7?-Nitroaniline

Preparation of m-Nitroaniline (Section 600).—In a 100-cc. flask dissolve 10 grams of m-dinitrobenzene in 50 cc. of hot alcohol cool the solution under running water so that small crystals are formed, and add 10 cc. of a concentrated solution of ammonia in water. HOOD.—Pass into the solution a rapid stream of hydrogen sulphide as long as heat is evolved by the reaction (Eq.) this requires about one-half hour. Heat on the steam-bath for 10 minutes. Pour the product into 200 cc. of water, filter by suction, and wash the precipitate with water. Put the mixture of m-nitroaniline and sulphur into a beaker, add 100 cc. of water and 20 cc. of concentrated hydrochloric acid, stir, and filter off the residue of sulphur by suction. Set the filtrate 

Heat a mixture of 16 g. of p-nitroacetanihde and 75 ml. of 70 per cent, sulphuric acid (1) under a reflux water condenser for 20-30 minutes or until a test sample remains clear upon dilution with 2-3 times its volume of water. The p-nitroaniline is now present in the hquid as the sulphate. Pour the clear hot solution into 600 ml. of cold water and precipitate the p-nitroaniline by adding excess of 10 per cent, sodium hydroxide solution or of concentrated ammonia solution. When cold (cool the mixture in ice water, if necessary), filter the yellow crystalline precipitate at the pump, wash it well with water, and drain thoroughly. Recrystallise it from a mixture of equal volumes of rectified (or methylated) spirit and water or from hot water. Filter, wash and dry. The yield of p-nitro-anihne, m.p. 148°, is 11 g. 

The benzoyl compounds frequently occlude traces of unchanged benzoyl chloride, which thus escape hydrolysis by the caustic alkali it is therefore advisable, wherever possible, to recrystallise the benzoyl derivatives from methyl, or ethyl alcohol or methylated spirit, since these solvents will esterify the unchanged chloride and so remove the latter from the recrystalKsed material. Sometimes the benzoyl compound does not crystallise well this difficulty may frequently be overcome by the use of p-nitrobenzoyl chloride or 3 5-dinitro-benzoyl chloride, which usually give highly crystalline derivatives of high melting point (see Section IV, 114j. 

Examples of benzoylation under Schotten-Baumann conditions are — 

Benzanilide is more conveniently prepared, particularly on a larger scale, by heating together aniline and benzoic acid  

Benzoyl compounds are readily hydrolysed by heating with about 70 per cent, sulphuric acid (alkaline hydrolysis is very slow for anilides)  

In animals, methemoglobin formation is seen at concentrations above 10 ppm. Exposure of mice to 5000 ppm for 6-8 minutes was lethal, as was 2 500 ppm for 12 minutes cyanosis occurred after a few minutes, the red eye grounds became gray-blue, and then breathlessness appeared with paralysis and convulsions spectroscopy of the blood showed methemoglobin.  

Some recent studies in mice have suggested that concentrations of 2-10 ppm may reduce host resistance to infection.  

Nitric oxide is converted spontaneously in air to nitrogen dioxide hence, some of the latter gas is invariably present whenever nitric oxide is found in the air. At concentrations below 50 ppm, however, this reaction is slow and substantial concentrations of nitric oxide may occur with negligible quantities of nitrogen dioxide. It is likely that the effects of concomitant exposure to nitrogen dioxide will become manifest before the methemoglobin effects due to nitric oxide can occur. Nitrogen dioxide may cause irritation of the eyes, nose, and throat and delayed pulmonary edema.  

The 2003 ACGIH threshold limit valuetime-weighted average (TLV-TWA) for nitric oxide is 25ppm (31 mg/m ). 

Gustafsson LE Experimental studies on nitric oxide. Scand J Work Environ Health 19(Suppl 2) 44 8, 1993 

Submitted by Louts EHKt nkeld and Muton Pltterbauch. Checked by Roger Adams and S. V. Puntambeker. 

