Acetophenone, acidity

Liquids.—It may be a hydrocarbon (paraffin,olefine,aromatic) Jiiyher alcohol e.g. amyl alcohol), aldehyde [eg., benzaldehyde) ketone [eg., acetophenone) acid [e.g., valeric acid), ether, cdei, phenol [e.g., zveewtiCxaX) phenol ether [e.g, anisole). 

Through lack of an unambiguous method for direct determination, the acidity constants of carbon acids have, for many years, been estimated from the rate of proton abstraction by means of rate-equilibrium relationships. Thus, Bell (1943) (see also Hibbert, 1977) estimated the acetaldehyde, acetone and acetophenone acidity constants (19.7,20.0 and 19.2, respectively) by assuming that the rate constants for proton abstraction from several mono- and dicarbonyl compounds to a single base (A-) with pAHA = 4.0 obey a Bransted equation in its differential form (47). By taking curvature into account, the... 

Aldehydes and ketones may be converted into the corresponding primary amines by reduction of their oximes or hydrazones (p. 93). A method of more limited application, known as the Leuckart Reaction, consists of heating the carbonyl compound with ammonium formate, whereby the formyLamino derivative is formed, and can be readily hydrolysed by acids to the amine. Thus acetophenone gives the i-phenylethylformamide, which without isolation can be hydrolysed to i-phenylethylamine. 

Required Acetophenone, 30 g. ammonium formate, 50 g. benzene, 30 ml. hydrochloric acid, 30 ml. ether, 100 ml., sodium hydroxide. 

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids. 

The preparation of acetophenone (p. 255) is a modification of this method, the alkyl halide being replaced by an acid chloride, with the consequent formation of a ketone. 

The Fischer Indolisation Reaction occurs when the phenylhydrazone of a suitable aldehyde or ketone undergoes cyclisation with loss of ammonia, under the influence of various reagents, such as zinc chloride, ethnnolic hydrogen chloride, or acetic acid. For example, the phenylhydrazone of acetophenone (p. 257) when heated with zinc chloride gives 2 phenylindole. ... 

Then add 3 drops of acetophenone (or about 0 3 g. of powdered benzo-phenone dissolved in 1 ml. of acetic acid) and shake the mixture. A precipitate of the phenylhydrazone is produced on scratching. 

Almost insoluble in cold water. Higher alcohols (including benzyl alcohol), higher phenols (e.g., naphthols), metaformaldehyde, paraldehyde, aromatic aldehydes, higher ketones (including acetophenone), aromatic acids, most esters, ethers, oxamide and domatic amides, sulphonamides, aromatic imides, aromatic nitriles, aromatic acid anhydrides, aromatic acid chlorides, sulphonyl chlorides, starch, aromatic amines, anilides, tyrosine, cystine, nitrocompounds, uric acid, halogeno-hydrocarbons, hydrocarbons. 

The ketones are readily prepared, for example, acetophenone from benzene, acetyl chloride (or acetic anhydride) and aluminium chloride by the Friedel and Crafts reaction ethyl benzyl ketones by passing a mixture of phenylacetic acid and propionic acid over thoria at 450° and n-propyl- p-phenylethylketone by circulating a mixture of hydrocinnamic acid and n-butyric acid over thoria (for further details, see under Aromatic Ketones, Sections IV,136, IV,137 and IV,141). 

The reaction is illustrated by the conversion of 3 5-dinitrobenzoic acid into 3 5-dlnltroaniline, and of acetophenone into acetanilide ... 

Acetanilide from acetophenone. Dissolve 12 g. of acetophenone in 100 ml. of glacial acetic acid containing 10 g. of concentrated sulphuric acid. To the stirred solution at 60-70°, add 9 8 g. of sodium azide in small portions at such a rate that the temperature does not rise above 70°. Stir the mixture with gentle heating until the evolution of nitrogen subsides (2-3 hours) and then allow to stand overnight at room temperature. Pour the reaction mixture on to 300 g. of crushed ice, filter the solid product, wash it with water and dry at 100°. The yield of crude acetanilide, m.p. 111-112°, is 13 g. Recrystallisation from water raises the m.p. to 114°. 

When an alkyl aryl ketone is heated with yellow ammonium polysulphide solution at an elevated temperature, an aryl substituted aliphatic acid amide is foimed the product actually isolated is the amide of the ci-aryl carboxylic acid together with a smaller amount of the corresponding ammonium salt of the oarboxylio acid. Thus acetophenone affords phenylacetamide (50 per cent.) and ammonium phenylacetate (13 per cent.) ... 

For the nitration of the very weak base, acetophenone, there is reasonable agreement between observed and calculated activation parameters, and there is no doubt that nitration of the free base occurs at acidities below that of maximum rate. In this case the equilibrium concentration of free base is much greater than in the examples just discussed and there is no question of reaction upon encounter. ... 

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