Direct Hydroxylation of Aromatic Compounds

Sato, K., Hanaoka, T., Niwa, S., et al. (2005). Direct Hydroxylation of Aromatic Compounds by a Palladium Membrane Reactor, Catal. Today, 104, pp. 260-266. 

The application of direct electrochemistry of small redox proteins is not restricted to cytochrome c. For example, the hydroxylation of aromatic compounds was possible by promoted electron transfer from p-cresol methylhydroxylase (a monooxygenase from Pseudomonas putida) to a modified gold electrode [87] via the blue copper protein azurin. All these results prove that well-oriented non-covalent binding of redox proteins on appropriate electrode surfaces increases the probability of fast electron transfer, a prerequisite for unmediated biosensors. Although direct electron-transfer reactions based on small redox proteins and modified electrode surfaces are not extensively used in amperometric biosensors, the understanding of possible electron-transfer mechanisms is important for systems with proteins bearing catalytic activity. 

There are two directions in the development of supramolecular catalytic compositions, that is, (1) creation of systans based on macrocyclic compounds as host molecules that bind substrates with their hydrophobic cavity and (2) development of the systems that bind substrates using aggregates formed by am-phiphihc compounds. Compounds that form host-guest complexes like modified cahxarenes are able to aid transport of substrates into the aqueous phase. This approach has been implemented in the Wacker oxidation [40,41], oxidation of alkylaromatic compounds [42], hydroxylation of aromatic compounds [43], hydrogenation [44,45], hydroformylation [45-48], and carbonylation [49]. In this case, the substrate is transported into the aqueous phase in the form of the corresponding inclusion complex. This not only affects the activity of the catalyst, but also provides selectivity of the process. Thus, in the Wacker oxidation of 1-alkenes the maximum yield of methyl ketone was achieved when 1-hexene is used, and for systems based on calix[6]arene with 1-octene among catalytic systems with modified calix[4]arenes [50]. 

Catechols are important intermediates in agrochemical, pharmaceutical, petrochemical and flavor industries. However, organic chemical synthesis of these compounds by direct hydroxylation of the aromatic ring is difficult, as the reaction products are usually not stable under the reaction conditions employed (24,36,44). Biotechnological production processes for catechols are, therefore, of great interest. As outlined below, several processes based on the direct biological oxidation of aromatic structures have been studied. 

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. 

Nishioka MG, CC Howard, DA Conros, LM Ball (1988) Detection of hydroxylated nitro aromatic and hydroxy-lated nitro polycyclic aromatic compounds in ambient air particulate extract using bioassay-directed fractionation. Environ Sci Technol 22 908-915. 

Direct spectrophotometric methods have been proposed for both particulate and dissolved lignosulfonic materials. Kloster [436] used the Folin Ciocal-teumethod, which actually measures hydroxylated aromatic compounds. A general review of spectrophotometric methods was published by Bilikova [437]. 

The biotransformation of clofexamide (4.33, Fig. 4.4), a compound with anti-inflammatory and antidepressant activities, was investigated in rats [18]. About 15% of the dose administered was found in urine as 2-(4-chlorophe-noxy)acetic acid (4.37). This metabolite was formed via the secondary amine 4.34, the primary amine 4.35, and the acid 4.36 resulting from oxidative deamination. However, direct formation of 2-(4-chlorophenoxy)acetic acid (4.37) from the parent compound (4.33) cannot be excluded. Clofexamide and its metabolite 4.34 also underwent hydroxylation on the aromatic ring, but these hydroxylated metabolites did not appear to be hydrolyzed. 

Nishioka, M. G., C. C. Howard, D. A. Contos, L. M. Ball, and J. Lewtas, Detection of Hydroxylated Nitro Aromatic and Hy-droxylated Nitro Polycyclic Aromatic Compounds in an Ambient Air Particulate Extract Using Bioassay-Directed Fractionation, Environ. Sci. Technol., 22, 908-915 (1988). 

Phenylpropanes are aromatic compounds with a propyl side chain attached to the benzene ring, which can be derived directly from phenylalanine. Naturally occurring phenylpropanoids often contain oxygenated substituents, e.g. OH, OMe or methylenedioxy, on the benzene ring. Phenylpropanoids with hydroxyl substituent(s) on the benzene ring belongs to the group of phenolics, e.g. caffeic acid and coumaric acid. 

The nature of the substituent in a substituted aromatic compound influences the position of hydroxylation. Thus, o-p-directing substituents, such as amino groups, result in o-and... 

What are phenolic compounds They are compounds that have one or more hydroxyl groups attached directly to an aromatic ring. Phenol (1.1) is the structure upon which the entire group is based. The aromatic ring in this case is, of course, benzene. 

The excited states of substrate species are very reactive. They react with available free-radical oxidants with subsequent generation of partially oxidized intermediates. Although organic compounds are assumed to react predominantly with HO and H02 /02 y degradation of certain compounds can also take place directly by activation caused by UV, which improves the ability of the organics to be oxidized by H2Oz or hydroxyl radicals. Certain aromatics and olefins can also react with H202 directly. Phenol is an extensively studied example. These reactions may further enhance the oxidation of aromatics and olefins. The reaction intermediates (Int) are unstable and are further oxidized to mineral species (C02, HzO, and HC1) ... 

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