Catechol, formation

Either the CO2 formation is followed potemiometrically (243) or the O2 consumption is measured amperometrically at an oxygen electrode (245). In the first method, the enzyme is physically immobilized with a dialysis membrane. The response is linear in the range 5-300 pg/mL of salicylate. The second technique uses chemically immobilized enzyme (GA -F BSA) attached to a pig intestine mounted on the tip of the O 2 electrode. Samples containing from 10 pM to 2 mM salicylate were analyzed. An elegant microelectrode (244) has the enzyme and the cofactor immobilized in the electrode matrix (carbon paste) and the catechol formation is monitored at -F 300 mV versus Ag/AgCl. The electrode consists of a disposable strip, allowing measurements to be made on a drop of blood within 1 min. 

RE Billings. Mechanisms of catechol formation from aromatic compounds in isolated rat hepatocytes. Drug Metab Dispos 13(3) 287—290, 1985. 

Modification of Y-AI2O3 by phosphoric acid was observed to lead to a significant increase in O/C alkylation ratio up to 7.33 from 2.45 for Y-AI2O3. The selectivity towards 4-methyl catechol formation is seen to be only slightly affected. The rise in surface basicity of Y-AI2O3 by incorporation of Mg " and Li cations into the lattice leads to the increase of 3-methyl catechol selectivity up to 0.65 at 7.5 at.% of Mg added. 

As is seen from Fig. 6, the increase in basicity leads to the important decrease in O-methylation rate (R2) without significant changing in the rate of 3-methyl catechol formation (R3) until 7.5 at.% of Mg ". At higher magnesium concentration the rate R3 goes down more rapidly, than for guaiacol formation. It results in the observed maximum for 3-methyl catechol selectivity at 7.5 at.% Mg V Y-AI2O3, reported as an optimal catalyst composition [4]. 

The reaction of catechol methylation in gas phase at temperatures below 300°C is seen to proceed efficiently over modified y-aluminas with moderate acid sites. At low catechol conversion (X < 0.05), O- and C-methylated products are formed in parallel reaction pathways. The 0/C methylation ratio has been regulated by varying acid/base properties of the catalyst. Modification of Y-AI2O3 by phosphoric acid was observed to increase the selectivity towards guaiacol formation (O-methylation) up to 82=0.89. The catalyst Mg (7.5 at.% )/ Y-AI2O3 showed the maximum selectivity towards 3-methyl catechol formation (C-methylation) to be 3=0.65. It means that a 20-fold change in the O/C methylation ratio was achieved, when the catalyst acidity was modified, keeping constant other reaction conditions. 

Higher amounts of zirconium (1.2 Zr/unit cell) could be incorporated in the MEL structure using Zr(IV) acetylacetonate as zirconium source without any precipitation during the gel preparation while ZrCU source could not be used beyond x > 0.01 as it yields material with low crystallinity (XRD), aggregated crystals (SEM) and non- homogenous gel during the synthesis. A higher catechol formation in Zr-Sil-2 (B) samples may be due to the surface acid sites. 

Table 15 summarizes the activity of various samples studied. On all catalysts, catechol (CAT) and hydroquinone (HQ) were formed as major products. Among the catalysts studied, CoNiAII5-HT showed maximum conversion of phenol (14,2%) with a CAT/HQ ratio of around 3.8. A closer look at the data indicated an increase in the conversion of phenol (with a preference of catechol formation) with an increase in concentration of nickel, up to a level and decreased with a further increase in the concentration. The most active catalyst (CoNiAl 15-HT) was taken for further study. 

