Nitration: of acetanilide

TABLE 5.6 Proportions of isomers formed in the nitration of acetanilide ... 

Nitration. Direct nitration of aromatic amines with nitric acid is not a satisfactory method, because the amino group is susceptible to oxidation. The amino group can be protected by acetylation, and the acetylamino derivative is then used in the nitration step. Nitration of acetanilide in sulfuric acid yields the 4-nitro compound that is hydroly2ed to -rutroaruline [100-01-6]. 

Note nitration of acetanilide has been discussed in the following refs ... 

Data have been presented on the kinetics of nitration of acetanilide in mixtures of nitric and sulfuric acids.29 A review discusses the several mechanisms operative in the nitration of phenol including /> / -sclective nitrosation-oxidation and mechanisms involving phenoxy radical-nitrogen dioxide reaction yielding a 55 45 ortho para nitration ratio.30 The kinetics of mononitration of biphenyl-2-carboxylic acid have been investigated in several solvents. The maximum ortho para product ratio of 8.4 is observed in tetrachloromethane.31 Nitration products were not formed in the presence of dioxane.31,32 Quantum-chemical AMI calculations were performed and the predominant formation of the ortho-nitro product is accounted for by stabilization of the cr-complex by the carboxyl group.33... 

This was observed in the nitration of acetanilide (Holleman, Hertogs and van der Linden [53] Amall [70]), propionanilide (Amall [70]), anisol (Griffiths, Wal-key and Watson [71] Halverson and Melander [72]). The effect was much less pronounced when toluene was nitrated (Holleman, Vermeulen and de Mooy [54]). 

Khmer [2] found that acetanilide when nitrated also yields o- nitroacetanilide, from which o- nitroaniline may be obtained by hydrolysis. The nitration of acetanilide... 

Dinitroaniline forms yellow needles, difficult to dissolve in cold alcohol. The compound was obtained by Rudnev [8] by vigorous nitration of acetanilide to 2,4-dinitroacetanilide with an almost anhydrous nitrating agent, followed by hydrolysis of the product. 

Nitration of acetanilide. Add 25 g (0.185 mol) of finely powdered, dry acetanilide to 25 ml of glacial acetic acid contained in a 500-ml beaker introduce into the well-stirred mixture 92 g (50 ml) of concentrated sulphuric acid. The mixture becomes warm and a clear solution results. Surround the beaker with a freezing mixture of ice and salt, and stir the solution mechanically. Support a separatory funnel, containing a cold mixture of 15.5 g (11ml) of concentrated nitric acid and 12.5 g (7 ml) of concentrated sulphuric acid, over the beaker. When the temperature of the solution falls to 0-2 °C, run in the acid mixture gradually while the temperature is maintained below 10 °C. After all the mixed acid has been added, remove the beaker from the freezing mixture, and allow it to stand at room temperature for 1 hour. Pour the reaction mixture on to 250 g of crushed ice (or into 500 ml of cold water), whereby the crude nitroacetanilide is at once precipitated. Allow to stand for 15 minutes, filter with suction on a Buchner funnel, wash it thoroughly with cold water until free from acids (test the wash water) and drain well (1). Recrystallise the pale yellow product from ethanol or industrial spirit, filter at the pump, wash with a little cold alcohol and dry in the air upon filter paper (2). (The yellow o-nitroacetanilide remains in the filtrate.) The yield of p-nitroacetanilide, a colourless crystalline solid of m.p. 214 °C, is... 

Although protonation of the amine leads to the anilinium salt which is a deactivating substituent, nitration of aniline in nitric acid sulfuric acid yields 60% para and 34% meta substitution, whilst nitration of acetanilide gives 79% para and 19% ortho nitroacetanilides. 

Explain the following observations, (a) Nitration of acetanilide gives mainly 4-nitroacetanilide and nitration of 2-... 

Nitroanilines are employed extensively in dye manufacture. Amination of o-chloronitro-benzene, at 175 °C and 40 atmospheres, affords o-nitroaniline. Partial reduction of m-dinitrobenzene gives the corresponding meta-derivative. The para-isomer 15b is used more extensively than the other nitroanilines in dye manufacture. In addition to amination of p-chloronitrobenzene, it can be made by nitration of acetanilide to yield (21), followed by hydrolysis. 

Nitration of acetanilide yields a mixture of ortho and para substitution products. The para isomer is separated, then subjected to hydrolysis to give p-nitroaniline. 

The nitration of acetanilide with mixed acid yields nitroacetanilides in which the ortho para ratio is less than 0.1. When the nitration medium is nitric acid, this ratio is 0.7, when acetyl nitrate in acetic anhydride is used, the product is almost entirely o-nitroacetanilide. No satisfactory explanation has been given for these results. The 40-50 per cent yield of m-nitro-aniline that results from the nitration of aniline in mixed acid or in nitric acid can be explained in the following manner. In the strong acids, nitric and sulfuric acid, aniline is largely ionized. 

In the nitration of acetanilide, it is important, in order to prevent hydrolysis, to conduct the nitration at 3-5 C. To ensure a maximum yield of product, use is made of cycle acid, which in this instance is water-white 66 B sulfuric acid. Into 4,000 lb of sulfuric acid that is free of nitrous acid 1,000 lb of dry acetanilide (mp, 113 C) is delivered very slowly- During the 3-4 hr that are consumed in this operation, the temperature is maintained at 25 C. The charge is cooled to 2 C, and 1,450 lb of mixed acid of the following composition is then slowly run into the nitrator, the rate of feed being regulated by the capacity of the brine coils to control the temperature at 3-5°C. 

Nitration of acetanilide gives />-nitroacetanilide in excellent yield with only a trace of the ortho isomer. Acidic hydrolysis of />-nitroacetanilide (Section 18.8F) removes the acetyl group and gives y>-nitroaniline, also in good yield. 

Ortho-selective nitration of acetanilides with nitrogen dioxide in the presence of ozone, at low temperatures results in ortho-nitro derivatives formation in high yields [98]. 

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