [190]. These observations imply an alternative mechanism for the catalytic hydroxylation of phenols, as carried out by the tyrosinase metalloenzyme, in which 0-0 bond scission precedes C - 0 bond formation. Hence, the hydroxylation of 2,4-di-tert-butylphenolate would proceed via an electrophilic aromatic substitution reaction. 

While only tyrosinase catalyzes the ortho-hydroxylation of phenol moieties, both tyrosinase and catechol oxidase mediate the subsequent oxidation of the resulting catechols to the corresponding quinones. Various mono- and dinu-clear copper coordination compounds have been investigated as biomimetic catalysts for catechol oxidation [21,194], in most cases using 3,5-di-tert-butylcatechol (DTBC) as the substrate (Eq. 16). The low redox potential of DTBC makes it easy to oxidize, and its bulky tert-butyl groups prevent un-... 

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