Amino-4-nitrophenol

Submitted by W. W. Hartman and H. L. Silloway. Checked by H. R. Snyder and J. Wayne Kneisley. 

In a 5-1. three-necked flask, suspended over a steam bath, are placed 300 g. (1.63 moles) of technical 2,4-dinitrophenol and 2.51. of water. The flask is fitted with an efficient stirrer, a reflux condenser, and a thermometer which dips below the surface of the mixture. After the stirrer has been started, 600 g. (11.6 moles) of ammonium chloride and 100 ml. of concentrated aqueous ammonia (about 28%) are added, and the mixture is heated to 85°. The steam is turned off, and the mixture is allowed to cool. When the temperature reaches 70° (Note 1), 700 g. (5.4 moles) of 60% fused sodium sulfide is added in portions of about 100 g. at 5-minute intervals. After two or three such additions the temperature of the reaction mixture reaches 80-85° it is kept in this range either by adding the remaining portions of sodium sulfide at 10-minute intervals or by wrapping the flask with a wet cloth and continuing the additions at 5-minute intervals. After all the sodium sulfide has been added, the reaction mixture is 

The hot filtrate is transferred to a 5-1. round-bottomed flask and cooled overnight by a stream of cold water. The mixture is filtered, and the crystals are pressed nearly dry. The solid is dissolved in 1.5 1. of boiling water, and the solution is acidified with glacial acetic acid (about 100 ml. is required, Note 3). The solution is heated with 10 g. of Norite, filtered hot, and cooled to 20°. The brown crystals are collected and dried for several hours in an oven at 65° or in a vacuum desiccator (Note 4). The yield of 2-amino-4-nitrophenol melting at 140-142° is 160-167 g. (64-67%). If a purer product is desired, the crude substance is recrystallized from 1.5 1. of hot water 147-153 g. (58-61%) of material melting at 142-143° is obtained. 

If the reaction is run at temperatures below 70° it is impossible to obtain a pure product even after several recrystallizations. 

The amount of acid required varies with dryness of the filter cake. The acidification can be followed by observing the color of a thin layer of the solution splashed against the side of the container. The color changes from dark red to olive brown at the end point. Both colors are so deep that they are not easily distinguished except when thin layers are viewed. After the end point is observed, an additional 10 ml. of acetic add is added. 

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Amino-4-nitrophenol. This derivative, 2-hydroxy-5-nitroani1ine (9), forms orange prisms from water. These prisms are hydrated with one water of crystallization, mp 80—90°C, and can be dehydrated over sulfuric acid to the anhydrous form, mp 143 —145°C. The compound is soluble in ethanol, diethyl ether, acetic acid, and warm benzene and slightly soluble in water. 

The metabolism of an oral dose of 50-100 mg/kg "C-1,3-DNB was followed in rabbits (Parke 1961). Of the metabolites detected in urine, 30% were conjugated with glucuronic acid and 6% with sulfate. The major urinary metabolites of 1,3-DNB were 2,4-diaminophenol (31%), 1,3-phenylenediamine (25%), 1,3-nitroaniline (18%), and 2-amino-4-nitrophenol (14%). Other minor metabolites comprising about 20% of the label were oxidation and reduction products and azoxy dimers. 

Amino-l-methyl-527-pyrido[4,3-6]indole (see Trp-P-2) 2-Amino-5-(5-nitro-2-furyl)-l,3,4-thiadiazole 2-Amino-4-nitrophenol 2-Amino-5-nitrophenol... 

Knowledge of the enzymes used by microorganisms in the transformation of nitroaromatic compounds is limited. Blasco Castillo (1993) characterized an inducible nitrophenol reductase from Rhodobacter capsulatus that catalyzed the reduction of 2,4-dinitrophenol (DNP) to 2-amino-4-nitrophenol. This enzyme was a dimer that contained flavin mononucleotide and possibly nonheme iron as... 

Amino-4-nitrophenol has been prepared by the partial reduction of 2,4-dinitrophenol chemically -6 and electrolytically,6 and by the action of sulfuric add on 3-nitroazidobenzene.7... 

Colorants for other purposes, such as hair dyes, are not so strictly regulated. The ones used in semi-permanent dyes are 2-nitro-i,4-diaminobenzene, (orange/red), 2-amino-4-nitrophenol (yellow), 1,4-diaminoanthraquinone (violet), and 1,4,5,8-tetra-aminoanthaquinone (blue), and a combination of these will produce the desired shade. 

Amino-4-nitrophenol, 25, 5 2-Amino-5-nitrotoluene, 20, 73 22, 44 (7/-ar-AMINOPHENYL ACETIC ACID, 22, 23 df-a-AMINO-a-PHENYLPROPIONIC ACID,... 