In a 3-I. round-bottom flask fitted with a reflux condenser are placed 218 g. (1 mole) of coarsely powdered technical o-nitro-aniline-/ -sulfonic acid, and a hot mixture of 775 cc. of concentrated sulfuric acid (sp. gr. 1.84) and 950 cc. of water (Note 1). Heat is applied and the mixture is refluxed gently for. an hour after solution is practically complete (total about three hours). The resulting dark solution is allowed to cool and is poured slowly into 12 1. of cold water in a crock (Note 2). 

The two crops of crystals may be combined for recrystallization from boiling water, using 11. for each 9 g. The hot solution 

If cold, diluted acid is used, stirring must be employed during the heating to prevent caking and consequent charring. 

The dark solution may be poured slowly over sufficient ice to half-fill a 16-I. (4-gal.) crock. A good yield was obtained in this way, but at this point the temperature is not likely to rise much and the use of cold water is cheaper and sufficiently satisfactory. 

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On acetylation it gives acetanilide. Nitrated with some decomposition to a mixture of 2-and 4-nitroanilines. It is basic and gives water-soluble salts with mineral acids. Heating aniline sulphate at 190 C gives sulphanilic add. When heated with alkyl chlorides or aliphatic alcohols mono- and di-alkyl derivatives are obtained, e.g. dimethylaniline. Treatment with trichloroethylene gives phenylglycine. With glycerol and sulphuric acid (Skraup s reaction) quinoline is obtained, while quinaldine can be prepared by the reaction between aniline, paraldehyde and hydrochloric acid. 

Similar difficulties arise in the nitrations of 2-chloro-4-nitroaniline and /)-nitroaniline. Consideration of the rate profiles and orientation of nitration ( 8.2.5) these compounds suggests that nitration involves the free bases. However, the concentrations of the latter are so small as to imply that if they are involved reaction between the amines and the nitronium ion must occur upon encounter that being so, the observed activation energies appear to be too high. The activation energy for the simple nitration of the free base in the case of/>-nitroaniline was calculated from the following equation ... 

An important reaction parameter is the choice of the base and NajCO or NaOAc have been shown to be preferable to EtjN in some systems[2]. The inclusion of NH4CI has also been found to speed reaction[2]. An optimization of the cyclization of A -allyl-2-benzyloxy-6-bromo-4-nitroaniline which achieved a 96% yield found EtjN to be the preferred base[3]. The use of acetyl or inethanesulfonyl as N-protecting groups is sometimes advantageous (see Entries 4 and 5, Table 4.1). 

AMNES - AMINES, AROMATIC - ANILINE AND ITS DERIVATIVES] (Vol 2) 4-Nitroaniline [100-01-6]... 

Indazole-2- N has been prepared from 2-methyl-4-nitroaniline and sodium nitrite- N,... 

An azo coupling reaction of monatomic phenols with diazotized 4-nitroaniline has been investigated. By HPLC, NMR, elemental analysis, UV and IR spectroscopy it has been shown that the azo derivatives of o-guaiacol, o- and m-cresols interact with an excess of diazonium in pH interval of 4,5-9,5 and form corresponding 4,4-di(4-nitrophenylazo)-2,5-cyclohexadien-1 -ones. 

An azo coupling reaction of primary aromatic and aliphatic amines with diazotized 4-nitroaniline in water-organic solutions has been investigated. It has been demonstrated that depending on the nature of an organic solvent different azo derivatives are formed in neutral medium. 

Dichloro-4-nitroaniline [99-30-9] M 207.0, m 193°. Crystd from aq EtOH or benzene/EtOH. 

Chlorosalicylic acid 2-Chloro-4-nitroaniline Phosphorus trichloride... 

