Acetanilide, hydrolysis nitration

Dinitw4 etbyl l metbyl benzener CH CcH CaHB(NOa)3 mw 210.20, N13.33% yel crysts, mp 48.5° Prepd from 5-ethyl 2 methyl-acetanilide by nitration at -1Q8-mp 177-8°, hydrolysis to the aniline-mp 186° followed by diazotization/removal of the amino group... 

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

Treating aniline with acetic anhydride, or refluxing together aniline with glacial acetic acid, yields acetanilide (21). Nitration with mixed acids affords p-nitroacetanilide hydrolysis of the acetyl group gives p-nitroaniiine (15b). 

Mono-substitution products of primary amines cannot easUy be prepared by direct action of the appropriate reagent for example, bromination of aniline yields largely the 2 4 6-tribomo derivative and nitration results in much oxidation. If, however, the amino group is protected as in acetanilide, smooth substitution occurs. Thus with bromine, />-bromoacetanilide is the main product the small quantity of the ortlio isomeride simultaneously formed can be easily eliminated by crystallisation. Hydrolysis of p-bromoacetanilide gives/ -bromoaniline ... 

Protection of the amino group by acetylation, as in acetanilide, therefore usually permits monosubstitution reactions with appropriate electrophilic reagents to proceed smoothly. Thus with bromine, p-bromoacetanilide is the main product the small quantity of the ortho isomer simultaneously formed can be easily eliminated by recrystallisation (Expt 6.67) hydrolysis of p-bromoacetanilide gives p-bromoaniline. Nitration leads similarly to p-nitroacetanilide which can be hydrolysed to p-nitroaniline (Expt 6.68). 

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. 

Preparation of diazoketones and their rearrangements during hydrolysis (method 271) and alcoholysis (method 295) are discussed elsewhere. Ammonolysis of diazoketones leads to amides of acids containing one more carbon atom than the original acyl halide. Halogen atoms may be present in a remote position on an aliphatic chain. The reaction is carried out by heating the diazoketone in alcohol or dioxane solution with aqueous ammonia in the presence of silver oxide or silver nitrate catalysts. Substituted acetanilides are formed when aniline is used in place of ammonia. ... 

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. 

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. 

The highly active amino function present in aniline is duly protected by acetylating it with acetic anhydride to obtain acetanilide and the elimination of a mole of acetic acid. The acetanilide is now subjected to nitration by concentrated sulphuric acid and fuming nitric acid to obtain the two products, namely para-nitro acetanilide ( 90%) and ortho-miro acetanilide ( 10%). Finally, the para-nitroaniline is obtained by carrying out the hydrolysis of the corresponding p-nitro acetanilide with 70% sulphuric acid. 

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. 

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