Glutaric Acid and Glutarimide

Submitted by G. Paris, L. Berlinguet, and R. Gaudry.1 Checked by James Cason and Edwin R. Harris. 

In a 500-ml. three-necked flask fitted with a sealed mechanical stirrer and a reflux condenser are placed 86 g. (1 mole) of 7-butyrolactone (Note 1) and 72 g. (1.1 moles) of potassium cyanide (Note 2). As the contents of the flask are stirred, the mixture is heated in an oil bath for 2 hours at a temperature of 190-195° (Note 3). There is an initial vigorous reaction which soon subsides. After the completion of the heating period the mixture is cooled to about 100°, and the potassium salt of the cyano acid is dissolved in about 200 ml. of hot water. The warm solution is cautiously acidified to Congo Red by the addition of about 90 ml. of concentrated hydrochloric acid. The resultant solution, which contains glutaric acid monoamide and potassium chloride, is used to prepare glutaric acid or glutarimide. 

Glutaric Acid. To the solution of monoamide is added 200 ml. of concentrated hydrochloric acid, and the mixture is heated under reflux in the hood for 1 hour. The reaction mixture is evaporated to 

If a pure grade of glutaric acid is desired, it is decolorized by boiling for about 1 hour with 10 g. of charcoal in water solution. The charcoal is removed by filtration (Note 4), the water is evaporated under reduced pressure, and the dry residue is recrystallized from chloroform. The yield of white glutaric acid, m.p. 98-99°, is 94-99 g. (71-75%). 

Butyrolactone from Eastern Chemical Corporation, 34 Spring Street, Newark 2, New Jersey, was used without purification. 

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Glutarimide has been prepared from glutaric acid and sulfamide 3 or formamide,4 by distillation of ammonium glutarate,6 by hydrolysis of pentanedinitrile with acetic acid,6 and by oxidation of piperidine with hydrogen peroxide.7... 

Glutarimides may be regarded as oxidized piperidines, and many drugs containing this moiety are sedatives and anticonvulsants. A spiro derivative, alonimid (105) is such a sedative-hypnotic agent. It can be prepared by K t-butoxide catalyzed biscyano-ethylation of phenylacetonitrile, leading to 101. Alkaline hydrolysis produces tricarboxylic acid 102 which is smoothly Converted to the glutaric acid anhydride (103) with acetic anhydride. Friedel-Crafts... 

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