In aminophenols

In aminophenols, the amino and hydroxyl groups retain their individual properties, each group having little influence on the other. It is possible, therefore, under certain conditions to salt out the sodium salt from a solution of the aminophenol containing excess alkali, or the hydrochloride from a solution containing hydrochloric acid. The free aminophenol itself can be separated from neutral, ammoniacal, bicarbonate, or acetic acid solutions. 

Two positions are potentially reactive in aminophenols, but the amino group directs the orientation of the entering group in thiocyanation. An example is the conversion of o-aminophenol into 4-thiocyano-2-hy-droxyaniline in 50% yield. 

Bright yellow needles m.p. 45 C, b.p. 2 4°C. Prepared together with 4-nitrophenol by careful nitration of phenol. Sodium sulphide reduces it to 2-aminophenol which is used in dyestuffs and photographic processes. 

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. 

A) Benzoyl Derivative. Since acetylation and benzoylation do not always proceed smoothly with nitrophenols, it is best to reduce them to the aminophenol as in (3) above. Add an excess of 20% aqueous sodium hydroxide to the reaction mixture after reduction, cool and then add a small excess of benzoyl chloride, and shake in the usual way. The dibenzoyl derivative wiU separate. Filter, wash with water and recrystalUse. (M.ps., p. 551.)... 

This extremely reactive substance rearranges, in the presence of acids, with the production of />-aminophenol ... 

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. 

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 ... 

Place 170 ml. of concentrated sulphuric acid in a 1-litre three necked flask provided with a stirrer, and add 112 - 5 g. of o-aminophenol, followed by 287 g. of glycerol maintain the temperature below 80° by cooling, if necessary. Keep the mixture in a fluid state by placing the flask on a steam bath. 

Phenacetin may be conveniently prepared in the laboratory from p-amino-phenol. The latter is readily acetylated with acetic anhydride to give p-acetyl-aminophenol this Is ethylated in the form of the sodio derivative to yield acetyl p-phenetidine (phenacetin) ... 

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. 

The carbonyiation of o-diiodobenzene with a primary amine affords the phthalimide 501 [355,356]. Carbonyiation of iodobenzene in the presence of (9-diaminobenzene (502) and DBU or 2,6-lutidine affords 2-phenylbenzimida-zole (503)[357, The carbonyiation of aryl iodides in the presence of pentaflnor-oaniline affords 2-arylbenzoxazoles directly, 2-Arylbenzoxazole is prepared indirectly by the carbonyiation of (9-aminophenol[358j. The optically active aryl or alkenyl oxazolinc 505 is prepared by the carbonyiation of the aryl or enol triflates in the presence of the opticaly active amino alcohol 504, followed by treatment with thionyl chloride[359]. 

The use of an amperometric detector is emphasized in this experiment. Hydrodynamic voltammetry (see Chapter 11) is first performed to identify a potential for the oxidation of 4-aminophenol without an appreciable background current due to the oxidation of the mobile phase. The separation is then carried out using a Cjg column and a mobile phase of 50% v/v pH 5, 20 mM acetate buffer with 0.02 M MgCl2, and 50% v/v methanol. The analysis is easily extended to a mixture of 4-aminophenol, ascorbic acid, and catechol, and to the use of a UV detector. 

Bis(benZoxaZol-2-yl) Derivatives. Bis(benzoxazol-2-yl) derivatives (8) (Table 3) aie prepared in most cases by treatment of dicaiboxyhc acid derivatives of the central nucleus, eg, stilbene-4,4Cdicarboxyhc acid, naphthalene-l,4-dicarboxyhc acid, thiophene-2,5-dicarboxyhc acid, etc, with 2 moles of an appropriately substituted o-aminophenol, followed by a ring-closure reaction. These compounds are suitable for the brightening of plastics and synthetic fibers. 

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). 

Also present but not essential in permanent hair colorants are nitro dyes which dye hair without oxidation. These dyes, nitro derivatives of aminophenols and benzenediamines, impart yellow, orange, or red tones. Although they have good tinctorial value, they are not as colorfast as the oxidative dyes. They also are used in semipermanent hair colorants. 

Resorcinol Derivatives. Aminophenols (qv) are important intermediates for the syntheses of dyes or active molecules for agrochemistry and pharmacy. Syntheses have been described involving resorcinol reacting with amines (91). For these reactions, a number of catalysts have been used / -toluene sulfonic acid (92), zinc chloride (93), zeoHtes and clays (94), and oxides supported on siUca (95). In particular, catalysts performing the condensation of ammonia with resorcinol have been described gadolinium oxide on siUca (96), nickel, or zinc phosphates (97), and iron phosphate (98). 

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. 

Electrolytic reductions generally caimot compete economically with chemical reductions of nitro compounds to amines, but they have been appHed in some specific reactions, such as the preparation of aminophenols (qv) from aromatic nitro compounds. For example, in the presence of sulfuric acid, cathodic reduction of aromatic nitro compounds with a free para-position leads to -aminophenol [123-30-8] hy rearrangement of the intermediate N-phenyl-hydroxylamine [100-65-2] (61). 

