ON THE PREPARATION OF ACETAMIDE.* By M. A. ROSANoff, louise GULICK, and H. K. LARKIN.

1. Methods Used Hitherto.

ACETAMIDE has long been prepared by the action of aqueous ammonia upon ethyl acetate, as originally proposed by Dumas, Malaguti, and Leblanc (Comptes Rendus, 1847, xxv., 657). The reaction mixture has no effect upon iron, and so the process can be carried out on a considerable

scale in iron autoclaves.

The preparation of amides from the ammonium salts of the corresponding acids was first introduced by Dumas (Ann. Chim. Phys., 1830, [2], xliv., 142). The details of this method, as now generally employed for the preparation of acetamide on a laboratory scale, were worked out by Hofmann (Berichte, 1882, xv., 977). Hofmann sums up the condition of the preparative method at the time he undertook its amelioration in the following words : -

"If, however, the preparation of amides by treating esters with ammonia leaves much to be desired, the yields obtained by the distillation of ammonium salts are even less satisfactory. Experiments on the preparation of acetamide by this method have been published by Kündig (Ann. Chem. Pharm., 1858, cv., 277), who obtained, in the most favourable case, using glacial acetic acid saturated with ammonia gas, something over 25 per cent of the theoretical yield. In all these distillations streams of ammonia escape at first, which naturally reduces the yield of amide. Petersen (Ann. Chem. Pharm., 1858, cvii., 331), who, at Bunsen's suggestion, modified the experiment by distilling a mixture of equivalent quantities of fused sodium acetate and sal ammoniac, states that acetamide may thus be easily and advantageously prepared, but says nothing concerning the percentage yield. When this experiment was repeated perfectly pure acetamide was obtained directly, but in this case too a large quantity of ammonia was lost, and the final yield of acetamide amounted to only 20 per cent of theory."

Hofmann's method, as given in its optimum form by Gattermann ("Practical Methods of Organic Chemistry," trans. by Schober, New York, 1907), consists in neutralising 75 grms. of acetic acid with ammonium carbonate and heating in sealed tubes for five hours at 225°. The reaction product is subjected to fractional distillation; the fraction passing over between 180° and 230° is collected separately, and on solidification pressed out on a drying-plate. The pressed out crystals are re-distilled, yielding about 40 grms. of almost pure acetamide.

This operation, however, cannot be carried out on a

⚫ Contribution from the Chemical Laboratories of Clark University, Worcester, Mass.

large scale. We quote from Hofmann (loc. cit., p. 981): -"Unfortunately this operation cannot be carried out, like the treatment of esters with ammonia, in iron autoclaves, as these are strongly attacked. Acetamide will, therefore, be best prepared in the future, as heretofore, by treating the ester with ammonia at ordinary temperatures." One or two modifications of the Hofmann method have been proposed since 1882. Schultze (Journ. Prakt. Chem., 1883, xxvii., 512) warms ammonium acetate with acetic anhydride, using no less than 130 grms. of anhydride to 100 grms. of the acetate. This, however, is not only costly, but unquestionably yields much diacetamide together with acetamide. Keller (Fourn. Prakt. Chem., 1885, xxxi., 364) distils ammonium acetate in a current of ammonia. We have tried out this method, but with no satisfactory results; unless one carries out a great many re-distillations, which is disproportionately laborious, the yield is very small (generally about 12 per cent of theory).

2. New Method. Hofmann's method has two disadvantages:-First, the acetate must be heated in sealed vessels; secondly, iron vessels cannot be employed.

From the view-point of chemical statics, there is very little advantage in raising the temperature to 220°. According to Menschutkin (Journ. Prakt. Chem., 1884, xxix., 445) the maximum percentages of acetamide formed at different temperatures are as follows:

Obviously, almost as much acetamide could be obtained at 140° as at 220°. The reason that the higher temperature is generally employed is that at lower temperatures the reaction is impracticably slow.

method simple and convenient by employing a suitable This suggested the possibility of rendering the old catalytic agent.

The most appropriate catalyst, apparently, was suggested by the following simple considerations. From the fact that the hydrolysis of amides is catalysed by acids, the inference was drawn that acids would also hasten the oppo

site reaction, i.e., amide formation. Mineral acids could not be used as they would take up the ammonia from the ammonium acetate. Organic acids generally would yield their own amides in addition to acetamide. Acetic acid alone could do no harm, and might be confidently expected to promote the reaction catalytically.

Experiment soon showed that in the presence of an excess of acetic acid the amide formation really took place with considerable velocity in open vessels. It remained to determine the essential details of the preparation, and this required a large number of trials. The following directions will be found to yield satisfactory results.

First, good dry ammonium acetate is prepared by neutralising glacial acetic acid with pulverised ammonium carbonate at about 50°, allowing to cool, draining off the crystals, and pressing them out twice or three times with filter-paper. The product so obtained contains very nearly 98 per cent of the pure salt.

(NOTE. The use of ammonium acetate freed from water is best for the obvious reason that water promotes hydrolysis of the amide, and hence necessarily diminishes the yield. Commercial ammonium acetate contains more or less free acid and is unreliable, unless neutralised and pressed out afresh).

