Nitroanilines, preparation

Chromatographic Separation of a Mixture of o- and p-Nitroaniline. Prepare a glass tube A (Fig. 24) in which the wider portion has a diameter of 3 cm. and a length of ca. 30 cm. the narrow portion at the base has a diameter of 5-7 mm. Wash the tube thoroughly (if necessary, with chromic acid, followed by distilled water and ethanol) and then dry. Insert a small plug of cotton-wool P as shown just within the narrow neck of the tube it is essential that this plug does not project into the wider portion of the tube. Clamp the tube in a vertical position. 

Hydrolysis of the Salts of the Nitroanilines.—Prepare a sample of aniline hydrochloride as follows Mix together 1 cc. of aniline and 1 cc. of concentrated hydrochloric acid. Cool under running water, and place the solid which separates on a porous plate. When the liquid has been absorbed pour a little ether on the salt. Repeat the treatment with ether, and let the salt dry in the air. Prepare samples of the hydrochlorides of meta- and para-nitroanilines as follows Mix together about 1 gram of the amine with 5 cc. of concentrated hydrochloric acid and 5 cc. of water. Heat to boiling, and then cool in running water. Filter the salt by suction, and wash the crystals with 10 cc. of alcohol and then with 10 cc. of ether. Dry the salts for a few minutes on filter-paper. 

Dichloro-6-nitroaniline. Prepared by method of Witt, by chlorination of 4-chloro-2-nitroaniline. Recrystallized from alcohol and acetone. Melting point 101.1°. 

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. 

CgHgNa. While crystals m.p. 147 C, b.p. 267"C, darken rapidly in air. Prepared by reducing p-nitroaniline or aminoazobenzene. Oxidizing agents convert it to quinone derivatives, hence it cannot be diazotized with nitric acid. 

Z>) Benzoylation. Proceed exactly as for benzoylation of amines (Test 3 (a), p.374), but use a suspension of the finely ground nitroaniline in the 10% NaOH solution. This preparation of the benzoyl derivatives is rarely necessary, however, as the above acetylation proceeds very satisfactorily. (M.ps., p. 550.)... 

It is convenient to include under Aromatic Amines the preparation of m-nitroaniline as an example of the selective reduction of one group in a polynitro compound. When wt-dinitrobenzene is allowed to react with sodium polysulphide (or ammonium sulphide) solution, only one of the nitro groups is reduced and m-nitroanUine results. Some sulphur separates, but the main reaction is represented by ... 

Prepare the diazoniuni fluoborate from 34 g. of p-nitroaniline as detailed in Section IV,68 for o-Nitroaniline. 

Compounds containing two primary amino groups attached to a benzene ring can be prepared by the reduction of dinitro compounds and of nitroanilines, usually with tin or stannous chloride and hydrochloric acid or with iron and very dilute hydrochloric acid. / ara-diamines may also be obtained by the reduction of aromatic amino-azo compounds (e.g., p-aminodimethylanihne from methyl orange, see Section IV,78). p-Phenylenediamine may also be prepared from p-nitroacetanilide reduction with iron and acid yields p-amino-acetaniUde,.which may be hydrolysed to the diamine. 

Experimental details are given for o-phenylenedlamlne, which is conveniently prepared by the reduction of o-nitroaniline in alcoholic sodium hydroxide solution with zinc powder ... 

Phenol may be nitrated with dilute nitric acid to 3deld a mixture of o- and nitrophenols the 3deld of p-nitrophenol is increased if a mixture of sodium nitiute and dilute sulphuric acid is employed. Upon steam distilling the mixture, the ortho isomer passes over in a substantially pure form the para isomer remains in the distillation flask, and can be readily isolated by extraction with hot 2 per cent, hydrochloric acid. The preparation of m-nitrophenol from wt-nitroaniline by means of the diazo reaction is described in Section IV,70. 

Most derivatives of aniline are not obtained from aniline itself, but ate prepared by hydrogenation of their nitroaromatic precursors. The exceptions, for example, /V-a1ky1ani1ines, /V-ary1ani1ines, sulfonated anilines, or the A/-acyl derivatives, can be prepared from aniline and have been discussed. Nitroanilines are usually prepared by ammonolysis of the corresponding chloronitroben2ene. Special isolation methods may be requited for some derivatives if the boiling points are close and separation by distillation is not feasible. Table 6 Hsts some of the derivatives of aniline that are produced commercially. 

