Coupling Aminophenols

A fairly general procedure consists in coupling a phenol or naphthol with a diazotised amine, reducing the product to an aminophenol or aminonaphthol, and oxidising the hydroxy compound with acid ferric chloride solution. This method is illustrated by the preparation of (3 (or 1 2)-naphthoquinone ... 

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). 

Acid YeUow 23 (31), commonly known as Tartraziae, stiU maintains sales of nearly 0.5 million /yr ia the United States. It was first discovered ia 1884 and is made by coupling equimolar quantities of diazotized sulfarulic acid to 3-carboxy-l- -sulfophenyl)-5-pyrazolone. Other monoazopyrazolone dyes of commercial importance iaclude Acid YeUow 17 (32) (sulfarulic acid — l-(2,5-dichloro-4-sulfophenyl)-3-methyl-5-pyrazolone and Acid YeUow 40 [6372-96-9] (33) (Cl 18950) (p-aminophenol l-(4-chloro-2-sulfophenyl)-3-methyl-5-pyrazolone) foUowed by esterification of the phenoUc hydroxy group with -toluenesulfonyl chloride. 

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... 

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... 

Phenols and amines capable of coupling [4, 8] e.g. aniline derivatives, aminophenols [5]... 

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

Goebel, W.F., Babers, F.H., and Avery, O.T. (1932) Chemo-immunological studies on conjugated carbohydrate-proteins VI. The synthesis of p-aminophenol alpha-glucoside and its coupling with protein. J. Exp. Med. 55(5), 761-767. 

Aminophenol is a useful dyestuff intermediate, capable of coupling in either the 2- or the... 

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. 

For aminophenols, one-electron oxidation and the proton elimination can run together in one stage. This leads to a cation-radical containing O and +NH3 fragments within one and the same molecular carcass (Rhile et al. 2006). Such concerted reactions are classified as proton-coupled electron transfer (Mayer 2004). Proton-coupled electron transfer differs from conventional one-electron redox reaction in the sense that proton motion affects electron transfer. Because the transfers of a proton and an electron proceed in a single step, we can say about the hydrogen-atom transference, (H+ -I- e)=H. It is the fundamental feature of proton-coupled electron-transfer reactions that the proton and electron are transferred simultaneously, but from different places (see Tanko 2006). 

An excellent survey of the various methods of synthesis is available53 this section includes some of the illustrative methods of synthesis of the simpler analogues. These methods may be considered under the following headings (a) the oxidation of hydrocarbons (b) the oxidation of phenols and the oxidative coupling of phenols (c) the oxidation of dihydric phenols and aminophenols and (d) the cyclisation of aroylbenzoic acids. 

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). 

Following the same strategy, Landis prepared the l,l -ferrocenyldi-phosphines 53a-c featuring pendant benzoxaborolidine moieties (Scheme 33). 63 Reaction of 2-aminophenol with the ferrocene precursor 51 afforded 52 which was subsequently coupled with various boronic acids to give compounds 53a-c in good yields. Monomeric open structures were supported by 31P NMR spectroscopy and crystallography for 53a. 

One of the starting materials, the bromoindolinemesylate 183 was obtained from the commercially available 5-hydroxyindole by mesylation followed by successive treatment of the resulting indole derivative with sodium cyanoborohydride and bromine. Coupling of 183 with the known boronic acid 184 in the presence of zero valent palladium complex led directly to the lactam 185, the intermediate carbinolamine 186 formed initially in the reaction suffering facile aerial oxidation during work-up. On reduction with sodium (2-methoxyethoxy)aluminium-hydride, the amide 185 yielded the aminophenol 187 which on chromatography underwent oxidative aromatisation to 182 in 54% yield. 

It has been shown by using NMR spectroscopy in conjunction with isotopelabelling studies that there is a significant degree of deacetylation followed by reacetylation (futile deacetylation) of paracetamol metabolites in vivo in the rat [58]. If this also occurs in humans, then it may help to explain the observed incidence of nephrotoxicity of paracetamol in that the process would result in levels of the potent nephrotoxin 4-aminophenol in vivo. Confirmation of the levels of futile deacetylation in individual metabolites of isotopically labelled paracetamol in man has been achieved by using directly coupled HPLC-NMR... 

In alkaline medium m-aminophenol couples at the position para to the hydroxyl group in an acid solution /i-hydroxy and / -aminoazo dyes are obtained. 

Dealkylative and oxidative coppering and subsequent demetallation in aqueous mineral acids are technical processes to prepare o.o -dihydroxyazo compounds, which are not available from o-aminophenols by diazotation and coupling reactions. 

Metallization. Bident ate formazans that are insoluble in water can be warmed with cobalt, nickel, and copper salts (preferably acetates) to form metal chelates in solvents such as methanol, ethanol, acetone, and dimethylformamide. Metal complexes of tri- and tetradentate formazans are much more stable. Metallization with divalent salts occurs rapidly at room temperature. On reaction with diazo-tized 2-aminophenols or 2-aminonaphthols, coupling and metallization with divalent metal salts can take place concurrently under the same conditions. When coupling is complete, the dye is usually fully metallized. 

C.I. Acid Yellow 76, 18850 [6359-88-2] (14), is obtained by coupling diazotized 4-aminophenol onto the pyrazolone component and then esterifying with -toluene-sulfonic acid chloride in an alkaline medium. The toluenesulfonic ester group substantially improves the fastness to milling and makes the shade obtained largely independent of pH the lightfastness is not quite as good as that of C.I. Acid Yellow 17. 

In the synthesis of the unsymmetrical 1 2 cobalt complex 18 [68928-31-4] [30], the 1 1 cobalt complex 17 and the azo dye made by coupling of 1-acetoacetyl-amino-2-ethylhexane with diazotized 2-aminophenol-4-sulfonamide are intro-... 

Oxidation. A primary intermediate, i.e., a para-substituted aromatic compound such as a derivative of 1,4-diaminobenzene or of 4-aminophenol, is oxidized to a quinonediimine or quinonemonoimine, respectively. The imine then reacts with a secondary intermediate (coupler), which is a meta-substituted compound such as as a derivative of 1,3-diaminobenzene, 3-aminophenol, or resorcinol. Another oxidation step yields an indo, phenazine, or oxazine dye which is three times the size of the precursors. The mechanism of this coupling reaction is shown in Scheme 5.1. 

---