P-Quinone imine

In another study, Si et al. reported recently that PEDOT-GO could be used for the electrochemical detection of AP [95]. The detection is based on oxidation of AP to N-acetyl-p-quinone-imine. The PEDOT-GO film was S5mthesized at a constant potential of 1.2 V for 24 s from an aqueous solution containing EDOT and GO as the only counterion. It was found that the GO sheets were covered with PEDOT nanodots. The relatively rough PEDOT-GO layer was different from the uniform PEDOT-GO layer reported by the same authors in ref [94] and it was expected to be beneficial for the AP detection. 

Oxidation H ir Colorant. Color-forming reactions are accompHshed by primary intermediates, secondary intermediates, and oxidants. Primary intermediates include the so-called para dyes, -phenylenediamine, -toluenediamine, -aminodiphenylamine, and p- am in oph en o1, which form a quinone monoimine or diimine upon oxidation. The secondary intermediates, also known as couplers or modifiers, couple with the quinone imines to produce dyes. Secondary intermediates include y -diamines, y -aminophenols, polyhydroxyphenols, and naphthols. Some of the more important oxidation dye colors are given in Figure 1. An extensive listing is available (24,28). 

Scheme 20 Anodic conversion of p-methoxyanilide to quinone imine.

One example of the effect of substitution on biological potency involves the popular drug acetaminophen (Tylenol ). Acetaminophen is almost completely metabolized in the liver with the production of harmless products that are excreted through the kidneys. A small amount of the drug maybe metabolized, however, to a toxic product, N-acetyl-p-henzo-quinone imine. In cases where large quantities... 

Researchers have found that the substitution of two methyl groups on the benzene ring in the acetaminophen molecule results in the formation of an analog that is essentially resistant to the metabolic reactions that result in the formation of N-acetyl-p-henzo-quinone imine and, hence, prevent toxic reactions involved with the use of acetaminophen. Researchers believe that the presence of the methyl groups interferes with enzyme actions that, in the first step of the reaction by which N-acetyl-p-benzo-quinone imine is produced, convert hydrogen atoms on the benzene rings in acetaminophen to hydroxyl groups. 

N itro phenyl inline) Udiozonium l,4 benzo quinone[called 2-Nitrophenyl-p-phenylenediazo-imine by Morgan MicklethwaitfRef 2) and p -Chinon-(2-nitro-anil)-diazid or 2 -Nitro-4-diazo... 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C=N bonds has recently been studied by the authors group.84 Treatment of 2-(diazoace-tyl)benzaldehyde O-methyl oxime (176) with rhodium(II) octanoate in the presence of dimethyl acetylenedicarboxylate or N-phenylmaleimide produced cycloadducts 178 and 179, respectively. The cycloaddition was also carried out using p-quinone as the dipolarophile. The major product isolated corresponded to cycloadduct 180. The subsequent reaction of this material with excess acetic anhydride in pyridine afforded diacetate 181 in 67% overall yield from 176. The latter compound incorporates the basic dibenzofa, d -cyclohepten-5,10-imine skeleton found in MK-801,85 which is a selective ligand for brain cyclidine (PCP) receptors that has attracted considerable attention as a potent anticonvulsive and neuro-protective agent.86,87... 

Many xenobiotics, including a wide variety of quinones and nitro compounds, will accept an electron from almost any redox flavoenzyme. The microsomal reduction of nitroaromatic compounds, quinones, quinone-imines, some azoaromatic compounds, paraquat, and tetrazolium salts is catalyzed by NADPH-cytochrome P-450 reductase [44], One-electron transfer to these electron acceptors has been proved to be obligatory in the case of quinone and nitro compounds, and is probably obligatory in other cases as well. Therefore, a reduction of an aromatic compound by NADPH-cytochrome P-450 reductase can probably be assumed to form a free radical metabolite. In contrast, free radical formation by reductive dehalogenation is totally cytochrome P-450-dependent, with the reductase being inactive. 

Oxidative demethylation A new approach to indoloquinones such as 5 involves Michael addition of ethyl acetoacetate to the quinone monoimide 1 to give 2, which is dehydrated to the indole 3 in 73% overall yield. The latent quinone ring is then modified to give the p-methoxyaniline 4. The final step involves the oxidative demethylation reaction of Rapoport (4, 431-432) to give an intermediate quinone imine, which is hydrolyzed to 5. 