Martin [32] found that dinitrophenol undergoes in the body a partial reduction either to 2-amino-4-nitrophenol or to 4-amino-2-nitrophenol Mid 2,4-diamino-phenol. Part of the compound is excreted unchMiged in the wine. 

Gallic acid resorcinol 2,4-dinitroresorcinol 2-amino-4-nitrophenol Competitive inhibitors [77]... 

Aromatic dinitro compounds may be selectively reduced by hydrazine in the presence of transition metal catalysts.136 Pitre and Lorenzotti obtained 3-amino-5-nitrobenzoic acid in 82% yield by treating 3,5-dinitrobenzoic acid with Raney Ni and an appropriate amount (3.6 equiv) of hydrazine in water (eq. 9.57).137 Similarly, 2,4-dinitrophe-nol and 2,4-dinitroaniline were reduced to 2-amino-4-nitrophenol and 2-amino-4-nitroaniline, respectively, with 10% Pd-C and hydrazine in ethanol solution. 

Problem 24.8 The //-propyl ether of 2-amino-4-nitrophenol is one of the sweetest compounds ever prepared, being about 5000 times as sweet as the common sugar sucrose. It can be made from the dinitro compound by reduction with ammonium bisulfide. Outline the synthesis of this material starting from benzene or toluene and any aliphatic reagents. 

In humans, dogs, and rats, 2-amino-4-nitrophenol was found to be the major excretory product. Humans can slowly eliminate both the unchanged compound and the previously mentioned metabolites. Urinary excretion is considered to be the main route of elimination of dinitrophenols. The half-life in the serum of a severely poisoned farmer was calculated to be 13.5 days. The residence half-life in humans is estimated to be 5-14 days. The elimination half-life for dinitrophenols in mice was 6 h. 

DNP can be measured in blood, urine, and several body tissues. The main breakdown product of DNP in people, 2-amino-4-nitrophenol, can also be measured in the blood, urine, and tissues. The Derrien test is routinely used to measure this breakdown product in urine. This test produces a purple color if 2-amino-4-nitrophenol is present, but similar chemicals can also produce a purple color with this test. The total amount or concentration of DNP and its main breakdown products in urine or blood is a better indicator of DNP exposure. More modern tests can now identify and measure total DNP and breakdown products in blood or urine. However, these tests are not routinely available at your doctor s office, but can be performed at special laboratories or hospitals. These tests have not been used to tell exactly how much DNP people were exposed to or for how long. They also have not been used to predict harmful effects. More information on medical tests can be found in Chapters 2 and 6. 

No quantitative data were located regarding absorption in humans after inhalation exposure to DNPs. A metabolite of 2,4-DNP, 2-amino-4-nitrophenol, was commonly detected by the Derrien test in the urine of workmen (women were generally not employed in dangerous processes) exposed via inhalation to vapor and airborne dust of 2,4-DNP and by direct contact of the skin with the solid chemical in the munitions industry in France (Perkins 1919). Exposure may have occurred by the dermal and possibly oral routes, as well as by inhalation. In addition, examination of the blood, unspecified organs, and urine of workmen in this industry who died from exposure to 2,4-DNP revealed the presence of 2,4-DNP and its metabolites quantitative data were not provided (Perkins 1919). Despite its limitations, the study provides some evidence of absorption from inhalation exposure. 

DNP in the U.S. chemical industry, the urine contained 2.08 g/L of 2,4-DNP and 50 mg/L of 2-amino-4-nitrophenol (Gisclard and Woodward 1946). Workroom air levels of 2,4-DNP, determined subsequent to the death, were "normally" >40 mg/m. This may underestimate breathing-zone levels, and significant dermal absorption was thought to have occurred following deposition of the chemical on the skin. Hence, no conclusions regarding fraction absorbed can be drawn from this study, but it does provide additional evidence of absorption from the inhalation route. 

DNP and its reduced metabolites (not further specified) (Perkins 1919). The compounds found in urine were 2,4-DNP, 2-amino-4-nitrophenol, 4-amino-2-nitrophenol, 2,4-diaminophenol, and other unidentified nitrogen compounds, which may have been glucuronide conjugation products (NRC 1982). In cases of serious 2,4-DNP poisoning, the presence of large amounts of 2-amino-4-nitrophenol in the urine were found and were the basis of a particular test called the Derrien test, used as an indicator of exposure to 2,4-DNP. This test is a color reaction for... 

A woman who ingested sodium 2,4-DNP at 3.5 mg/kg day 2,4-DNP for 20 days tested positive for the presence of 2-amino-4-nitrophenol (Derrien test) and 2,4-DNP ("indicator test" not further described) in the urine (Davidson and Shapiro 1934). 

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