P-Aminophenol derivatives

The above method of sulfonation with sulfurous acid finds further application in the preparation of p-aminophenoldisulfonic acad from nitrosodimethylaniline and sodium bisulfite. In the rearrangement to the disulfom c acad, the dimethylamino group is split off with the formation of the p-aminophenol derivative. Pure dimethyl-amine is formed in the reaction. 

The structure-activity relationships of p-aminophenol derivatives have been widely studied. Based on the comparative toxicity of acetanilide and acetaminophen, aminophenols are less toxic than the corresponding aniline derivatives, although p-aminophenol itself is too toxic for therapeutic purposes. Etherification of the phenolic function with methyl or propyl groups produces derivatives with greater side effects than with ethyl groups. Substituents on the nitrogen atom that reduce basicity reduce activity unless that substituent is metabolically labile (e.g., acetyl). Amides derived from aromatic acids (e.g., N-phenylbenzamide) are less active or inactive. 

Analgesics, Antipyretics and Antirheumatic Agents a) p-Aminophenol Derivatives, Pyrazolones etc. 

The position is more complex with derivatives of o- and p-aminophenol. The three reduction waves of o-aminophenol derivatives were attributed to one-electron reduction of quinoid (first wave) and benzenoid (second wave) tautomeric forms of these compounds and to subsequent one-electron reaction of intermediate radical anions (third, total wave). With the p-aminophenol derivatives, reduction of which results in the appearance of two waves on the polarograms, it was assumed that the first wave of the benzenoid form merges with the wave for subsequent reduction of both tautomers. Unfortunately the authors cite no evidence for this tautomer-ism from other methods. In the case of the o-derivatives the intramolecular hydrogen bond could stabilize the benzenoid structure. 

Suspend 11 g. of p-aminophenol in 30 ml. of water contained in a 250 ml. beaker or conical flask and add 12 ml. of acetic anhydride. Stir (or shake) the mixture vigorously and warm on a water bath. The solid dissolves. After 10 minutes, cool, filter the solid acetyl derivative at the pump and wash with a little cold water. Recrystallise from hot water (about 75 ml.) and dry upon filter paper in the air. The yield of p-acetylaminophenol, m.p. 169° (1), is 14 g. 

HPLC method with amperometric detection was applied for detenuination of phenols in sea sediment and some dmg preparation. Peaks of phenol, guaiacol, cresols, hydroquinon and resorcinol were identified on chromatogram of birch tai. The HPLC method with electrochemical detectors was used for detenuination of some drug prepai ation of aminophenol derivate. So p-acetaminophenol (paracetamol) was determined in some drug. 

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],... 

Quinone is produced in small yield by direct oxidation of benzene itself with silver peroxide, but better by the action of oxidising agents on a large number of its p-disubstitution products. Thus, in addition to quinol, p-aminophenol (experiment, p. 176), p-anisidine, p-toluidine, and sulphanilic acid as well as p-phenylenediamine and many of its derivatives yield quinone in this way. 

The figure represents the chemical structure for paracetamol, which includes the N-(4-hydroxyphenyl) acetamide, derived from the interaction of p-aminophenol and an aqueous solution of acetic anhydride. The structure has two activating groups that make the benzene ring highly reactive toward electrophilic aromatic substitution. 

Epichlorohydrin is reacted with a variety of hydroxy, carboxy, and amino compounds to form monomers with two or more epoxide groups, and these monomers are then used in the reaction with bisphenol A [Lohse, 1987]. Examples are the diglycidyl derivative of cyclohex-ane-l,2-dicarboxylic acid, the triglycidyl derivatives of p-aminophenol and cyanuric acid, and the polyglycidyl derivative of phenolic prepolymers. Epoxidized diolefins are also employed (Sec. 9-8). 

HO.C H,.N2) Cr207 N 12.2%, crysts, mp- expl ca 154° when dry and pure was prepd by diazo-tization of p-aminophenol followed by addn of a dichromate. It is fairly stable, but less so than the chromate obtd from p-phenylenediamine(Ref 2,pp 4-5). The same author prepd chromates of diazonium and nitrodiazonium derivatives of aniline, bromoaniline, chloroaniline, benzidine, p-phenylenediamine, etc and found them more or less expl when dry... 

Examples of the preparation of alkyl benzyl ethers by the Williamson synthesis are included in Section 5.6.2, p. 583. An example of an alkyl phenyl ether is provided by the synthesis of phenacetin (Expt 6.109) where p-aminophenol is first converted into its Af-acetyl derivative by reaction with slightly more than one equivalent of acetic anhydride. Treatment of the product with ethanolic sodium ethoxide solution followed by ethyl iodide then yields the ethyl ether of AT-acetyl-p-phenetidine (phenacetin). This compound is biologically active and has been widely employed for example as an antipyretic and analgesic however, owing to undesirable side reactions, its use is now restricted. 

Hydroxydiazonium salts derived from o- and p-aminophenols change... 

The action of nitric acid on diacetylated p-aminophenol yields a dinitro derivative for which four structures are possible. Hydrolysis followed by deamination gives the known 3,5-dinitrophenol, thus proving that substitution occurs ortho to the acylated amino group.141... 

Both phenacetin and the newer replacement acetaminophen are derivatives of p-aminophenol. Although these latter two are analgesics and antipyretics, the aniline-phenol derivatives show little if any antiinflammatory activity. p-Aminophenol itself is toxic, but acylation of the amino group makes it a convenient drug. 

Sainthorant C, Morin P, Dreux M, Baudry A, Goetz N. Separation of phenylenedia-mine, phenol and aminophenol derivatives by micellar electrokinetic chromatography. comparison of the role of anionic and cationic surfactants. J Chromatogr A 1995 717 167. 

N-(t-ButylMo)-p-benzoquinonimines. These derivatives of quinonimincs are obtained by reaction of p-aminophenols with 1 in CH3CN. Addition of CuCU generally improves the yield (6-45%). ... 

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