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Org. Synth. 1950, 30, 81
DOI: 10.15227/orgsyn.030.0081
α-PHENYLGLUTARIC ANHYDRIDE
[Glutaric anhydride, 2-phenyl-]
Submitted by E. C. Horning and A. F. Finelli1.
Checked by William S. Johnson and H. Wynberg.
1. Procedure
In a 500-ml. flask equipped with a reflux condenser are placed 48.4 g. (0.20 mole) of α-phenyl-α-carbethoxyglutaronitrile (p. 776), 225 ml. of hydrochloric acid (sp. gr. 1.19), and 50 ml. of acetic acid. The mixture is heated under reflux for 10 hours. The solution is cooled, transferred to a 1-l. separatory funnel, and diluted with 300 ml. of water. The α-phenylglutaric acid is extracted with five 100-ml. portions of ether-ethyl acetate (1:1) (Note 1). The extracts are combined, washed once with saturated sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvents are removed as completely as possible by distillation from a steam bath, and the residue is transferred to a 200-ml. flask. Acetic anhydride (50 ml.) is added, and the solution is heated under gentle reflux for 1 hour. The excess acetic anhydride is removed by distillation at atmospheric pressure, and the residue is distilled under reduced pressure through a short (15-cm.) Vigreux column with an air-cooled side arm. The product is collected at 178–188°/0.5–1 mm. (Note 2). The yield is 31.1–32.7 g. (82–86%); m.p. 90–94°.
This material may be recrystallized by dissolving the product in hot ethyl acetate (2 ml. per g. of the anhydride) and adding an equal volume of hexane or 60–68° petroleum ether slowly to the hot solution. The solution is allowed to cool, and when crystallization occurs (usually at 40–50°) an additional volume (2 ml. per g. of the anhydride) of hexane is added. The mixture is cooled, and the crystalline product is removed by filtration and washed with cold hexane (5 ml. per g. of the anhydride). The recovery of colorless material, m.p. 95–96°, is 90–92%.
2. Notes
1. The extraction may be facilitated by saturation of the aqueous layer with sodium chloride.
2. It is necessary to flame the column and side arm. The product obtained in this way is a light-yellow or cream-colored solid which need not be recrystallized unless a colorless sample is desired. If the final distillation is carried out too slowly or at pressures above 2 mm. considerable decomposition may occur, reducing the yield of the product.
3. Discussion
α-Phenylglutaric acid has been prepared by the hydrolysis and decarboxylation of diethyl α-phenyl-α-carbethoxyglutarate (prepared by the alkylation of diethyl phenylmalonate with ethyl β-iodopropionate) with hydrochloric acid.2 The anhydride may be obtained from the acid by direct distillation under reduced pressure, although the use of acetic anhydride results in a purer product.

References and Notes
  1. University of Pennsylvania, Philadelphia, Pennsylvania.
  2. Fichter and Merckens, Ber., 34, 4175 (1901).

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

petroleum ether

hydrochloric acid (7647-01-0)

acetic acid (64-19-7)

ethyl acetate (141-78-6)

ether (60-29-7)

acetic anhydride (108-24-7)

sodium chloride (7647-14-5)

magnesium sulfate (7487-88-9)

diethyl phenylmalonate (83-13-6)

hexane (110-54-3)

α-Phenyl-α-carbethoxyglutaronitrile (53555-70-7)

α-Phenylglutaric anhydride,
Glutaric anhydride, 2-phenyl- (2959-96-8)

α-phenylglutaric acid

diethyl α-phenyl-α-carbethoxyglutarate

ethyl β-iodopropionate (6414-69-3)