100 grms. of this ammonium acetate (corresponding to 75 grms. of acetic acid) and 113 grms. glacial acetic acid (ratio: 1 mol. acetate to 15 mols. acid) are boiled in a one-litre flask, with reflux condenser, for five hours. The product is rapidly distilled over with minimum loss and subjected to fractionation (again out of a one-litre flask) with the aid of a two-bulb Wurtz stillhead. (This distillation materially improves the yield). This operation should be carried out as slowly as possible. Three fractions are collected separately: (1) the fraction passing over below 180°; (2) the fraction passing over between 180° and 2130; (3) the fraction passing over above 213°. During the distilling of fraction 3 the stillhead is unnecessary. The second fraction (180-213°) is slowly re-distilled with the Wurtz stillhead, and the portion passing over above 213° is added to fraction 3, the remainder being added to fraction I. The original product is thus divided into a low-boiling and a high-boiling fraction. The former may again be neutralised with ammonium carbonate, and the resulting salt used for a new preparation. The high-boiling fraction, on thorough solidification, is twice pressed out with filter-paper. The dry crystals (practically pure acetamide) weigh over 60 grms., or 20 grms. more than the product obtained by the use of sealed tubes according to the Hofmann-Gattermann directions. The yield is, how. ever, slightly variable, depending on the quality of the ammonium acetate used and especially on the care with which the fractionation is carried out.

(NOTE.-In two consecutive preparations carefully carried out in this Laboratory by Mr. H. R. Godfrey, the yields were respectively 62 grms. and 63.5 grms. At the suggestion of Prof. William A. Noyes, Mr. Godfrey was also requested to try the preparation of acetamide from ammonia and an excess of acetic acid directly, without isolating the ammonium acetate). Dry ammonia gas was introduced into 188 grms. Kahlbaum's glacial acetic acid (=75 grms. +113 grms. excess, as above) until the increase in weight amounted to 213 grms. This was changed to acetamide according to our directions. Two such consecutive trials yielded respectively 633 grms. and 622 grms. acetamide. The simplification will be valuable when only one preparation is to be carried out).

It is obvious that the above directions permit of transforming ammonium acetate into acetamide on as large a scale as may be desired, and ought to lead to a considerable reduction of the present price of acetamide, and in order to make certain that the low temperature employed did not after all materially diminish the yield, some experiments were carried out on the following plan:-100 grms. of our fairly dry ammonium acetate and 113 grms. of acetic acid were heated for three hours (experiments

about 56 grms. There is certainly no advantage in using sealed tubes.

Our product boils at 214-216°, which shows it to be nearly pure acetamide.

Clark University, Worcester, Mass.,
March, 1911.

REEDER (CHEMICAL NEWS, xcvi., 199) gives analysis of the fruit of Solanum dulcamara. His results were mainly qualitative, so it occurred to us it might be profitable to make a more quantitative study of the fruit of this interesting species.

The Solanum dulcamara, or woody night-shade, a native of Europe, was introduced into the United States soon after the discovery of America. The flowers of this plant resemble the potato, but are smaller. The fruit is a red ovate berry, and, on account of its luscious appearance, is often eaten by accident.

The berry is quite sweet owing to the large content of sugars. When burned, it gives off three distinct odours; first, an odour similar to that of boiling molasses; secondly, an odour resembling burnt sugar; lastly, an odour of burning wood. The fruit is easily crushed in an agate

mortar.

There were 304 grms. of berries available for the analysis, which were obtained in August, 1906, at Sylvan Beach, New York. The average weight of a berry was 125 grm. The Sugars.

200 grms. of the fruit were used in the sugar extraction. They were placed in a litre flask, fitted with an inverted condenser, and were treated with boiling alcohol for 250 hours. Each day the alcohol was removed and a fresh portion supplied. The alcoholic extract was distilled off, leaving a thick syrup in the flask.

The process was continued for thirty days; at the end of this time the extract failed to reduce Fehling's solution. The colour of the alcoholic extract was a deep wine colour, but at the end of thirty days the extract was almost colourless, and distilled water was substituted for the alcohol. The berries had remained firm, but soon became mushy under the water treatment. The water extract did not show a clear wine colour, but was black and muddy. Fourteen days more were required to remove all colouration and the remainder of the sugars.

The percentage of the sugars was determined by the reduction of Fehling's solution. The solution was standardised, and it was found that 10 cc. were completely reduced by o'05 grm. of sugar. 15 cc. of the litre solution of the alcoholic sugar extract was added to 50 cc. of boiling water, and titrated with the Fehling's solution. The end-point of the reaction was determined by filtering a small portion from time to time, and pouring the filtrate back until the sugars had no more reducing power. The filtrate was a straw colour until the end-point was reached, when it became a bright blue. The change in colour could be brought about either way by the addition of three drops of Fehling's solution or the same of the sugar solution, so the test appeared to be satisfactory. The water extract was determined in exactly the same manner. There were found to be 610 grms. of sugar in the alcoholic extract and 105 in the water extract. As 200 grms. of berries were used in the extractions, the above weights correspond to 31.55 per cent of sugar.

The two portions were evaporated to dryness, and the odour resembled burnt sugar. The residue was black and gummy, having the sweetish taste of the original berry.