Aminophenols, formation

Biotransformation of acetaminophen by deace-tylase enzymes in liver or kidney produces the metabolite 4-aminophenol (Figure 4). Evidence suggests that acetaminophen nephrotoxicity may result from 4-aminophenol formation. In animal studies, 4-ami-nophenol is a more potent nephrotoxicant than acetaminophen and inhibition of deacetylase enzymes also attenuates acetaminophen nephrotoxicity. Deacetylase enzymes are also present in higher levels in renal cortex, the target for acetaminophen nephrotoxicity, than in liver or renal medulla and there is a positive correlation between renal cortex... 

Reduction to aminophenol. Reduce about 0 5 g. of o-nitrophenol with cone. HCl and tin as described on p. 385. After a few minutes the yellow molten o-nitrophenol disappears completely, the solution becoming homogeneous and colourless due to the formation of 0-aminophenol (which is soluble in HCl). Cool and add 30% aqueous NaOH solution note that a white precipitate is first formed and then redissolvcs in an excess of NaOH, and that the solution does not develop an orange coloration, indicating that the nitro-group has been reduced. 

The aminophenols are chemically reactive, undergoing reactions involving both the aromatic amino group and the phenoHc hydroxyl moiety, as weU as substitution on the benzene ring. Oxidation leads to the formation of highly colored polymeric quinoid stmctures. 2-Aminophenol undergoes a variety of cyclization reactions. 

The formation of enamines from carbonyl compounds and secondary amines usually entails as only questionable structural feature, the possible isomeric position of double bonds in the product. Molecular rearrangements have not presented synthetic limitations. A notable exception is the generation of o-aminophenols on distillation of enamines derived from 2-acylfurans 620,621). 

I-A1ON0-2-NAPHIH0L-4-SULE0NIC acid, 11, 72 16, 91 17, 91 Aminonaphtholsulfonic acids, coupling to form azo dyes, 16,16 p-Aminophenol, 16, 39 Aminopiperole, 16, 6 /3-Ahinopropionic acid, 16, 1 4-Aminoveratrole, 16, 4 Ammonium dichromate, 16, 74 Ammonium formate, 17, 77 Ammonium thiocyanate, 16, 74 Ammonium vanadate, 13, 1 to w-Amyl alcohol, IS, 17 hri.-Amyl alcohol, 13, 68 -Amylbenzene, 10, 4 -Amyl borate, 13, 17 -Amyl bromide, 16, 41 iso-Amyl iodide, 13, 62 n-Amyl iodide, 13, 62 n-Amybnagnesium bromide, 16, 41... 

Snznki H, Y Fnrnsho, T Higashi, Y Ohnishi, S Horinonchi (2006a) A novel o-aminophenol oxidase responsible for formation of the phenoxazinone chromophore of grixazone. J Biol Chem 281 824-833. 

Aminophenol was being oxidised in THF solution at 65°C using a larger than normal proportion of potassium dioxide. When stirring was stopped after 6 h, a violent explosion occurred. This was attributed to formation of tetrahydrofuranyl hydroperoxide by the excess dioxide. THF was described as an unsafe solvent for superoxide reactions [1], A later attempt at the same reaction in toluene also led to explosion, now blamed on the substrate [2],... 

An interesting observation was made when o-aminophenol (2-411) was employed in the reaction with carbethoxypiperidone 2-410 and acrolein (Scheme 2.98). In this case, the spirocydic scaffold 2-412 was exclusively formed in 67% yield. This result can be explained by invoking a stereoelectronic control due to the presence of the aromatic ring which prevents the formation of the corresponding fused tetracyclic isomer. Moreover, both reactive sites can simultaneously be functionalized using 2-amino-1,3-propanediol (2-413) as partner in the multicomponent reaction. This leads to the formation of three new cycles... 

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). 

One of numerous examples of LOX-catalyzed cooxidation reactions is the oxidation and demethylation of amino derivatives of aromatic compounds. Oxidation of such compounds as 4-aminobiphenyl, a component of tobacco smoke, phenothiazine tranquillizers, and others is supposed to be the origin of their damaging effects including reproductive toxicity. Thus, LOX-catalyzed cooxidation of phenothiazine derivatives with hydrogen peroxide resulted in the formation of cation radicals [40]. Soybean LOX and human term placenta LOX catalyzed the free radical-mediated cooxidation of 4-aminobiphenyl to toxic intermediates [41]. It has been suggested that demethylation of aminopyrine by soybean LOX is mediated by the cation radicals and neutral radicals [42]. Similarly, soybean and human term placenta LOXs catalyzed N-demethylation of phenothiazines [43] and derivatives of A,A-dimethylaniline [44] and the formation of glutathione conjugate from ethacrynic acid and p-aminophenol [45,46],... 

Acetal formation, microwaves in, 76 557 Acetalization, of PVA, 25 602-603 Acetal polymerization, 74 271 Acetal resins, 70 183-185 Acetal resins, formaldehyde in, 72 122 Acetals, 2 64 70 529 aroma chemicals, 3 253 inorganic pigment applications, 7 372t organic pigment applications, 7 368t typical soluble dye applications, 7 376t Acetaminophen, 4 701. See also AT-Acetyl-p-aminophenol (acetaminophen)... 

The spirophosphorane (74) has been identified as an intermediate in the formation of (75) from o-aminophenol and trisdiethylaminophosphine.61 With ethylene glycol (75) gave high yields of the phosphoranes (76) and (77). As expected, the phosphoranes (78) have apical fluorine atoms.52 The interesting bicyclic phosphoranes (79) and (80) have been prepared as shown.63... 

N3P3C16 to phosphoranes by or/Ao-dinucleophiles such as o-aminophenol and catechol.130 Thus it has now been shown that the intermediate (58), in the formation of (59), can be isolated from reactions with the former dinucleophile, but (58) is more conveniently isolated from the reaction of non-geminal N3P3Cl3(NMe2)3 with o-aminophenol. 

Upon reaction of 4-nitrosobiphenyl with thiols, its negative Hammett constant (op+ = —0.1855) is expected to facilitate formation of a sulfenamide cation that may delocalize its positive charge partly to C(3), C(2q and C(4/). Hence formation of aminophenols and acid-stable hemoglobin adducts would be conceivable. 

Corey s retrosynthetic concept (Scheme 9) is based on two key transformations a cationic cyclization and an intramolecular Diels-Alder (IMDA) reaction. Thus, cationic cychzation of diene 50 would give a precursor 49 for epf-pseudo-pteroxazole (48), which could be converted into 49 via nitration and oxazole formation. Compound 50 would be obtained by deamination of compound 51 and subsequent Wittig chain elongation. A stereocontroUed IMDA reaction of quinone imide 52 would dehver the decaline core of 51. IMDA precursor 52 should be accessible by amide couphng of diene acid 54 and aminophenol 53 followed by oxidative generation of the quinone imide 52 [28]. 

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