Submitted by A. W. Ingersoll
Checked by Reynold C. Fuson and William E. Ross.
1. Procedure
In a
500-cc. modified Claisen flask are placed
250 g. (4 moles) of ammonium formate (Note
1),
150 g. (1.25 moles) of acetophenone (Note
2), and a few chips of porous plate. The flask is fitted with a
cork carrying a thermometer extending nearly to the bottom, and the side arm is connected to a
small condenser set for distillation. On heating the flask with a small flame the mixture first melts to two layers and distillation occurs; at 150–155° it becomes homogeneous and reaction takes place with moderate foaming. The heating is continued, more slowly if necessary, until the temperature reaches 185°. During this process water,
acetophenone, and
ammonium carbonate distil; about three hours is required and little attention is necessary. At 185° the heating is stopped and the upper layer of
acetophenone is separated from the distillate and returned, without drying, to the reaction flask. The mixture is then heated for three hours at 180–185°. The distillate is extracted with
25–30 cc. of benzene to recover
acetophenone (Note
3), and the aqueous portion is discarded.
The reaction mixture is cooled and then shaken in a
500-cc. separatory funnel with 150–200 cc. of water to remove
ammonium formate and
formamide. The crude
α-phenylethylformamide is drawn off into the original flask, and the water layer is extracted with two
30-cc. portions of benzene and discarded. The
benzene extracts are united with the main portion, and
150 cc. of concentrated hydrochloric acid is added, together with a few pieces of porous plate. The mixture is cautiously heated until the
benzene has distilled and then boiled gently for forty to fifty minutes longer. Hydrolysis proceeds rapidly, and the mixture becomes homogeneous except for a small layer of
acetophenone and other neutral substances. The mixture is cooled and extracted first with
50 cc. of benzene and then with three or four 25-cc. portions of the solvent. The extracts are saved for the recovery of
acetophenone (Note
3).
The aqueous acid solution is transferred to a
1-l. round-bottomed flask provided with a separatory funnel and equipped for steam distillation. A solution of
125 g. of sodium hydroxide in 250 cc. of water is added through the funnel, and the mixture is distilled with steam (Note
4). The first liter of distillate contains most of the amine, but the distillate should be collected until it is only faintly alkaline. A small residue containing
di-(α-phenylethyl)-amine and neutral substances remains in the flask and may be discarded.
The distillate is extracted with five
50-cc. portions of benzene, and the
benzene solution is dried thoroughly with powdered
sodium hydroxide and distilled (Note
5). Most of the amine distils at 184–186°, but the fraction distilling at
180–190° is sufficiently pure for most purposes (Note
6). The yield of this fraction is
80–88 g. By combining the
benzene fore-run with the distillation residue, extracting with dilute acid, and recovering the amine as above, an additional
10–12 g. of material can be obtained (Note
7), making the total yield
90–100 g. (
60–66 per cent of the theoretical amount based on the
acetophenone taken) (Note
8).
2. Notes
1.
Ammonium formate may be made in quantity by treating solid
ammonium carbonate with a slight excess of commercial
85 per cent formic acid and concentrating the solution, in stages, on a
steam bath under reduced pressure. The slightly moist product obtained by suction filtration is suitable for this preparation.
3. The
benzene solution is washed with dilute alkali, dried, and distilled, the fraction boiling at
198–207° being collected.
4. In the steam distillation it is advisable to heat the distillation flask directly so that the volume remains nearly constant.
5. The amine attacks cork and rubber and absorbs
carbon dioxide from the air. It is best distilled in a flask having an in-set side arm and collected in a distilling flask protected by a
soda-lime tube.
6. If very pure amine is desired the product described above is dissolved with 1.04 parts of crystalline
oxalic acid in 8 parts of hot water. After clarification with
Norite, the filtered solution on cooling deposits crystals of the acid oxalate. About 5 g. of the salt remains in each 100 cc. of the mother liquor; most of this can be obtained by evaporation and further crystallization. The amine is liberated from the pure oxalate with
potassium hydroxide, distilled with steam, and purified as described above. When a known amount of amine is desired in water solution (as for optical resolution), a weighed amount of the (anhydrous)
oxalate is decomposed and the amine is distilled quantitatively with steam.
7. When several runs are to be made the acid solution of the amine may be combined with the next run previous to steam distillation.
3. Discussion
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