Nitroanilines nitration

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. 

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. 

Many aromatic compounds are sufficiently basic to be appreciably protonated in concentrated sulphuric acid. If nitration occurs substantially through the free base, then the reactivity of the conjugate acid will be negligible. Therefore, increasii the acidity of the medium will, by depleting the concentration of the free base, reduce the rateof reaction. This probably accounts for the particularly marked fall in rate which occurs in the nitration of anthraquinone, benzoic acid, benzenesulphonic acid, and some nitroanilines (see table 2.4). 

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 ... 

At lower acidities the observed rate constant for nitration of p-nitroaniline becomes greater than that for nitration of anilinium. ... 

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). 

A neat synthesis of 4-nitroindole depends on an acyladon-deacyladon sequence from 2-methyl-3-nitroaniline, as shown in Eq. 10.53. On the other hand, treatment of iV-protected indoles v/ith acetyl nitrate generated in sini at bw temperanire gives the correspondmg... 

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 ... 

Nitroaminocompounds or Nitroamines. Compds containing both —N02 and —NH2 radicals attached to different C atoms, eg, nitroaniline, 02N.C6H4.NH2, etc. Nitroamines can be prepd either by the nitration of amines, or by partial reduction of nitrocompounds contg several —N02 groups. Another method is to treat a chloronitrocompound with ammonia, as in the prepn of dinitroaniiine... 

Metafor 3- Mononitrophenol Monoclinic prisms from eth or dil HC1 mp 97° bp 194° at 70mm, decomps when distd at ordinary pressure d 1.485g/cc at 20°, 1.2797 at 100°. Does not volatilize with steam cannot be prepd by the nitration of phenol. Can be obtained by boiling diazotized m-nitroaniline with w and sulfuric acid (Ref 3). SI sol in w, sol in ale. Highly toxic by ingestion and inhalation Refs 1) Beil 6, 222-24, (116), [212-14]... 

Nitrophenylnitramine. O2N.CfiH4.NH.NO2, mw 183.12,N 22.95%, OB to C02 -91.2%, pale yel needles or brownish yel plates, mp 65.5°, explds on rapid heating. Can be obtained by nitrating 2-nitroaniline with nitric acid and Ac20. Forms salts, some of which are expl... 

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). 

The results obtained using this criterion are very close to reality. Two of the compounds that are known to be unstable and appear in this series, ie nitroaniline and ammonium nitrate, which have an expiosophoric group without necessarily being noted for being explosive, are classified medium risk . There are still two anomalies the far too severe classification for 1,2-dichiorobenzene, which is obviously due to the endothermic nature of the aromatic cycle Crt would be better to analyse 1,2-dichlorocyclohexane using the technique mentioned before) and on the other hand, the underestimated risk of ammonium dichromate, which is, incidentally, overestimated in the regulations as will be seen later. 

When analysing the resulte it is noticed this time that criterion C4 is the least severe of the four CHETAH criteria. It emphasises the unstable property of nitroaniline but under mates the instability of ammonium nitrate and ammonium dichromate for which there is no indication of danger whatsoever. 

It is noted that 2-nitroaniline and ammonium nitrate are the two compounds that give the most consistent results. These are the two most unstable compounds of this series. All authors who showed some interest in this approach ruled out the possibility of looking for a unique criterion which would synthesise these four approaches, a point of view not shared by the present author. 

First, it is thought that the CHETAH approach generally overestimates instability risk. Indeed, if these compounds are analysed, they are all, apart from nitroaniline and ammonium nitrate, known as not being dangerous but they are all mentioned as medium risk at least once. 

So fares nitroaniline is concerned, the absence of an estimate in the regulations does not seem wise as the entries on nitrated derivatives in Chapter 6 will demonstrate. 

Finally, there are a few reactions of nitroanilines which involve the amine group and for which the danger is entirely or partly related to the presence of nitrated functional groups. 

When o-Nitroaniline is treated by sodium nitrite in acid medium and then by an inorganic sulphide, it forms an explosive diazonium sulphide. Note that even though the presence of a nitrated group does not help, it certainly is not a factor that is vital to cause the explosion, since this is a property that is common to all these diazonium salts whatever the nature of the substitution on the ring. The situation is exactly the same with p-nitroaniline. 

Nitration leads similarly to -nitroacetanillde, which can be hydrolysed to p-nitroaniline ... 

Nitroaniline Nitric acid, Sulfuric acid, 2314 Nitronium perchlorate, 1,2-Epoxides, 4028 2.2 -Oxybis(ethyl nitrate), 3260 Sodium nitrate, Phenol, Trifluoroacetic acid, 4721 See also NITRATING AGENTS... 

Nitration of m-nitroaniline (28) with fuming nitric acid and oleum yields 2,3,4,6-tetranitroaniline (29), a powerful but chemically unstable explosive. 2,3,4,6-Tetranitroaniline readily reacts with a range of nucleophiles, including water to yield 3-amino-2,4,6-trinitrophenol. 

Ridd and Yoshida explored the At-nitration of aromatic nitroanilines with nitronium hex-afluorophosphate in nitromethane with the aim of studying the Bamberger rearrangement (Chapter 4, Section 4.5). In was found that amines of low basicity essentially undergo complete A -substitution if the amine is in excess 2,4-dinitroaniline and 2,3-dinitroaniline form A, 2,4-trinitroaniline and At,2,3-trinitroaniline, respectively, as the sole products. More basic nitroanilines give mixtures of C-substituted, At-substituted and poly-substimted materials. The use of nitronium salts for At-nitration has been extensively reviewed. ... 

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