Phenylglutaric anhydride

The acrylonitrile should be distilled before use. Acrylonitrile vapors are toxic, and the distillation as well as the subsequent reaction should be carried out in a hood. 

This compound has not been described in the literature previously. The method of preparation follows the general method described by Bruson 2 for the cyanoethylation of arylacetonitriles. 

In a 500-ml. flask equipped with a reflux condenser are placed 48.4 g. (0.20 mole) of a-phenyl-a-carbethoxyglutaronitrile,1 225 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 1-1. separatory funnel, and diluted with 300 ml. of water. The a-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—18S°/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%. 

The extraction may be facilitated by saturation of the aqueous layer with sodium chloride. 

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These results may be compared with those of the experiments of Schwartz and Carter (64) and Cohen (65a) with fl-phenylglutaric anhydride. [See also the more recent results of Fujita and co-workers with meso-2,4-dimethylglutaric acid (65b).] The former group showed that a chiral amine could discriminate between attack at the pro-(/J) and pro-(S) carbonyl groups of the anhydride. The two diastereomers were formed in a ratio of 3 2, with optical purities of about 20%. 

Phenylacetylene, 72 /ra X-TPHENYL-l,3-BUTAniENE, 75 a-PHENYL-a-CARBETHOXYGLUTARO-NITRILE, 80, 82 0-Phenylenediamine, 56, 86 a-Phenylglutaric acid, 82 a-PHENYLGLUTARIC ANHYDRIDE, 81 Phenylhydrazine, 90 Phenylmagnesium bromide, 97 Phenylsuccinic acid, 83 Phenylsuccinic anhydride, 85 Phosphoric acid, ortho-, 33, 34 Phosphoric anhydride, 33 Phosphorus oxychloride, Tl Phosphorus pentoxide, 22, 46 Potassium, 19, 20 directions for safe handling of, 20 Potassium lerl.-butoxide, solution of, 19... 

The compound /3-phenylglutaric anhydride, 49, contains enantiotopic ligands. On reaction with ( —)-a-phenylethylamine the two diastereoisomers of the monoamide, 50 and 51, were formed in unequal amounts [67]. In contrast to the earlier statement (the products are usually enantiomers in an enantiodifferentiating process), the products here are diastereoisomers. Of course, if the amine component of the amide were to be removed, the products from the substrate anhydride would be enantiomers. This differentiation between enantiotopic groups was important in the early days of the citrate story. It proved the possibility of differentiation in homogeneous solution, presumably without a three-point attachment. 

P-Phenetidine hydrochloride, 31, 11 N-Phenylacetimidochloride, 31, 51 Phenylacetonitrile, 30, 44 Phenylacetylene, 30, 72 7-Phenylallylsuccinic acid, 31, 85 7-Phen ylallylsucci nic anhydride, 31, 86 Phenylazide, 31, 16 lrans-1 -Phenyl-1,3-butadiene, 30, 75 a-PHENYL-a-CARBETHOXYGLUTARO-nitrile, 30, 80, 82 Phenyldichlorophosphine, 31, 88 o-Phenylenediamine, 30, 56, 86 Qf-Phenylglutaric acid, 30, 82 a-PHENYLGLUTARIC ANHYDRIDE, 30, 81 Phenyl glycidyl ether, 31, 3 Phenylhydrazine, 30, 90 Phenylisocyanate, 31, 69 Phenylmagnesium bromide, 30, 97 31, 86... 

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