Hydroxylation of aromatics

The most commonly employed reagent for the hydroxylation of aromatic compounds is that consisting of ferrous ion and hydrogen peroxide. The suggestion that hydroxyl radicals are intermediates in this reaction was first made by Haber and Weiss, who proposed the following radical-chain mechanism for the process ... 

In the same spirit DFT studies on peroxo-complexes in titanosilicalite-1 catalyst were performed [3]. This topic was selected since Ti-containing porous silicates exhibited excellent catalytic activities in the oxidation of various organic compounds in the presence of hydrogen peroxide under mild conditions. Catalytic reactions include epoxidation of alkenes, oxidation of alkanes, alcohols, amines, hydroxylation of aromatics, and ammoximation of ketones. The studies comprised detailed analysis of the activated adsorption of hydrogen peroxide with... 

One-step hydroxylation of aromatic nucleus with nitrous oxide (N2O) is among recently discovered organic reactions. A high eflSciency of FeZSM-5 zeolites in this reaction relates to a pronounced biomimetic-type activity of iron complexes stabilized in ZSM-5 matrix. N2O decomposition on these complexes produces particular atomic oj gen form (a-oxygen), whose chemistry is similar to that performed by the active oxygen of enzyme monooxygenases. Room temperature oxidation reactions of a-oxygen as well as the data on the kinetic isotope effect and Moessbauer spectroscopy show FeZSM-5 zeolite to be a successfiil biomimetic model. 

The reaction is carried out using a titanium silicalite-1 (TS-1) zeolite catalyst [30, 122]. This type of catalyst is known to accelerate the selective oxidation of alcohols, epoxidation of alkenes and hydroxylation of aromatics. These reactions have importance for fine-chemical production. 

The uncatalysed p-coumaric acid oxidation led to the formation of intermediates (not shown here) almost similar to those of the catalysed reaction, without formation of dihydroxylated aromatic compounds, such as 3,4- dihydroxybenzaldehyde. This result shows that the catalyst may promote the hydroxylation of aromatic ring by enhancing the formation of hydroxyl radicals in the reaction mixture. 

Hydroxy radicals are intermediates in the reaction of Ti3+ and H2O2 (175). This system is also capable of hydroxylation of aromatics and alkanes but, in contrast to reactions with Fenton s reagent (Fe2+ + H202, reductive, homolytic cleavage, Eq. (11)), only non-chain processes are possible, because Ti4+ is not usually an oxidant. Hence, relatively high selectivities are feasible. 

The hydroxylation of C-H bonds by radicals, in contrast to the case of electrophilic oxidants, leads to alcohols without retention of stereochemical configuration. H202, activated by strong acids (superacids (277), HF-BF3 (272), A1C13 (213), and CF3COOH (214)) have been used for the hydroxylation of aromatic compounds. These acid-catalyzed hydroxylations cannot be applied for aliphatic reactants because the hydroxylated products are more reactive than the starting compounds and, hence, they are oxidized further. 

The hydroxylation of aromatic compounds using microorganisms is more predictable and a number of processes have been adapted to large scale, for example the preparation of 6-hydroxynicotinic acid1781 and (R)-2-(4-hydroxy-phenoxy)propanoic acid1791, important intermediates to pesticides and herbicides respectively. 

Fenton s reagent [H2O2 + Fe(II)] can be used as a redox carrier for the indirect hydroxylation of aromatic... 

Scheme 37 Hydroxylation of aromatic compounds mediated by Fenton s reagent.

Kumar, R., Mukherjee, P., and Bhaumik, A. (1999) Enhancement in the reaction rates in the hydroxylation of aromatics over TS-I/H2O2 under solvent free triphase conditions. Catal Today, 49,185-191. 

Mason and coworkers [44,45] have for the first time observed that HRP catalyzes the hydroxylation of aromatic compounds by molecular oxygen in the pre-... 

The pattern of microbial hydroxylation of aromatic substrates appears to occur generally according to the usual rules of electrophilic aromatic substitution as shown by the hydroxylation positions of acronycine (1) at C-9 and C-11 (para- and ortho-positions to the amino group and mefa-position to the car-... 

An intramolecular hydrogen migration observed in the hydroxylation of aromatic rings in certain enzyme-catalyzed reactions as well as some chemical reactions. The rearrangement was first observed at the National Institutes of Health (hence the name NIH ) in studies of the synthesis of L-tyrosine from L-phenylalanine via phenylalanine hydroxylase. Observation of this shift requires appropriate deuteration of the aromatic reactant. 

The triflic acid catalyzed electrophilic hydroxylation of aromatics with BTSP gives the corresponding phenols in high yields without apparent polyhydroxylation or secondary oxidation. Thus, treatment of CeHe with CF3SO3H followed by BTSP gave 11% PhOH. The isomer distributions are in accord with the electrophilic nature of the reaction. The observed ortho/para ratio in the case of toluene agrees with the expected trends (Scheme 4 and Table ll) . 

TABLE 11. Hydroxylation of aromatics with BTSP/CE3SO3H... 

Co(ni) alkyl peroxides have been prepared and used by Mimoun and coworkers in the hydroxylation of hydrocarbons with this metal a Haber-Weiss type of reactivity is suggested. Square-planar Pt(II) complexes, of the type [(dppe)Pt(CF3)(solv)], used by Strukul in the epoxidation of alkenes and in Baeyer-Villiger oxidations of ketones (Schemes 8 and 9), are effective catalysts also in the direct hydroxylation of aromatics with hydrogen peroxide. The reactivity increases in the presence of electron releasing substituents in the aromatic ring. Ortho and para derivatives are practically the only products observed and interesting selectivity toward the ortho products has been detected (equation 85). 

Halfpenny, E., and Robinson, P. L. (1952a). The nitration and hydroxylation of aromatic compounds by pernitrous acid. J. Chem. Soc., 939-946. 

The aromatic amino add hydroxylases (AAHs) are a family of pterin-dependent enzymes comprising phenylalanine hydroxylase (PAH), tyrosine hydroxylase (TH), and tryptophan hydroxylase (TPH, with two gene products TPH1 and TPH2). The AAHs perform the hydroxylation of aromatic amino adds and play an important role in mammalian metabolism and in the biosynthesis of... 

The structural similarity of the catalytic domains of the enzymes of the AAH family, together with the identical reaction that they catalyze (i.e., hydroxylation of aromatic substrates) and the common dependency on BH4 and 02 (Section I), suggests that the mechanisms by which these enzymes operate are similar. It is assumed that the general AAH reaction mechanism follows a two-step reaction route in which a high-valent iron-oxo (FeIV=0) complex is formed in the first step, and that this intermediate is responsible for the hydroxylation of the aromatic amino acid substrate in the second step (15,26-28,50). The first step starts with 02 binding and activation and proceeds via a Fe-0-0-BH4 bridge and a subsequent heterolytic cleavage of the... 

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