0-Aminophenols, synthesis

Aichaoui H, Lesieur I, Henichart JP (1990) Unequivocal preparation of 4- and 5-acyl-2-aminophenols. Synthesis 679-680... 

Ammonium nitrate N-lauroyl-p-aminophenol synthesis Lauroyl chloride N-methylpyrrole mfg. 

Uses. (9-Nitrochlorobenzene is used in the synthesis of azo dye intermediates such as o-chloroaniline (Fast YeUow G Base), i9-nitroani1ine (Fast Orange GR Base), o-anisidine (Fast Red BB Base), o-phenetidine, and (9-aminophenol (see Azo dyes). It also is used in corrosion inhibitors, pigments, and agriculture chemicals. -Nitrochlorobenzene is used principally in the production of intermediates for azo and sulfur dyes. Other uses include pharmaceuticals (qv), photochemicals, mbber chemicals (qv), and insecticides (see Insectcontroltechnology). Typical intermediates manufactured from the para isomer are -lutioaruline (Fast Red GC Base), anisidine, -aminophenol, -nitrophenol, -phenylenediamine, 2-chloro-/)-anisidine (Fast Red R Base), 2,4-dinitrochlorobenzene, and l,2-dichloro-4-nitrobenzene. 

Substitution of various groups by amino or hydroxyl functions is industrially unimportant for the production of 2- and 4-aminophenol, but this type of reaction is used for the synthesis of 2- and 4-aminophenol derivatives. However, 3-aminophenol caimot be obtained easily by reduction. It is made by the reaction of 3-aminobenzenesulfonic acid [121 -47-1] with sodium hydroxide under fusion conditions (5—6 h 240—245°C). The product is purified by vacuum distillation (25). 

The direct conversion of aniline into aminophenols may be achieved by hydrogen peroxide hydroxylation in SbE —HE at —20 to —40° C. The reaction yields all possible aminophenols via the action of H20" 2 on the anilinium ions the major product is 3-aminophenol (64% yield) (70,71). This isomer may also be made by the hydrolysis of 3-aminoaniline [108-45-2] in dilute acid at 190°C (72). Another method of limited importance, but useful in the synthesis of derivatives, is the dehydrogenation of aminocyclohexenones (73). 

Teratogenic effects have been noted with 2- and 4-aminophenol in the hamster, but 3-aminophenol was without effect in the hamster and rat (129,130). 4-Aminophenol is known to inhibit DNA synthesis and alter DNA stmcture in human lymphoblasts (131,132) and is mutagenic in mouse micronuclei tests (133). The aminophenols have been shown to be genotoxic, as evidenced by the induction of sister chromatid exchanges (134,135), but they also exert a protective effect against DNA interaction with other noxious chemicals (136). After assessment of available data a recent report stated that the aminophenols were safe as cosmetic ingredients in their present uses and concentrations (137). 

The aminophenols are versatile intermediates and their principal use is as synthesis precursors their products are represented among virtually every class of stain and dye. 

The derivatives of the aminophenols have important uses both in the photographic and the pharmaceutical industries. They are also extensively employed as precursors and intermediates in the synthesis of more compHcated molecules, especially those used in the staining and dye industry. All of the major classes of dyes have representatives that incorporate substituted aminophenols these compounds produced commercially as dye intermediates have been reviewed (157). Details of the more commonly encountered derivatives of the aminophenols can be found in standard organic chemistry texts (25,158). A few examples, which have specific uses or are manufactured in large quantities, are discussed in detail in the following (see Table 6). 

A Methylamino)phenol. This derivative, also named 4-hydroxy-/V-methy1ani1ine (19), forms needles from benzene which are slightly soluble in ethanol andinsoluble in diethyl ether. Industrial synthesis involves decarboxylation of A/-(4-hydroxyphenyl)glycine [122-87-2] at elevated temperature in such solvents as chlorobenzene—cyclohexanone (184,185). It also can be prepared by the methylation of 4-aminophenol, or from methylamiae [74-89-5] by heating with 4-chlorophenol [106-48-9] and copper sulfate at 135°C in aqueous solution, or with hydroquinone [123-31 -9] 2l. 200—250°C in alcohoHc solution (186). 

Both 5-hydroxyquiQoline [578-67-6] and S-hydroxyquiaoline [148-24-3] have been prepared ia good yields by the acid hydrolysis of the appropriate aminoquiaoline at temperatures of 180—235°C (124). The latter compound has been prepared ia several different ways, including sulfonation-fusion of quiaoline. Hydrolysis of 8-chloroquinoline [611-33-6] gives a 93% yield, whereas 80% is obtained ia a modified Skraup synthesis with o-aminophenol (125,126). 

The method developed for preparation of telluradiazines 89 was applied to the synthesis of benzo derivatives of l-oxa-2-tellura-6-azacycloocta-3,5-diene 100 (99UP2). It involves dehydrobromination of bromotellurenylvinylaldimines 101, obtained by condensation of 2-methyldibromotellurocyclohexenealdehyde with o-aminophenols. Under a treatment of benzene suspension of 101 with triethyl-amine followed by short-term refluxing the reaction mixture the heterocycles 100 were obtained in 71-87% yields. 

Hydrogenolysis of methylenediisoxazoles have been useful in preparing substituted resorcinols and aminophenols (7). The isoxazole annelation reaction (71,89,90,91,103) is well suited to the synthesis of steroids and other complex molecules. 