Quinone imine ketals have also been recognized to be quite useful for heterocycle synthesis. In a series of quinone mono- and bis-ketal chemistry, Swenton and coworkers carried out anodic oxidation of trifluoroacetamido-substituted p-methoxyphenols . For example, the readily available p-methoxyphenol derivative 88 underwent constant current electrolysis (60 mA) in 2% LiC104 in methanol, followed by hydrolysis with 5% aqueous KOH to afford quinone imine ketal 89 in 82% overall yield, through quinone monoketal 90 (Scheme 17). Furthermore, acid treatment of 89 with TsOH provided 5-methoxyindole (91). 

A series of p-aryloxy- and p-alkoxyphenylnitrenium ions have been generated in aqueous solutions by photolysis of the parent azides, whereupon the resulting nitrenes are protonated. Hydration of these cations at the para position leads via hemiacetal or halohydrin intermediates to quinone imines, which finally hydrolyse to the ultimate quinone products. In flash-photolysis studies of these reactions it was shown that nitrenium ion hydration occurs on the ps timescale, hemiacetal or halohydrin breakdown on the MS timescale, and the final imine hydrolysis over minutes. 

Aromatic and aliphatic acyl isocyanates participate in a similar range of [4 + 2] cycloadditions although [2 + 2] and simple addition reactions often are observed. The acyl isocyanate substituents may determine or alter the observed course of the reaction, and the substituent effects have been detailed in extensive reviews.7,71 Observed [4 + 2] cycloadditions of acyl isocyanates with selected olefins, p-quinones, allenes, the carbon-carbon double bond of ketenes, electron-rich acetylenes, imines, dianils, ethy-lenediimines, enamines, enol ethers, ketene acetals, carbodiimides, azirines, and vinyl sulfides have been described.7 0 The reaction of aromatic acyl isocyanates with carbodiimides is not a simple, direct [4 + 2] cycloaddition but proceeds by a kinetic [2 + 2] cycloaddition followed by a subsequent rearrangement to provide the observed [4 + 2] cycloadduct [Eq. (40)].97... 

In further studies relevant to the mechanism of the Mitsunobu reaction, the reaction of diphenylphosphine (40) with di-isopropyl azodicarboxylate (41) was found to give a mixture of products one of which was assigned structure (44) formed via (42) and (43). The reaction of trico-ordinate phosphorus compounds with ortho-quinones,p-ketoalkenes and p-ketoimines is also a well-established source of pentaco-ordinate phosphorus compounds but in some cases the dipolar ion structure is more stable. Thus the reaction of (4Sab) with (46) produced the dipolar ion structures (47ab) but on the other hand, reaction of (45b) with the quinone imine (48) produced what appeared to be an equilibrium mixture of (49) and the pentaco-ordinate structure (50). The 1,3,2-X o -diazaphospholenes (Slab) have proved to be useful synthetic reagents in that on hydrolysis they yield the bis-hydroxylamine (52) which reacts with benzaldehyde to form the imidazoline (53). ... 

Nicotera P, Rundgren M, Porubek DJ, Cotgreave I, Moldeus P, Orrenius S, Nelson SD (1989) On the role of Ca2+ in the toxicity of alkylating and oxidizing quinone imines in isolated hepatocytes. Chem Res Toxicol 2 46-50... 

Trifluoromethyl-indoles can be prepared in a similar manner as shown in Eq. 64. In this case, anodic oxidation provides p-benzo-quinone imine derivatives 29, which are easily converted into trifluoromethyl-indoles 30 by heating or by treatment with ceric ammonium nitrate. 

However, in a pharmacokinetic study in 10 healthy subjects of both slow and fast acetylator status, isoniazid 300 mg daily for 7 days modestly decreased the total clearance of a single 500-mg dose of paracetamol by 15%. Moreover, the clearance of paracetamol to oxidative metabolites was decreased Similarly, in a further study in 10 healthy slow acetylators of isoniazid, the formation of paracetamol thioether metabolites and oxidative metabolites was reduced by 63% and 49%, respectively, by isoniazid 300 mg daily. However, one day after stopping isoniazid, the formation of thioether metabolites was increased by 56%, and this returned to pretreatment values 3 days after the discontinuation of isoniazid. In yet another study in 10 healthy subjects taking isoniazid prophylaxis, the formation clearance of paracetamol to A -acetyl-p-benzo-quinone imine (NAPQI) was inhibited by 56% when the paracetamol was given simultaneously with the daily isoniazid dose, but when the paracetamol was taken 12 hours after the isoniazid, there was no difference in NAPQI formation clearance, compared with the control phase (1 to 2 weeks after isoniazid had been discontinued). However, when the results were analysed by acetylator status, it appeared that the NAPQI formation clearance was increased in fast acetylators taking paracetamol 12 hours after the isoniazid dose. ... 

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