A Publication
of Reliable Methods
for the Preparation
of Organic Compounds
Annual Volume
Org. Synth. 1943, 23, 60
DOI: 10.15227/orgsyn.023.0060
[Glutaric acid, β-methyl-]
Submitted by Robert E. Kent and S. M. McElvain.
Checked by Lee Irvin Smith and G. A. Boyack.
1. Procedure
A. α,α'-Dicyano-β-methylglutaramide. In a 6-l. flask, 520 g. (6.2 moles) of recrystallized cyanoacetamide (Note 1) is dissolved in 3.4 l. of water, and the solution is cooled to 10° and filtered if it is not clear (Note 2). While the flask is shaken constantly, 137.5 g. (3.1 moles) of freshly distilled acetaldehyde and 20 ml. of piperidine are added successively to the solution. After the mixture has stood at room temperature for 2 hours, the flask is transferred to an ice-salt bath and the mixture is partially frozen. During this operation, the flask should be shaken frequently. After 30 minutes, α,α'-dicyano-β-methylglutaramide begins to deposit, and when the precipitation is complete (about 1 hour), the mixture is allowed to come to room temperature in order to melt the ice that is present. The precipitate is then filtered with suction and washed thoroughly with cold distilled water. The yield is 420–425 g. (71%) of a white, powdery solid which melts at 152–157° (Note 3).
B. β-Methylglutaric acid. In a 5-l. flask are placed 400 g. of the amide and 1 l. of concentrated hydrochloric acid; the mixture is warmed on a steam bath until solution is complete, after which it is diluted with 1 l. of water and refluxed for 8 hours. The amber-colored solution is saturated with sodium chloride and extracted with five 600-ml. portions of ether. The combined ether extracts are dried for 1 hour over phosphorus pentoxide, and the solvent is removed by distillation. The residue, crude β-methylglutaric acid, weighs 238–240 g. (80%) and melts at 79–82° with previous softening. This product is recrystallized from about 250 ml. of 10% hydrochloric acid. The recovery is about 90% (Note 4), and the purified product melts at 85–86°.
2. Notes
1. Ammonia exerts a hindering effect on this condensation, and the yield is greatly reduced when crude cyanoacetamide is used.
2. At 10°, cyanoacetamide sometimes crystallizes. The mixture should not be filtered until it is certain that the precipitate contains no cyanoacetamide. Any cyanoacetamide that separates redissolves quickly after the acetaldehyde and piperidine have been added.
3. This amide is insoluble in the usual solvents, but it may be further purified, if desired, by trituration with dilute hydrochloric acid, followed by washing with hot absolute ethanol. It then melts sharply at 160–161°.
4. The checkers used one-tenth of the specified amounts of reagents. They obtained, in two runs, the following average yields of products: crude α,α'-dicyano-β-methylglutaramide, m.p. 152–157°, 75%; crude β-methylglutaric acid, m.p. 79–82°, 78%; purified β-methylglutaric acid, m.p. 84–85°, 80% (recovery). In the second run, however, the yields (except for the recovery in the recrystallization) were slightly higher than those given for the larger runs.
3. Discussion
The above method is adapted from the procedure of Day and Thorpe.1 β-Methylglutaric acid has been prepared by hydrolysis of β-methylglutaronitrile;2 by condensation of crotonic ester with ethyl sodiocyanoacetate,3 and with sodiomalonic ester;4,5 and by condensation of acetaldehyde with malonic ester.6
This preparation is referenced from:

References and Notes
  1. Day and Thorpe, J. Chem. Soc., 117, 1465 (1920).
  2. Blaise and Gault, Bull. soc. chim. France, (4) 1, 88 (1907).
  3. Howles, Thorpe, and Udall, J. Chem. Soc., 77, 948 (1900); Darbishire and Thorpe, J. Chem. Soc., 87, 1716 (1905).
  4. Hunsdiecker, Ber., 75B, 1199 (1942).
  5. Auwers, Kobner, and Meyenberg, Ber., 24, 2887 (1891).
  6. Knoevenagel, Ber., 31, 2585 (1899).

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

sodiomalonic ester

Malonic Ester

ethanol (64-17-5)

acetaldehyde (75-07-0)

hydrochloric acid (7647-01-0)

ammonia (7664-41-7)

ether (60-29-7)

sodium chloride (7647-14-5)

piperidine (110-89-4)


β-Methylglutaric acid,
Glutaric acid, β-methyl- (626-51-7)


ethyl sodiocyanoacetate

phosphorus pentoxide (1314-56-3)