From Nitroanilines

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. 

Arenediazonium hexafluoroantimonates were described as early as 1935,275 but their fluorodediazoniation was only studied much later.276 They deliver fluoroaromatics in better yields than other diazonium salts only when electron-withdrawing groups (N02, C02H) are present on the ring. Otherwise, antimony(V) fluoride formed in the reaction acts as a strong Lewis acid and catalyzes the formation of byproducts. The phenomenon is more pronounced with diazonium hexafluoroarsenates which deliver fluoro compounds in acceptable yields only from nitroanilines.276 With unsubstituted or electron-releasing substituted anilines, difluo-rinated arenearsonic acids are often the major product. 

Amino-6-nitrobenzothiazole as a sodium flux inhibitor (anticonvulsant activity) has been synthesized from nitroaniline via a one-pot procedure (Scheme 2.104) [587],... 

Dinitrobenzene has been prepared from -nitrosonitro-benzene by treatment with nitric acid from />-nitroaniline by the Sandmeyer reaction and by the oxidation of />-nitroaniline in concentrated sulfuric add with ammonium persulfate. ... 

Nilro derivatives of 2,5,H-triphcnyl-tris-triazoloben7ene (XI) are very inteicsi ing heat resistant compounds (52). The substances were obtained by couplin. diazoti/ed nitroaiiilines with 1.3.5-triamim)benzene. followed by oxidation wiili ( uSOa. Compounds from >-nitroaniline and 2.4-dinitroaniline had m.ps ol 370 C and 4 )0°( respectively. 

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

In addition to the enamine 369 described in Scheme 2.69, the other four enamines 372-375 obtained from nitroanilines 359 and diphenylacetaldehyde 253o, cyclohexanecarboxaldehyde 253p, fran -cinnamaldehyde 253q, and 1,3-cyclohexanedione 376 were examined (Scheme 2.70) (Wallace et al. 2008). The condensation of aldehydes 253o-q and 1,3-cyclohexanedione 376 with nitroanilines 359 resulted in enamines 372-375 in 91, 88, 85, and 70 % isolated yields, respectively. The A-heteroannulation of 372-375 similarly gave the quinoxaline derivatives 377, 378, 379, 380, 382 in 69, 70, 13, 25, and 26 % isolated yields. In addition to fully aromatic quinoxaline 195, the corresponding A-oxide 381 was obtained, albeit in lower yields in the case of mono-phenyl substituted enamine 374. 

Scheme 2.69 Palladium-catalyzed synthesis of quinoxaline derivatives 370, 371 starting from nitroanilines and 2-methylpropanal 253b...

Concentrate each of the two solutions (or eluates) to about 20 ml, by distilling off the greater part of the benzene, the distilling-flask being immersed in the boiling water-bath. Then pour the concentrated solution into an evaporating-basin, and evaporate the remaining benzene (preferably in a fume-cupboard) in the absence of free flames, i.e., on an electrically heated water-bath, or on a steam-bath directly connected to a steam-pipe. Wash the dry residue from the first eluate with petrol and then dry it in a desiccator pure o-nitroaniline, m.p. 72°, is obtained. Wash the second residue similarly with a small quantity of benzene and dry pure />--nitroaniline, m.p. 148" , is obtained. Record the yield and m.p. of each component. 

Heat a mixture of 15 g. of p-nitroacetanilide 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 500 ml. of cold water and precipitate the p-nitroanihne 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-nitroanihne, m.p, 148°, is 11 g. 

Add 101 g. (55 ml.) of concentrated sulphuric acid cautiously to 75 ml. of water contained in a 1 htre beaker, and introduce 35 g. of finely-powdered wi-nitroaniline (Section IV,44). Add 100-150 g. of finely-crushed ice and stir until the m-nitroaniUne has been converted into the sulphate and a homogeneous paste results. Cool to 0-5° by immersion of the beaker in a freezing mixture, stir mechanically, and add a cold solution of 18 g. of sodium nitrite in 40 ml. of water over a period of 10 minutes until a permanent colour is immediately given to potassium iodide - starch paper do not allow the temperature to rise above 5-7° during the diazotisation. Continue the stirring for 5-10 minutes and allow to stand for 5 minutes some m-nitrophenjddiazonium sulphate may separate. Decant the supernatant Uquid from the solid as far as possible. 

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

Dissolve 10 g. of p-nitroaniline (Section IV,51) in a mixture of 21 ml. of concentrated hydrochloric acid and an equal volume of water, and cool rapidly to 0° in order to obtain the hydrochloride of the base in a fine state of division. Diazotise in the usual way (see Section IV,68) by the gradual addition of a solution of 6 0 g. of sodium nitrite in 12 ml. of water. Continue the stirring for a few minutes, filter the solution rapidly, and add it from a separatory funnel to an ice-cold solution of 41 g. of sodium sulphite (90 per cent. NajS03,7H20) in 100 ml. of water containing... 

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. 

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. 

Benzenesulphonyl chloride reacts with primary and secondary, but not with tertiary, amines to yield substituted sulphonamides (for full discussion, see Section IV,100,3). The substituted sulphonamide formed from a primary amine dissolves in the alkaline medium, whilst that produced from a secondary amine is insoluble in alkali tertiary amines do not react. Upon acidifying the solution produced with a primary amine, the substituted sulphonamide is precipitated. The reactions form the basis of the Hinsberg procedure for the separation of amines see Section IV,100,(viii) for details. Feebly basic amines, such as o-nitroaniline, react slowly in the presence of allcali in such cases it is best to carry out the reaction in pyridine solution see Section IV,100,3. ... 

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 ... 

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. 

Dye formation is complex because shading is achieved by employing several developers and several couplers in the same dye bath. The process is illustrated by -phenylenediamine, which is oxidized by the peroxide to a quinone diimine. This short-Hved intermediate can react, for example, with resorcinol to yield a brownish indoaniline. Table 17 provides some insight into the many interactions that exist from just a few components. Further shading is possible by including semipermanent colorants (see Table 16), especially nitroaniline derivatives. 

Quinoxaline mono-N-oxides are also available by a direct synthesis from n-nitroaniline derivatives. Condensation of acetyl chloride derivatives with o-nitroaniline followed by treatment with sodium ethoxide in ethanol yields the mono-N-oxides in good yields (Scheme 20) (64JCS2666). 

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