With TS-1 as the catalyst, the oxidation products of phenol are hydro-quinone and catechol (para- and ort/to-hydroxyphenol), with minor yields of water and tar formed as by-products. Numerous early papers are concerned with this reaction (218), and patents (219) have been iiled. In the reaction catalyzed by TS-1, the conversion of phenol and the selectivity to dihydroxy products are significandy higher than achievable by either radical-initiated oxidation or acidic catalysts. The catechol/hydroquinone molar ratio is within the range of 0.5—1.3 and depends on the solvent. When the reaction occurs in aqueous acetone, the ratio is close to 1.3. It is believed that the product ratio is the result of restricted transition-state selectivity as well as mass transport shape selectivity associated with the different diffusivities of the ortho and para products. Hydroxylation at the para-position of phenol should be less hindered relative to that at the ortho-position, and hydroqui-none has a smaller kinetic diameter than catechol, facilitating diffusion. Tuel and Taarit (220) proposed that catechol is mainly produced at the external surface of TS-1 crystals. Thus, the different catechol/hydroquinone ratios obtained when methanol or acetone is used as a solvent could be explained by either rapid or very slow poisoning of external sites by organic deposits, respectively. Accordingly, the authors were able to show that tars were easily dissolved by acetone (i.e., external sites for catechol formation remained available in this solvent) while they were insoluble in methanol. 

Figure 1.9 Reaction pathway for phenoi hydroxyiation with H2O2 as the oxidizing agent and TS-1 as the catalyst. The relative rate constants characterizing product (hydroqui-none or catechol) formation and by-product (benzoquinone) formation and secondary reactions depend on the catalyst and are discussed in the text.

Notley et al. (2002) investigated the P450 forms responsible for covalent drug-protein adduct formation and the possibility that covalent adduct formation might occur via alternative pathways to catechol formation. Recombinant P450 3A4 catalysed... 

Phenol, anisole, and phenolic ethers are readily hydroxylated by hydrogen peroxide in the presence of microcrystalline ZrP and acetic acid (151). The selectivity for catechol formation was greater than 29% at 47% conversion, and hydroqui-... 

DFT and ab initio calculations have been used to study the mechanism of the gas-phase oxidation of phenol by HO. Addition of HO to the ort/io-position forms P2, which subsequently combines with O2 at the ip o-position to form adduct P2-1-00. A concerted HO2 elimination from P2-1-00 forms 2-hydroxy-3,5-cyclohexadienone (HCH) as the main product and is responsible for the rate constants for the reaction between P2 and O2 to be about two orders of magnitude higher than those between other aromatic-OH adducts and O2. The HCH subsequently isomerizes to catechol, which is thermodynamically more stable than HCH, possibly through a heterogeneous process. Reaction of P2 with NO2 proceeds by addition to form P2-n-N02 ( = 1, 3, 5) followed by HONO elimination from P2-1/3-N02 to form catechol. The barriers for HONO elimination and catechol formation are below the separate reactants P2 and NO2, being consistent with the experimental observation of catechol in the absence of O2, while H2O elimination from P2-I/3-NO2 forms 2-nitrophenol (2NP). The most likely pathway for 2NP is the reaction between phenoxy radical and N02." ... 

The formation of catechol from 2-nitrophenol (Fig. lA) and the conversion of 4-nitrophenol to 4-nitrocatechol (Fig. 1C) are examples of monooxygenase-catalysed catechol formation. Industrial applications of these types of reactions are the production of L-3,4-dihydroxyphenylalanine (L-DOPA) by hydroxylation of L-tyrosine by Vibrio tyrosi-naticus and several Pseudomonas species (46, 57, 64, 68, 69, Fig. 5A) and the conversion of 4-hydroxyphenylacetic acid to 3,4-dihydroxyphenylacetic acid by a flavin-dependent monooxygenase (1, 30, 39, 64, 67, Fig. 5B). Production of both catechols is of industrial interest because L-DOPA is an important drug for treatment of Parkinson s disease and 3,4-dihydroxyphenylacetic acid is a widely used precursor for the production of synthetic antibiotics. 

The main difference between the pathways depicted in Figure 7 is the involvement of the carboxyl function in the formation of the resonance-stabilized structures susceptible to further reaction. If the carboxyl function at the 1 -position is indeed important in the conversion of hydroxylaminoaromatic compounds to catechols, this might explain why catechol formation has only been found from 4-hydroxylaminobenzoate (20, 26, 51) and not from hydroxylami-nobenzene (41), 1-hydroxy-1-phenyl-3-methyl urea (62), 1-chloro-4-hydroxylaminobenzene (13) and hydroxylaminobiphenyls (7). These hydroxylaminoaromatic compounds, lacking a carboxyl function at the 1-position, were converted to the corresponding aminophenols. 

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