Nitroanilines reactions

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. 

The hydrochloride of the nitroanilin may separate out at this stage, but this does not interfere with the reaction as the hydrochloride separates in fine, feathery crystals which readily redissolve and hence are very reactive. 

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 ... 

Some amines, such as the nitroanilines and the naphthylamines, give somewhat more stable diazonium compounds and may be diazotised at room temperature, when the reaction proceeds more rapidly. If the amine salt is only sparingly soluble in water, it should be suspended in the acid in a fine state of division (this is generally attained by cooling a hot solution and stirring vigorously), and it passes into solution as the soluble diazonium salt is formed. 

Feebly basic amines, e.g., the nitroanilines, generally react so slowly with benzenesulphonyl chloride that most of the acid chloride is hydrolysed by the aqueous alkali before a reasonable yield of the sulphonamide is produced indeed, o-nitroaniline gives little or no sulphonamide under the conditions of the Hinsberg test. Excellent results are obtained by carrying out the reaction in pyridine solution ... 

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. ... 

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 ... 

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). 

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. 

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. 

General Conditions for each step and selectivity of m-substituted anilines As previously mentioned, Hauser and Reynolds reported on factors governing the first step of the Conrad-Limpach reaction but they tvere by no means exhaustive. Other than the conditions reported above for the first step, HClAleOH, CHCI3 or CHCI2 (neat or with acid catalyst), PhMe or PhH with removal of water with or without acid catalyst, or EtOH/AcOH/CaS04 were reported to provide the desired enamino-ester from an aryl amine and 3-keto-ester. Hauser and Reynolds also noted that o-nitroaniline and o-nitro-p-methoxyaniline failed to form the desired enamino-ester under conditions which they reported. 

More importantly, Peet and coworkers reported the reaction of o-nitroaniline 35 with acetylene dicarboxylate 32 to provide fumarate 36. Subsequent cyclization proved difficult under thermal conditions and only a 35% yield of quinolone 37 was isolated. Use of PPA for the cyclization improved the yield of 37 significantly. Using this modification allowed enamino-ester formation with a nitro-group attached to the arylamine. 

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 reaction of 2-nitroanilines with cyanamide gives 3-amino-1,2,4-benzotiia-zine 1-oides 133 (88MI1, 94GEP4244009). 

The corresponding reaction with 2-methylamino-5-nitroaniline affords an unambiguous synthesis of l-methyl-6-nitroquinoxaIin-2-one, the A -mcthyl derivative of (6) this product is also obtained by treatment of (6) with methyl iodide and methanolic sodium methoxided ... 

An analogous sequence leads to the anthelmintic agent, etibendazole (50). Reaction of the benzophenone 47, which can be obtained by acylation of o-nitroaniline with g-fluorobenzoyl chloride, with ethylene glycol leads to acetal 48. Sequential reduction of the nitro group and cyclization of the resulting diamine (49) with N,N-dicarbomethoxy-S-methylthiourea gives the benzimidazole etibendazole (50) fl6]. 

From 13.1 g of N-preduction with Raney-nickel and hydrogen, in which reaction the substance may be suspended in methanol or dissolved in methanol-ethyl acetate at normal pressure and at about 40°C with combination of the theoretical quantity of hydrogen, 12.2 g are obtained of o-emino-N-pfrom aqueous methanol hasaMPof90°C. 

The NH2 groups can be diazotized and reduced in the presence of thiosulphates and different metal ions. The effect of some metal ions, namely Fe ", Sn, Cu +, and Co on the graft yield of cotton modified with aryl diazonium groups via its reaction with 2,4-dichloro-6-(p-nitroaniline)-5-triazine in the presence of alkali and followed by reduction of nitro group was studied [4]. 

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)... 

OB to C02 -54,3%, mp explds at approx 1S4°, hygr crysts. Prepd by dissolving m-nitroaniline in an excess of dil perchloric acid (d 1.12g/cc), the excess being such that, at the end of the reaction, free acid is present. A sufficient quantity nf Na nitrite in solid form or in a sstd soLp. is added to effect diazotization. The mixt is cooled during the Na nitrite addition ,... 

The so-called self-diazotization was developed by Sihlbohm (1951, 1953 a, 1953 b). It is based on the observation that several nitroaniline derivatives, on treatment with hydrochloric acid in acetic acid solution, form the corresponding chlorobenzenedi-azonium ions. 2,5-Dinitroaniline will serve as an example (Scheme 2-37). This reaction had already been discovered in principle by Meldola and Eyre in 1901. The method did not become important. 

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