4- acetamide

Acetamide [60-35-5] C2H NO, mol wt 59.07, is a white, odorless, hygroscopic soHd derived from acetic acid and ammonia. The stable crystalline habit is trigonal the metastable is orthorhombic. The melt is a solvent for organic substances it is used ia electrochemistry and organic synthesis. Pure acetamide has a bitter taste. Unknown impurities, possibly derived from acetonitrile, cause its mousy odor (1). It is found ia coal mine waste dumps (2). 

Most commercial routes for the production of acetamide involve dehydration of ammonium acetate [631 -31 -8]  

Industrial production is often based on transformation of this laboratory method into a continuous process (10). Another route is acetonitrile [75-05-8] hydration  

Because huge quantities of by-product acetonitrile are generated by ammoxidation of propylene, the nitrile may be a low cost raw material for acetamide production. Copper-cataly2ed hydration gives conversions up to 83% (11), and certain bacteria can effect the same reaction at near room temperature (12). 

Acetamide has been used experimentally as a source of nonprotein nitrogen for sheep and dairy cattie (13). It does not appear to be toxic in amounts of about 2—3% of ration. Buffering the diet with dibasic acids serves to allow higher levels of intake because the ammonia Hberated in the digestive process is then scavenged. 

The intermediate products, which are represented within brackets, are exceptionally labile since they contain OH and the negative acetoxyl group attached to the same carbon atom (cf. p. 103) they therefore decompose into two molecules of acid or, in the case of ammonia, into acetic acid and acetamide. The reaction with alcohols is to be formulated in the same way. It will be observed that, when an acyl group is introduced (into an alcohol, amine, etc.) by means of an anhydride, one of the two acid radicles in the molecule is always converted into the acid and is consequently not used in the acylation. The great reactivity of the acid chlorides has the same cause as that discussed in connexion with the anhydrides. 

2 Finely powdered ammonium carbonate is added to 60 c.c. of glacial acetic acid at 40°-50° until a sample of the solution, after dilution with water, reacts alkaline. It must be remembered that in this process 0-5 mole of water is formed per mole of ammonium acetate. 

Amides are prepared, quite generally, from the acids by subjecting the ammonium salts to dry distillation, or still better, by beating them for a long time at a high temperature. 

Formerly acetamide was usually prepared by heating ammonium acetate to 200° in a sealed tube. By this method, however, the reaction cannot proceed to completion because the water set free in the reaction partly hydrolyses the amide again  

as in the process given, the water formed is removed from the reaction mixture by distillation, the back reaction is restricted and the yield increased. At the same time the excess of acetic acid counteracts the dissociation of the salt which takes place according to the equa- 

Kane LE, Dombroske R, Alaire Y Evaluation of sensory irritation from some common industrial solvents. Am Ind Hyg Assoc J 41 451-455, 1980 

Egle JL Jr Effects of inhaled acetaldehyde and propionaldehyde on blood pressure and heart rate. ToxicolApplPharmacol23-Ah - 35, 1972 

Kruysse A, Eeron VJ, Til EIP Repeated exposure to acetaldehyde vapor. Studies in Syrian golden hamsters. Arch Environ Health 30 449-152, 1975 

lARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol 71, Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide, pp 319-335. Lyon, International Agency for Research on Cancer, 1999 

Eeron VJ, Kruysse A, Woutersen RA Respiratory tract tumors in hamsters exposed to acetaldehyde vapor alone or simultaneously to benzo( )pyrene or diethylni-trosamine. EurJ Cancer Clin Oncol 18 13-31, 1982 

Ammonium carbonate of commerce is often extremely impure, and care must be taken to obtain a representative sample for the determination of the ammonia content by titration with standard acid. The ammonium carbonate used in this preparation contained 27.2 per cent of ammonia, and 1470 g. was used in each run. 

As acetamide is somewhat hygroscopic, it cannot be exposed to the air unless precautions are taken to have the air dry. 

The foregoing process is based on the method of W. A. Noyes and W. F. Goebel,9 in which equimolecular proportions of ammonium acetate and acetic acid are heated together, the acetic acid having been shown to accelerate both the dehydration of ammonium acetate and the hydrolysis of acetamide. 

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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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