A direct catalytic conversion of esters, lactones, and carboxylic acids to oxazolines was efficiently achieved by treatment with amino alcohols in the presence of the tetranuclear zinc cluster Zn4(0C0CF3)60 as catalyst, essential for condensation and cyclodehydration reactions. For example, the use of (5)-valinol allowed the easy synthesis of oxazolines 125 and 126 in satisfactory yields <06CC2711>. A one-pot direct preparation of various 2-substituted oxazolines (as well as benzoxazoles and oxadiazoles) was also performed from carboxylic acids and amino alcohols (or aminophenols or benzhydrazide) using Deoxo-Fluor reagent <06TL6497>. 

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. 

For the synthesis of benzoxazoles, Player and coworkers have developed a simple method that involves microwave heating of a 2-aminophenol with 1.1 equivalents of an acid chloride in dioxane or xylene (Scheme 6.213) [384]. The best results were... 

Efficient synthesis of 7-aminocoumarins has been performed via the Pechmann reaction between m-aminophenols and /i-ketonic esters. A comparative study of this procedure showed that use of microwave irradiation reduced the reaction time from several hours, if conventional heating was used, to a few minutes only (Eq. 22) [75]. 

This intramolecular etherification approach has successfully been applied to the syntheses136 of siccanin137 and clusifoliol,136 and a formal synthesis of morphine.138 Examples of tandem inter- and intramolecular etherification reactions have also been reported which convert catechol and o-aminophenol derivatives into benzodioxins (Equation (24)),139-141 benzodioxepines,142 and morpholines.139,140... 

Three major approaches have been followed to provide reactive dyes in this important sector. One category is closely related to the reddish blue monoazo 1 1 copper complexes already described (section 7.5.8). To provide the higher substantivity and deeper intensity for build-up to navy blue shades, a second unmetallised azo grouping is introduced. As with the brown dyes, the A—>M—>E pattern is adopted for their synthesis. Component A is normally a sulphonated aniline, M an aminophenol or aminocresol and E a sulphonated naphthol or aminonaphthol. The reactive system (Z) is usually, but not invariably, located on the E component and the copper atom always coordinates with an o,o -dihydroxyazo grouping provided by the M and E components (7.109). 

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 synthesis of the bis(amino) aryl ether ketimine oligomer was carried out in an analogous fashion to the poly(aryl ether) oligomers described before (Scheme 5) [43]. The ketimine functional 4,4 -bisfluoride was reacted with hyd-roquinone and 3-aminophenol in an NMP/toluene solvent mixture in the presence of potassium carbonate. The characteristics of the oHgomer synthesized are shown in Table 1 (sample le). 

The different reactivities associated with nucleophiles and leaving groups is nicely exemplified in the synthesis of the analgesic drug paracetamol (USA acetaminophen) from 4-aminophenol. If 4-aminophenol is treated with an excess of acetic anhydride, aeetylation of both amino and phenol groups is observed, and the product is the diacetate. Paracetamol is the A-acetate of 4-aminophenol, so how might mono-acetylation be achieved There are two approaches. 

Many other possibilities can be conceived by positioning the aryl halide into another component. Figure 18 shows the synthesis of dibenzoxazepines 90 starting from o-aminophenols and from o-chloro-p-nitrobenzaldehyde 88 [60]. 

N-Aminooxazolidone, 228 6-Aminopenicillanic acid (6-APA), 409, 410 Aminophenazole, 248 p-Aminophenol, 111 Aminophylline, see theophylline Amlnopromazine, 390 Aminopropylon, 234 2-Aminopyrimidine synthesis, 127, 128... 

Aminophenols from anilines, 35, 2 Anhydrides of aliphatic dibasic acids, Friedel-Crafts reaction with, 5, 5 Anion-assisted sigmatropic rearrangements, 43, 2 Anthracene homologs, synthesis of, 1, 6 Anti-Markownikoff hydration of alkenes, 13, 1... 

Iodoquinol Iodoquinol, 5,7-diiodo-8-quinolinol (37.2.2), is made by iodination of 8-oxyquinoline (37.2.1) using a mixture of potassium iodide/potassium iodate. The initial 8-hydroxyquinolin (37.2.1) is made from 2-aminophenol and glycerol in the presence of sulfuric acid and nitrobenzene (Skraup synthesis) [39,40]. 

Murakami et al. reported the total synthesis of 1-hydroxy-3-methylcarbazole (23) and murrayafoline A (7) by classical Fischer indolization of the O-methanesulfonyl phenylhydrazone derivative 614 (575). The compound 614 was prepared from the corresponding aminophenol 612 via 2-hydrazino-5-methylphenol p-toluenesulfonate... 

Routes to benzoxadiazoles are based on approaches to the tautomeric 6-diazo-2,4-cyclo-hexadienones (Scheme 11) <9UST(247)135>. The appropriate 2-aminophenol hydrochloride is diazo-tized using either sodium nitrite or isoamyl nitrite and the diazonium chloride is then carefully neutralized with sodium carbonate or potassium carbonate. An alternative approach is from the monotosylhydrazone of the appropriate o-benzoquinone. Naphthoxadiazole (6) was prepared, in a manner analogous to the first route of Scheme 11, from 3-amino-2-naphthol <91AG(E)1476>. A slightly modified preparation is described in a later paper the method was applied to the synthesis of [9a- C]naphth[2,3-( ]-l,2,3-oxadiazole from 3-amino-[2- C]-2-naphthol <92Mi 403-03>. 

Reactions of this type have been widely used for the synthesis of 1,5-benzoxazepines by the reactions of o-aminophenols and their derivatives with a variety of functionalized three-carbon chains. Thus reaction with 3-bromo-l-chloropropane gives (360) and reaction with 3-chloropropionyl chloride gives the analogous 4-oxo derivative. Similarly a,/3-unsatur-ated Icetones give (361), /3-ketoesters give (362), l,3-oxazolid-5-ones give (363), and the reaction of the sodium salt of N-methanesulfonyl-o-aminophenol with epichlorohydrin gives... 

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