A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1950, 30, 83
DOI: 10.15227/orgsyn.030.0083
[Succinic acid, phenyl-]
Submitted by C. F. H. Allen and H. B. Johnson1.
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°.
7. The checkers found the product at this stage to be of sufficient purity for conversion to phenylsuccinic anhydride.
3. Discussion
Preparative methods for phenylsuccinic acid have been listed in an earlier volume.4 More recent procedures have been based on the hydrolysis of ethyl α-phenyl-β-cyanopropionate,5 tetraethyl 1-phenyl-1,1,2,2-ethanetetracarboxylate,6 diethyl (α-phenyl-β-nitroethyl) malonate,7 and ethyl8 or methyl 2,3-dicyano-3-phenylpropionate.9
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

References and Notes
  1. Eastman Kodak Co., Rochester, New York.
  2. Org. Syntheses Coll. Vol. 3, 377 (1955).
  3. Org. Syntheses Coll. Vol. 2, 4 (1943).
  4. Org. Syntheses Coll. Vol. 1, 451 (1941).
  5. Wideqvist, Arkiv Kemi, Mineral. Geol., 26A, No. 16 (1948) [C. A., 43, 2167 (1949)].
  6. Hsing and Li, J. Am. Chem. Soc., 71, 774 (1949).
  7. Perekalin and Sopova, Zhur. Obshchei Khim., 24, 513 (1954) [C. A., 49, 6180 (1955)].
  8. Sen and Bagchi, J. Org. Chem., 20, 845 (1955).
  9. Miller and Long, J. Am. Chem. Soc., 73, 4895 (1951).
  10. Bredt and Kallen, Ann., 293, 344 (1896).
  11. Verkade and Hartman, Rec. trav. chim., 52, 945 (1933).
  12. Wideqvist, Arkiv Kemi, Mineral. Geol., 14B, No. 19, 6 pp. (1940) [C. A., 35, 3993 (1941)].

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

ethanol (64-17-5)

calcium chloride (10043-52-4)

hydrogen chloride,
hydrochloric acid (7647-01-0)

ether (60-29-7)

hydrogen cyanide (74-90-8)

potassium cyanide (151-50-8)

Norit (7782-42-5)

Phenylsuccinic acid,
Succinic acid, phenyl- (635-51-8)

diethyl benzalmalonate (5292-53-5)

potassium bicarbonate (298-14-6)

Ethyl β-phenyl-β-cyanopropionate (14025-83-3)

phenylsuccinic anhydride (1131-15-3)

ethyl α-phenyl-β-cyanopropionate

tetraethyl 1-phenyl-1,1,2,2-ethanetetracarboxylate

diethyl (α-phenyl-β-nitroethyl) malonate