Aminophenols quinones

Add 4 4 g. of recrystaUised -phenylhydroxylamine to a mixture of 20 ml. of concentrated sulphuric acid and 60 g. of ice contained in a 1 litre beaker cooled in a freezing mixture. Dilute the solution with 400 ml. of water, and boil until a sample, tested with dichromate solution, gives the smell of quinone and not of nitrosobenzene or nitrobenzene (ca. 10-15 minutes). Neutralise the cold reaction mixture with sodium bicarbonate, saturate with salt, extract twice with ether, and dry the ethereal extract with anhydrous magnesium or sodium sulphate. Distil off the ether p-aminophenol, m.p. 186°, remains. The yield is 4-3 g. 

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). 

It was previously mentioned in Section 1.2 that the products of diazotizing o- and /7-aminophenols exist in neutral aqueous solutions as zwitterions (1.7 b) which are mesomeric with the corresponding quinone diazides (1.7 a). They can therefore be... 

The major problem of these diazotizations is oxidation of the initial aminophenols by nitrous acid to the corresponding quinones. Easily oxidized amines, in particular aminonaphthols, are therefore commonly diazotized in a weakly acidic medium (pH 3, so-called neutral diazotization) or in the presence of zinc or copper salts. This process, which is due to Sandmeyer, is important in the manufacture of diazo components for metal complex dyes, in particular those derived from l-amino-2-naphthol-4-sulfonic acid. Kozlov and Volodarskii (1969) measured the rates of diazotization of l-amino-2-naphthol-4-sulfonic acid in the presence of one equivalent of 13 different sulfates, chlorides, and nitrates of di- and trivalent metal ions (Cu2+, Sn2+, Zn2+, Mg2+, Fe2 +, Fe3+, Al3+, etc.). The rates are first-order with respect to the added salts. The highest rate is that in the presence of Cu2+. The anions also have a catalytic effect (CuCl2 > Cu(N03)2 > CuS04). The mechanistic basis of this metal ion catalysis is not yet clear. 

For many decades intramolecular O-coupling was considered not to take place in the diazotization products of 2-aminophenol and its derivatives (for a contrary opinion see, however, Kazitsyna and Klyueva, 1972). The compounds were assumed to be present as one structure only, which can be represented as a mesomer of a phenoxide diazonium zwitterion 6.63 b and a diazocyclohexadienone 6.63 a (see reviews by Kazitsyna et al., 1966 Meier and Zeller, 1977 Ershov et al., 1981). In IUPAC nomenclature 6.63 is called 1,2-quinone diazide, in Chemical Abstracts 6-diazo-2,4-cyclohexadien-one (see Sec. 1.3). More recently, however, Schulz and Schweig (1979, 1984) were able to identify the intramolecular product of O-coupling, i.e., 1,2,3-benzooxadiazole (6.64) after condensation of 6.63 in vacuo at 15 K in the presence of argon (see Sec. 4.2). 

Polypyrrole shows catalytic activity for the oxidation of ascorbic acid,221,222 catechols,221 and the quinone-hydroquinone couple 223 Polyaniline is active for the quinone-hydroquinone and Fe3+/Fe2+ couples,224,225 oxidation of hydrazine226 and formic acid,227 and reduction of nitric acid228 Poly(p-phenylene) is active for the oxidation of reduced nicotinamide adenine dinucleotide (NADH), catechol, ascorbic acid, acetaminophen, and p-aminophenol.229 Poly(3-methylthiophene) catalyzes the electrochemistry of a large number of neurotransmitters.230... 

Polyhydroxybenzenes or aminophenol derivatives can be considered as leuco quinones or leuco quinoneimines. They are easily oxidized and couple... 

Antioxidants that break chains by reactions with peroxyl radicals. These are reductive compounds with relatively weak O—H and N—H bonds (phenols, naphthols, hydro-quinones, aromatic amines, aminophenols, diamines), which readily react with peroxyl radicals forming intermediate radicals of low activity. 

In the experiment described above, the p-aminophenol is not isolated but converted by oxidation into quinone. 

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 major problem of these diazotizations is oxidation of the initial aminophenols by nitrous acid to the corresponding quinones. Easily oxidized amines, in particular aminonaphthols, are therefore commonly diazotized in a weakly acidic medium (pH 3) so-called neutral diazotization or in the presence of zinc or copper salts. This process, which is due to Sandmeyer, is important in the manufacture of diazo components for metal complex dyes, in particular those derived from l-amino-2-naphthol-4-sulfonic acid. 

Cram and Day 57> successfully synthesized a quinone of [2.2]para-cyclophane by coupling the phenol 148 with diazotized sulphanilic acid to give 149. Reduction of 149 gave the unstable aminophenol 150 on oxidation with ferric sulphate 150 afforded the quinone 30 in 68% overall yield. 

Covalent protein adducts of quinones are formed through Mchael-type addihon reachon with protein sulfhydryl groups or glutathione. Metabolic activahon of several toxins (e.g., naphthalene, pentachlorophenol, and benzene) into quinones has been shown to result in protein quinone adducts (Lin et al, 1997 Rappaport et al, 1996 Zheng et al., 1997). Conversion of substituted hydroquinones such as p-aminophenol-hydroquinone and 2-bromo-hydroquinone to their respective glutathione S-conjugates must occur to allow bioactivation into nephrotoxic metabolites (Dekant, 1993). Western blot analysis of proteins from the kidneys of rats treated with 2-bromo-hydroquinone has revealed three distinct protein adducts conjugated to quinone-thioethers (Kleiner et al, 1998). 