It is prepd by the action of methylamine on 4-chloro-l-nitrobenzene (Ref 5) by the action of methyl iodide (Ref 6), or methyl sulfate on 4-nit roaniline (Ref 7) or by the hydrolysis of 4-nitro-N-methylformanilide with hot coned aq HC1 (Ref 8). In a study of the effect of nitric acid concn on the prods of the nitration of N,N-dimethylaniline to form Tetryl, it was isolated in low yield by the action of nitric acid, d 1.046g/cc, plus Na nitrite on N,N-dimethylaniline (Ref 10). A eutectic mixt with N-ethyl-4-nitroaniline has been patented as a stabilizer for NC (Ref 12). Studies at NPF indicate that 4-nitro-N-methyl-aniline is superior to Centralite, 2-nitrodiphenyl-amine, or Acardite in stabilizing. NC Refs 1) Beil 12, 586, (295) 1125 ... 

N,4-DinitrO N-methylaniline, bright yellow needles from benz, mp 142.5° (Ref 2) CA Registry No 16698-03-6. It is prepu by the alkylation of N,p-dinitroaniline with methyl iodide in alk soln (Refs 8 9). It is one compd isolated from aged NC propints stabilized with N-methyl-p-nitroaniline. Hollingsworth at ERDE examined the reaction of nitrogen dioxide with this stabilizer in order to elucidate the mechanism of the formation of the compds isolated. He found that after 7 days at 35°,. a good yield of N,4-dinitro-N-methylaniline was obtd and postulated that it arose from the oxidn of N-nitroso-4-nitroaniline (Ref 16)... 

Nitrophenylnitramine. Pale yel needles, mp 110—111°, explds on rapid heating. Can be prepd by nitrating 4-nitroaniline as above. Forms salts, some of which are expl... 

An increased hydrogen ion concentration, that is a considerably greater amount of acid than the theoretical two equivalents of Scheme 2-1, is necessary in the diazotization of weakly basic amines. The classic example of this is the preparation of 4-nitrobenzenediazonium ions 4-nitroaniline is dissolved in hot 5-10 m HC1 to convert it into the anilinium ion and the solution is either cooled quickly or poured onto ice. In this way the anilinium chloride is precipitated before hydrolysis to the base can occur. On immediate addition of nitrite, smooth diazotization can be obtained. The diazonium salt solution formed should be practically clear and should not become cloudy on standing in the dark. Some practice is necessary, and details can be found in the books emphasizing preparative aspects (Fierz-David and Blangey, 1952 Saunders and Allen, 1985 in Houben-Weyl, Vol. E 16a, Part II, the chapter written by Engel, 1990). These books give a series of detailed prescriptions for specific examples and a useful review of the principal variations of the methods of diazotization. Such reviews have also been written by Putter (1965) and Schank (1975). 

The rate-determining step in the diazotization of aniline in aqueous perchloric acid below concentrations of 0.05 m (pH >0.7) is the formation of N203. The following A-nitrosation step is faster (rate equation of Scheme 3-12). However, with aromatic amines that are weaker nucleophiles than aniline, e.g. 4-nitroaniline, nitrosation is slower than the formation of N203, and the rate is second-order with respect to nitrous acid and first-order in amine (Scheme 3-13, Larkworthy, 1959). 

Hartshorn and Ridd48 have also measured the variation of rate coefficient with acidity for nitration of 4-nitroaniline and 2-chloro-4-nitroaniline (Table 8). 

Ar NHi = Sulphanilic acid ArH = l-Naphthylamlne-4-sulphonic acid Aniline l-Naphthylamine-8-sulphonic acid 4-Nitroaniline Indole ... 

The removal of iodine from 2-iodo-4-nitroaniline in refluxing hydrochloric acid (ca. 100 °C), had a first-order rate coefficient of 4.7 x 10"5, and for 2-iodo-... 

Later, Taft and his coworkers examined the H-bonding donor ability of the amino protons in 4-nitroaniline and 4-nitrophenol as the hydrogen bond donors. They also tried... 

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