Perhaps one of the most exciting developments in the chemistry of quinoxalines and phenazines in recent years originates from the American University of Beirut in Lebanon, where Haddadin and Issidorides first made the observation that benzofuroxans undergo reaction with a variety of alkenic substrates to produce quinoxaline di-AT-oxides in a one-pot reaction which has subsequently become known as the Beirut reaction . Many new reactions tend to fall by the wayside by virtue of the fact that they are experimentally complex or require starting materials which are inaccessible however, in this instance the experimental conditions are straightforward and the starting benzofuroxans are conveniently prepared by hypochlorite oxidation of the corresponding o-nitroanilines or by pyrolysis of o-nitrophenyl azides. 

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

Nitrophenyl isocyanate has been prepared by heating -nitrophenyl carbamyl chloride. The latter has been obtained by the action of phosgene on -nitroaniline in benzene-toluene solutions, and by the action of phosphorus pentachloride on methyl jii-nitrophenylcarbamate. The preparation given above is based upon recent publications of the authors. ... 

Diaminoazobenzene was reported by Nietzki to have been prepared by diazotizing -nitroaniline and coupling the product with aniline. The resulting 4-nitrodiazoaminobenzene is rearranged and the nitro group reduced. The submitters tried several times to carry out this procedure but were unsuccessful. 4,4 -Diaminoazobenzene has been prepared by the oxidation of -nitroaniline with potassium persulfate followed by the reduction of the nitro groups. ... 

Each of the following compounds has been prepared from p-nitroaniline. Outline a reasonable series of steps leading to each one. 

Kemp utilized a very similar oxo-diester 49. Not only was this ketone reactive enough to form an enamine using p-nitroaniline 48, but 49 underwent bis-addition of aniline 48, providing 50 in 64% yield. Intermediate 50 smoothly cyclized to provide quinolone 51 which was utilized to prepare a diacylaminoepindolidione, a template to study the folding of 3-pleated sheets. 

Early attempts to prepare 5-amino- and 5-acylaminobenzofuroxans by hypochlorite oxidation of the corresponding o-nitroanilines met with failure. Pyrolysis of the appropriate azide, however, gives 5-dimetliylamino- and 5-acetamidobenzofuroxan, whereas urethans of type (33) are produced by Curtius degradation of the 5-carboxylic acid. Controlled hydrolysis of the acetamido compound and the... 

Thiazolo[5,4-/i]quinoline 22 was prepared 2 years later starting from 4-ami-nobenzothiazole, also by the Skraup procedure. The 4-aminobenzothiazole was prepared in six steps from 2-nitroaniline (40HCA328) (Scheme 11). 

The same methodology was also used starting from the ethyl 6-amino-7-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate, prepared by reduction of the nitro derivative. The requisite nitro derivative was prepared by nitration of ethyl 7-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate. A second isomer was prepared from 4-chloro-3-nitroaniline by reaction with diethyl ethoxymethylene-malonate, subsequent thermal cyclization, and further ethylation because of low solubility of the formed quinolone. After separation and reduction, the ethyl 7-amino-6-chloro-l-ethyl-4-oxo-l,4-dihydroquinoline-3-carboxylate 32 was obtained. The ort/io-chloroaminoquinolones 32,33 were cyclized to the corresponding 2-substituted thiazoloquinolines 34 and 35, and the latter were derivatized (Scheme 19) (74JAP(K)4, 79CPB1). 

The w-nitroaniline may also be added to the mixture prepared by adding the ice to the diluted acid, but this procedure is not quite so satisfactory. 

TV-Alkylbenzene-1,2-diamines, prepared by catalytic hydrogenation of ACalkyl-2-nitroanilines, form benzotriazepine-2,4-diiiiiines 4 with sodium dicyanimide.377... 

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). 

FIGURE 3 Release of -nitroaniline and the degradation of PCPA versus time. Disks (1.4 cm in diameter and 1 mm thick) of poly-(carboxyphenoxyacetic acid) (PCPA) were prepared containing 5% (w/w) -nitroaniline by compression molding, and degraded in 0.1 M pH 7.4 phosphate buffer at 37°C. The cumulative release of p-nitroaniline and degradation of PCPA were measured by absorbance at 380 and 235 nm, respectively. 

Compression-molded devices of poly(N-palmitoyl hydroxyproline ester) (side chain length 16 carbons), poly(N-decanoylhydroxy-proline ester) (side chain length 10 carbons), and poly(JN-hexanoyl-hydrox roline ester) (side chain length 6 carbons) were prepared with dye contents of 1,5,10, and 20% of either -nitroaniline or acid orange. Release curves were obtained by placing the loaded devices into phospate buffer (pH 7.4) at 37 C. The amount of released dye was followed spectrophotometrically in the usual fashion. 

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