Acetamidation

J-Pyran-2-acetamid, Ai-[[6-(2,3-dimethoxypropyl)tetrahydro-4-hydroxy-5,5-dimethyl-2H-pyran-2-yl]rriethoxymethyl]tetrahydro-a-hydroxy-2-methoxy-5,6-dimethyl-4-rTiethylene]-... 

Naphthalene, oxalic acid (hydrated), cinnamic acid, acetamide, benzamide, m-dinitrobenzene,/>-nitrophenol, toluene p-sulphon-... 

Dehydration of the corresponding ammonium salt. Thus ammonium acetate on heating loses water giving acetamide. An excess of acetic acid is... 

CH,CO O OCCH, + H NH, CH,CONH, + CH,COOH Acetic anhydride Acetamide... 

Acetamide is thus obtained as a colourless crystalline solid, which has a characteristic odour of mice, stated to be due to the presence of small quantities of methylacetamide, CH3CONHCH3. The acetamide can be purified and rendered odourless by re-crystallisation from acetone, and then has m.p. 82°, b.p. 223°. If this recrystallisation is contemplated, the distilled material should be collected directly into a small weighed beaker or conical flask, so that the solidified acetamide can be readily broken up and removed. 

The crude acetonitrile contains as impurity chiefly acetic acid, arising from the action of phosphoric acid on the acetamide. Therefore add to the nitrile about half its volume of water, and then add powdered dry potassium carbonate until the well-shaken mixture is saturated. The potassium carbonate neutralises any acetic acid present, and at the same time salts out the otherwise water-soluble nitrile as a separate upper layer. Allow to stand for 20 minutes with further occasional shaking. Now decant the mixed liquids into a separating-funnel, run off the lower carbonate layer as completely as possible, and then pour off the acetonitrile into a 25 ml, distilling-flask into which about 3-4 g. of phosphorus pentoxide have been placed immediately before. Fit a thermometer and water-condenser to the flask and distil the acetonitrile slowly, collecting the fraction of b.p. 79-82°. Yield 9 5 g. (12 ml.). 

Acetonitrile is a colourless liquid, of b.p. 82° and [Pg.122]

A certain amount of hydrolysis of the original acetamide to acid and ammonia always occurs, and the final amine always contains traces of ammonia. This is separated by extracting the mixed anhydrous hydrochlorides with absolute ethanol, which dissolves the amine hydrochloride but not the ammonium chloride filtration of the hot ethanolic extract removes the ammonium chloride, whilst the amine hydrochloride crystallises readily from the filtrate on cooling. 

Dissolve 36 g. of sodium hydroxide in 160 ml. of water contained in a 500 ml. conical flask, and chill the stirred solution to 0-5° in ice-water. Now add io-8 ml. (32-4 g.) of bromine slowly to the stirred solution exercise care in manipulating liquid bromine ) during this addition the temperature rises slightly, and it should again be reduced to 0-5°. Add a solution of 12 g. of acetamide in 20 ml. of water, in small portions, to the stirred hypobromite solution so that the temperature of the mixture does not exceed 20° the sodium acet-bromoamide is thus obtained in the alkaline solution. Now remove the flask from the ice-water, and set it aside at room temperature for 30 minutes. 

B) Formamide, acetamide, oxamide, urea, benzamide, salicylamide thiourea. 

Acetamide CH3CONH2 Urea H3NCONH2 Glycine HgNCHjCOOH Amino-carboxylic... 

Ammonium acetate CH3COONH4 Acetamide CH CONHj Acetonitrile CH CN Phthalimide C,H,(CO),NU Acetanilide C H,NHCOCH,... 

Amides themselves (e,g., acetamide) also often respond to the reaction ... 

D) Nitriles. Acetonitrile, CH3CN, b.p. 82°, is miscible with water, but benzonitrile, CaHjCN, b.p. 191, is insoluble. Acetonitrile, unless specially purified, retains the mouse like odour of acetamide benzonitrile has an odour resembling both that of benzaldchyde and of nitrobenzene (bitter almonds). 

Solutions of solids in liquids can sometimes be separated by distilling off the liquid and leaving a residue of the solid, e.g., acetone and acetamide. 

Acetamide and acetonitrile, unless specially purified, possess a mouse-like odour. 

An excess of acetic acid is usually added before heating in order to repress the hydrolysis (and also the thermal dissociation) of the ammonium acetate, thus preventing the escape of ammonia. The excess of acetic acid, together with the water, is removed by slow fractional distillation. The method is rarely used except for the preparation of acetamide. 

Acetic acid Urea Acetamide Carbamic Acid... 

By the action of concentrate aqueous ammonia solution upon esters. This process is spoken of as ammonolysls of the ester, by analogy with hydrolysis applied to a similar reaction with water. If the amide is soluble in water, e.g., acetamide, it may be isolated by distillation, for example ... 

ACETAMIDE (from Ammonium Acetate or from Acetic Acid)... 

The acetamide often contains a minute amount of impurity having an odour resembling mice excrement this can be removed by washing with a small volume of a 10 per cent, solution of ethyl alcohol in ether or by recrystallLsation. Dissolve 5 g. of impure acetamide in a mixture of 5 ml. of benzene and 1 5 ml. of dry ethyl acetate warm on a water bath until all is dissolved and cool rapidly in ice or cold water. Filter oflF the crystals, press between Alter paper and dry in a desiccator. The unpleasant odour is absent and the pure acetamide melts at 81°. Beautiful large crystals may be obtained by dissolving the acetamide (5 g.) in warm methyl alcohol (4 ml.), adding ether (40 ml.) and allowing to stand. 

If the acetamide crystallises in the condenser, it may be melted by the cautious application of a flame. 

The student should carry out the following simple experiments with acetamide or with any other ahphatic amide, e.g., n-caproamide they illustrate some of the general reactions of primary ahphatic amides. 

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