Organic Syntheses, CV 4, 804
Submitted by C. F. H. Allen and H. B. Johnson
1.
Checked by H. R. Snyder, D. J. Mann, and Leonard E. Miller.
1. Procedure
Caution! This preparation should be conducted in a
well-ventilated hood to avoid exposure to
hydrogen cyanide.
A.
Ethyl β-phenyl-β-cyanopropionate. In a
5-l. round-bottomed three-necked flask suspended in an
oil bath and fitted with a
mechanical stirrer, a
reflux condenser, and a
250-ml. dropping funnel is placed a solution of
200 g. (0.81 mole) of diethyl benzalmalonate2 in
2 l. of absolute ethanol. The stirrer is started, and a solution of
56 g. (0.86 mole) of potassium cyanide in 100 ml. of water is added rapidly from the
separatory funnel; a small amount of the
potassium cyanide precipitates. The temperature of the oil bath is raised to 70° and maintained at 65–75° for 18 hours.
The mixture is cooled to 15°, and the precipitated
potassium bicarbonate is collected on a
Büchner funnel. The solid (weight 70–72 g.) is washed on the funnel with
100 ml. of 95% ethanol. The combined filtrate and wash liquor is transferred to a 5-l. round-bottomed flask and made slightly acid
(Caution! (Note 1)) with dilute
hydrochloric acid (about 15–20 ml. of the 10% acid is required). The solution is then concentrated under reduced pressure to a semi-solid residue (Note
1). The cooled residue is shaken with a mixture of 300 ml. of water and
500 ml. of ether. The material dissolves completely; the water layer is separated and washed with
200 ml. of ether. The
ether solutions are combined, dried over
20 g. of calcium chloride, filtered into a
2-l. round-bottomed flask equipped with a glass joint, and concentrated by distillation (heating on a
steam bath). The crude
ethyl β-phenyl-β-cyanopropionate remains as a clear red oil weighing
130–140 g. It is sufficiently pure for use in the next step (Note
2).
B.
Phenylsuccinic acid. To the crude ester obtained above is added
500 ml. of concentrated hydrochloric acid (sp. gr. 1.19). The flask is fitted to a condenser (Note
3), and the mixture is heated under reflux for 18 hours (Note
4). At the end of this time only a small amount of red oil remains (Note
5). The mixture is cooled, and the nearly solid cake which forms is broken up and collected on a glass filter cloth (Note
5). The crude tan-colored
phenylsuccinic acid is washed with 300 ml. of cold water and dried at 60°. It then weighs
105–110 g. (
67–70%) and melts at
163–164° (Note
6) and (Note
7).
2. Notes
1. Since
hydrogen cyanide may be liberated during the acidification and the subsequent concentration, both operations should be carried out in a well-ventilated hood.
2. The pure ester can be obtained by distillation under reduced pressure (b.p.
161–164°/8 mm.).
3. Glass-jointed equipment is required in this step. The flask with a glass joint was used in the preceding operation only to avoid the necessity of transferring the product after the evaporation.
4.
Hydrogen chloride is evolved during the first part of the refluxing; it may be disposed of by absorption in water in a
gas trap.
3
5. The red, oily impurity usually distributes itself as a film on the surface of the liquid and as a lump at the bottom of the flask. It solidifies on cooling and is most conveniently removed as a solid; the thin crust on the surface is lifted with a
spatula, and the lump at the bottom of the flask is left undisturbed when the product is collected on the filter.
6. The pure acid can be obtained by recrystallization from water. For each 10 g. of acid about 300 ml. of water and
0.5 g. of Norit are required. The recovery is
85–90% of pure white acid melting at
165.5–166°.
3. Discussion
The procedure given above is more economical of time and materials than that previously published.
4 Applications of the present method, due originally to Bredt and Kallen,
10 have been published.
11,12
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