Acetanilide, nitration preparation

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. 

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 ... 

A freshly prepared solution of nitroguanidine in sulphuric acid contains no free nitric acid, but in the presence of substances which are readily nitrated it behaves as if this were so, e.g. the solution nitrates phenol, acetanilide and cinnamic acid and in the presence of mercury reacts in a nitrometer with the evolution of nitric oxide in the same way as nitric acid. Hence in certain cases a solution of nitroguanidine in sulphuric acid may be utilized as a nitrating mixture. 

Davis and Abrams [184a] have observed that aromatic compounds easy to nitrate such as phenol, acetanilide, etc. can be nitrated by a freshly prepared solution of nitroguanidine in sulphuric acid. 

In the meantime a mixture of one volume of 50 per cent aqueous potassium hydroxide, 4 volumes of water, and one volume of alcohol is prepared, cooled to o°, and the nitration product thoroughly rubbed up (in portions) in a chilled mortar with about 600 cc. of the solution. The o-nitro-acetanilide dissolves, while the bora- compound remains insoluble in the cold mixture and is sucked off and washed with a little of the cold... 

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. ... 

Several types of Schmidt reaction merit special mention (a) An interesting consequence of the factors governing migratory aptitudes is that acetanilides are the major (typically >95%) products of rearrangement of acetophenones. This leads to a practical alternative to nitration and reduction as a preparative route to aromatic amines , cf. reaction (24). (b) Product analyses showed that... 

For the preparation of o-nitroaniline the method outlined above may be used. Nitration at a temperature of 40° is employed so as to increase the proportion of the o-nitroacetanilide to 25 per cent. Another variation is to treat aniline with excess of acetic anhydride and then with nitric acid. Acetanilide is first formed, which in the presence of acetic anhydride nitrates to give a larger proportion of the ortho isomer. The nitrating agent is assumed to be acetyl nitrate, CHaCOONOs. Finally, a number of indirect methods are... 

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