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]. 

The actual synthesis (Scheme 10) commenced with the couphng of diene acid 54 and aminophenol 53 to provide diene amide 55. In situ generation of quinone monoimide 52 under oxidative conditions and subsequent intramolecular Diels-Alder (IMDA) reaction furnished an 8 1 mixture of endo/exo... 

The nephrotoxicity of bromobenzene (see chap. 7) and possibly 4-aminophenol is also believed to be due to the cysteine conjugates of the quinone or quinoneimine, respectively. Biliary excretion and reabsorption from the gut and delivery to the kidney is a crucial part of this process as it is with hexachlorobutadiene (chap. 7). 

The dediazoniation reaction is mainly dependent on the temperature, especially in the case of 4-aminophenol at low temperature 4-hydroxybenzenediazonium fluoride loses hydrogen fluoride to deliver a stable quinone-diazide which gives fluorophenol at 140°C only.93 The mechanisms involved in the synthesis of 4-fluorophenol are summarized in Scheme 5.93... 

Dediazoniation itself is not dramatically dependent on the hydrogen fluoride/pyridine ratio, as shown from the dediazoniation of benzenediazonium tetrafluoroborate (previously isolated) in hydrogen fluoride/pyridine mixtures provided that the hydrogen fluoride/pyridine ratio is larger than 6, fluorobenzene is always obtained in quantitative yield (for hydrogen fluoride/ pyridine ratios below 6, byproducts result from the phenyl cation and free pyridine).10 These observations have resulted in new, very efficient syntheses of 4-fluorophenols 2 involving dediazoniation, in hydrogen fluoride/pyridine mixtures, of crystalline 4-hydroxy benzenediazonium chloride and tetrafluoroborate 3 (formed under anhydrous conditions)89,96 as well as quinone-diazide (formed from aminophenol in tetrafluoroboric acid).93,97 Such methods are more efficient than the Balz-Schiemann reaction under standard conditions. 

Phenoxazin-3-ones and phenothiazin-3-ones can be prepared by condensation of 2-aminophenols or -thiols with quinones. Alizarin Green G (61), for example, is obtained from (59) and (60). Similarly, 2-aminothiophenols and 6-chloro-2-methoxy-l,4-benzoquinone (62) afford phenothiazin-3-ones (63). 

The potassium chlorate both oxidises and chlorinates. If chromic acid, or even weaker oxidising agents, is employed the dichloro-quinone is obtained. The oxidation of aminophenols is illustrated in the following, in which nitrous acid serves as oxidising agent. 

It has been found satisfactory to continue the extraction for 30 minutes after the volume of the aqueous phase no longer decreases visibly. Saturated aqueous sodium bicarbonate washes may be used to effect removal of the acetic acid from ether solutions of alkyl quinones. The cascade distribution apparatus devised by Kies and Davis4 is useful for this purpose. As halo-genated quinones have been found to be unstable to bicarbonate, the acetic acid must be removed before oxidation of the corresponding aminophenols. 

It has been found that the sulfates of the aminophenols may be obtained in yields about the same as those recorded for the quinones by concentrating the aqueous catholytes under reduced pressure after removal of the acetic acid. 

The present method is the result of a study by Cason, Harman, Goodwin, and Allen.6 7 The sequence of electrolytic reduction followed by oxidation has been used for the preparation of 5-bromotoluquinone,8 5-chlorotoluquinone,9 and 3-chlorotolu-quinone.10 The preparation of an intermediate />-aminophenol from the corresponding aromatic nitro compound by electrolytic reduction is a useful general method.11-18 Chloro-/>-quinone has been prepared by acid dichromate oxidation of chlorohydro-quinone 19-22 or 2-chloro-4-aminophenol.23 24 It has been shown that pure chloro-/>-quinone is obtained only with some difficulty when chlorohydroquinone is used.7... 

A fairly general procedure for the synthesis of o- and p-quinones consists in coupling a phenol with a diazonium salt and reducing the resulting azo compound to an aminophenol with sodium dithionite. Mild oxidation with, for example, iron(m) chloride results in the formation of the corresponding quinone (e.g. the preparation of 1,2-naphthoquinone described and formulated in Expt 6.131). 

Double oxidation reactions of aminophenols (127) to the corresponding quinone-imines (128) using PIDA and PIFA were utilized for total synthesis of an enediyne antibiotic, ( )-dynemicin A (6), by Danishefsky and co-workers... 

Despite the ionic reactions, other reactions (presented in Scheme 44) show that free-radical mechanisms can also take place. Catalyzed by ebselen, TBHP oxidation of alkylarenes to alkyl aryl ketones (141) [240], anthracene to anthraquinone (142), 1,4-dimethoxyarenes to 1,4-quinones (e.g., menadione 143) [244], and oxidative coupling of 2-aminophenol to phenoxazinone (144) [245] gave results similar to these when one-electron oxidants such as Ce(IV), Ag(II), or Mn(III) were the reagents. Moreover, oxidation of azine derived from 2-acetylpyridine gave a mixture of ketone (145) and condensed triazole (146) [240], The same result was found when cerium ammonium nitrate was used as the reagent. This suggests that the... 

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