Aminophenols and their derivatives are of commercial importance, both in their own right and as intermediates in the photographic, pharmaceutical, and chemical dye industries. They are amphoteric and can behave either as weak acids or weak bases, but the basic character usually predominates. 3-Aminophenol (2) is fairly stable in air unlike 2-aminophenol (1) and 4-aminophenol (3) which easily undergo oxidation to colored products. The former are generally converted to their acid salts, whereas 4-amiaophenol is usually formulated with low concentrations of antioxidants which act as inhibitors against undesired oxidation. 

Table 2. In acidic solution all isomers exhibit fluorescence. 4-Aminophenol shows two bands one at 300 nm common to all the isomers, and the second at 370 nm attributed to the existence of an additional aqueous ionic species. Fluorescence also exists in neutral solution, but is aboHshed at high pH values (3-13).

Table 1. Solubility of Aminophenols in Common Solvents Arranged in Order of Increasing Polarity (Dielectric Constant)...

Aminophenol. This compound forms white plates when crystallized from water. The base is difficult to maintain in the free state and deteriorates rapidly under the influence of air to pink-purple oxidation products. The crystals exist in two forms. The a-form (from alcohol, water, or ethyl acetate) is the more stable and has an orthorhombic pyramidal stmcture containing four molecules per unit cell. It has a density of 1.290 g/cm (1.305 also quoted). The less stable P-form (from acetone) exists as acicular crystals that turn into the a-form on standing they are orthorhombic bipyramidal or pyramidal and have a hexamolecular unit (15,16,24) (see Tables 3—5). 

The chemical properties and reactions of the aminophenols and their derivatives are to be found in detail in many standard chemical texts (25). The acidity of the hydroxyl function is depressed by the presence of an amino group on the benzene ring this phenomenon is most pronounced with 4-aminophenol. 

Acylation. Reaction conditions employed to acylate an aminophenol (using acetic anhydride in alkaU or pyridine, acetyl chloride and pyridine in toluene, or ketene in ethanol) usually lead to involvement of the amino function. If an excess of reagent is used, however, especially with 2-aminophenol, 0,A/-diacylated products are formed. Aminophenol carboxylates (0-acylated aminophenols) normally are prepared by the reduction of the corresponding nitrophenyl carboxylates, which is of particular importance with the 4-aminophenol derivatives. A migration of the acyl group from the O to the N position is known to occur for some 2- and 4-aminophenol acylated products. Whereas ethyl 4-aminophenyl carbonate is relatively stable in dilute acid, the 2-derivative has been shown to rearrange slowly to give ethyl 2-hydroxyphenyl carbamate [35580-89-3] (26). 

Condensation Reactions. Condensation of substituted ben2aldehydes with 2-aminophenol in the presence of a catalyst (aluminum, iron,... 

Aminophenols are either made by reduction of nitrophenols or by substitution. Reduction is accompHshed with iron or hydrogen in the presence of a catalyst. Catalytic reduction is the method of choice for the production of 2- and 4-aminophenol (see Amines BY reduction). Electrolytic reduction is also under industrial consideration and substitution reactions provide the major source of 3-aminophenol. 

Iron Reduction. The reduction of nitrophenols with iron filings or turnings takes place in weakly acidic solution or suspension (30). The aminophenol formed is converted to the water soluble sodium aminopheno1 ate by adding sodium hydroxide before the iron-iron oxide sludge is separated from the reaction mixture (31). Adjustment of the solution pH leads to the precipitation of aminophenols, a procedure performed in the absence of air because the salts are very susceptible to oxidation in aqueous solution. 

The chemical production of aminophenols via the reduction of nitrobenzene occurs in two stages. Nitrobenzene [98-95-3] is first selectively reduced with hydrogen in the presence of Raney copper to phenylhydroxylamine in an organic solvent such as 2-propanol (37). With the addition of dilute sulfuric acid, nucleophilic attack by water on the aromatic ring of /V-phenylhydroxylamine [100-65-2] takes place to form 2- and 4-aminophenol. The by-product, 4,4 -diaminodiphenyl ether [13174-32-8] presumably arises in a similar manner from attack on the ring by a molecule of 4-aminophenol (38,39). Aniline [62-53-3] is produced via further reduction (40,41). 

In another process variant, only 88% of the nitrobenzene is reduced, and the reaction mixture then consists of two phases the precious metal catalyst (palladium on activated carbon) remains in the unreacted nitrobenzene phase. Therefore, phase separation is sufficient as work-up, and the nitrobenzene phase can be recycled direcdy to the next batch. The aqueous sulfuric acid phase contains 4-aminophenol and by-product aniline. After neutralization, the aniline is stripped, and the aminophenol is obtained by crystallization after the aqueous phase is purified with activated carbon (53). 

In an alternative industrial process, resorcinol [108-46-3] is autoclaved with ammonia for 2—6 h at 200—230°C under a pressurized nitrogen atmosphere, 2.2—3.5 MPa (22—35 atm). Diammonium phosphate, ammonium molybdate, ammonium sulfite, or arsenic pentoxide maybe used as a catalyst to give yields of 60—94% with 85—90% selectivity for 3-aminophenol (67,68). A vapor-phase system operating at 320°C using a siUcon dioxide catalyst impregnated with gallium sesquioxide gives a 26—31% conversion of resorcinol with a 96—99% selectivity for 3-aminophenol (69). 

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