Catechol, reactions derivatives

The mechanistic studies of a chiral Brpnsted acid-catalysed asymmetric reduction of ketones with catecholborane as the reducing agent to give highly enantioselective chiral secondary alcohols indicated that phosphoryl catechol borate, derived from reaction of the Brpnsted acid with catecholborane, acts as the active catalyst. ... 

Catechol Derivatives. An elegant synthesis of trimethoxybenzaldehyde [86-81-7] (4) starting from quaiacol [90-05-1] (5) and formaldehyde (75) has been developed. The reaction sequence is as follows ... 

Conversion of Aromatic Rings to Nonaromatic Cyclic Structures. On treatment with oxidants such as chlorine, hypochlorite anion, chlorine dioxide, oxygen, hydrogen peroxide, and peroxy acids, the aromatic nuclei in lignin typically ate converted to o- and -quinoid stmctures and oxinane derivatives of quinols. Because of thein relatively high reactivity, these stmctures often appear as transient intermediates rather than as end products. Further reactions of the intermediates lead to the formation of catechol, hydroquinone, and mono- and dicarboxyhc acids. 

The main product of the Elbs reaction is the 1,4-dihydroxybenzene (hydro-quinone). If the para position is already occupied by a substituent, the reaction occurs at an ortho position, leading to a catechol derivative although the yields are not as good as for a hydroquinone. Better yields of catechols 7 can be obtained by a copper-catalyzed oxidation of phenols with molecular oxygen ... 

In some cases enzymes can increase the rate of reaction by up to lO times. Carnell and Roberts (1997) have briefly discussed the scope of biotransformations that are used to make pharmaceuticals like penicillins, cephalosporines, erythromycin, lovastatin, cyclosporin, etc., and for food additives like citric acid, L-glutamate, and L-lysine. A very successful transformation by Zeneca has been that of benzene reduction, with Pseudomonase Putida, to dihydrocatechol and catechol the dihydro derivative is used to produce (+/-) pinitol. Fluorobenzene has been converted to fluorodihydrocatechol, an intermediate for pharmaceuticals. The highly stereo selective Bayer-Villeger reaction has been carried out with genetically engineered S-cerevisvae. Hydrolases have allowed enantioselective, and in some cases regioselective, hydrolysis of racemic esters. 

As depicted in the following scheme, in the presence of sodium iodate and pyridine, several 5,6-dihydroxylated benzofuran derivatives were synthesized via an oxidation-Michael addition of P-dicarbonyl compounds to catechols in a one-pot procedure <06TL2615 06JHC1673>. A novel additive Pummerer reaction of 2-benzo[fc]furan sulfilimines with carbon nucleophiles derived from P-dicarbonyl compounds was also employed to the synthesis of 2,3-disubstituted benzo[b]furans <06TL595>. 

Various hydroxyl and amino derivatives of aromatic compounds are oxidized by peroxidases in the presence of hydrogen peroxide, yielding neutral or cation free radicals. Thus the phenacetin metabolites p-phenetidine (4-ethoxyaniline) and acetaminophen (TV-acetyl-p-aminophenol) were oxidized by LPO or HRP into the 4-ethoxyaniline cation radical and neutral V-acetyl-4-aminophenoxyl radical, respectively [198,199]. In both cases free radicals were detected by using fast-flow ESR spectroscopy. Catechols, Dopa methyl ester (dihydrox-yphenylalanine methyl ester), and 6-hydroxy-Dopa (trihydroxyphenylalanine) were oxidized by LPO mainly to o-semiquinone free radicals [200]. Another catechol derivative adrenaline (epinephrine) was oxidized into adrenochrome in the reaction catalyzed by HRP [201], This reaction can proceed in the absence of hydrogen peroxide and accompanied by oxygen consumption. It was proposed that the oxidation of adrenaline was mediated by superoxide. HRP and LPO catalyzed the oxidation of Trolox C (an analog of a-tocopherol) into phenoxyl radical [202]. The formation of phenoxyl radicals was monitored by ESR spectroscopy, and the rate constants for the reaction of Compounds II with Trolox C were determined (Table 22.1). 

This intramolecular etherification approach has successfully been applied to the syntheses136 of siccanin137 and clusifoliol,136 and a formal synthesis of morphine.138 Examples of tandem inter- and intramolecular etherification reactions have also been reported which convert catechol and o-aminophenol derivatives into benzodioxins (Equation (24)),139-141 benzodioxepines,142 and morpholines.139,140... 

Plasma levels of dobutamine hydrochloride are determined by reaction of the drug with 3H-methyl-S-adenosylmethionine in the presence of catechol O-methy1-transferase. The radioactivity of the labeled methyl derivative is determined by a liquid scintillation counter using an external standard. The final recovery of added dobutamine as 3H-CH3-dobutamine is 24.9 1.3% in the range of 2 to 170 ng/ml (4). When 14C-dobutamine is administered the samples are counted by a double isotope method. 

Palladium-catalyzed reactions of arylboronic acids have been utilized to craft precursors for constructing indole rings. Suzuki found that tris(2-ethoxyethenyl)borane (149) and catechol-derived boranes 150 readily couple with o-iodoanilines to yield 151, which easily cyclize to indoles 152 with acid [158]. Kumar and co-workers used this method to prepare 5-(4-pyridinyl)-7-azaindoles from 6-amino-5-iodo-2-methyl-3,4 -bipyridyl [159], A similar scheme with catechol-vinyl sulfide boranes also leads to indoles [160]. A Suzuki protocol has been employed by Sun and co-workers to synthesize a series of 6-aryloxindoles [161]. 

It was found that catechol derivatives in general were able to protect cholinesterases in vitro. Both horse-serum and rat-brain cholinesterases were protected against the above inhibitors. It is thought that the basis of the protection is a reaction between catechol and the inhibitor. 

Cycloaddition Reactions with Other Nucleophiles The anodic two-electron oxidation of catechol affords o-quinone that may react with the enolates of 4-hydroxycoumarine or 5,5-dimethyl-1,3-cyclohexanedione (dimedone). The resulting adducts undergo a second anodic oxidation leading to benzofuran derivatives in good yields (90-95%) (Scheme 53) [75, 76]. 

BDNF, brain-derived neurotrophic factor DAT, dopamine transporter DRD, dopamine receptor MAOA, monoamine oxidase A MB-catechol-O-methyltransferase QM-MSP, quantitative multiplex methylation-specific polymerase chain reaction RELN, reelin TH. These primers are suitable for QM-MSP. 

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