Org. Synth. 1925, 5, 69; Org. Synth. 1930, 10, 58
DOI: 10.15227/orgsyn.010.0058
GLUTARIC ACID
[(A) (from Trimethylene Cyanide)]
Submitted by C. S. Marvel and W. F. Tuley.
Checked by H. T. Clarke and E. E. Dreger.
1. Procedure
In a
2-l. round-bottomed flask are placed
100 g. (1.06 moles) of trimethylene cyanide (p. 536) and
500 g. (424 cc., 4.8 moles) of hydrochloric acid (sp. gr. 1.18). The mixture is refluxed for about four hours and then the solution is evaporated to dryness, preferably under reduced pressure. The dry residue, consisting of
glutaric acid and
ammonium chloride, is extracted with about
300 cc. of boiling ether. The
ether solution is filtered and the residue is further extracted with two
100-cc. portions of boiling ether. The combined
ether extracts containing the
glutaric acid are evaporated
(Note 1) to about 150–200 cc., whereupon the acid begins to crystallize. Then
1 l. of benzene (Note 2) is added, and the mixture is heated until the
glutaric acid dissolves. On cooling in an
ice-salt bath, the acid crystallizes. The first crop weighs
103–105 g. (Note 3). The filtrate is concentrated to about one-third its original volume and cooled, whereupon a second crop of
13–14 g. of pure
glutaric acid is obtained. The total yield is thus
116–119 g. (
83–85 per cent of the theoretical amount) of a product melting at
97–98° (Note 4).
2. Notes
1.
Most of the
ether can be recovered by concentrating the solution in a flask attached to a
condenser set for distillation.
2.
The
glutaric acid may be directly extracted from the
ammonium chloride with
benzene, but on a small scale this is less satisfactory than the procedure given.
3.
When the
benzene solution is chilled to 0° or lower, almost all the
glutaric acid separates in the first crop of crystals.
4.
It is reported that
glutaric acid can be easily and cheaply prepared by the oxidation of
cyclopentanone according to the following procedure, which is similar to that for the preparation of
adipic acid from
cyclohexanone—compare
p. 18. The oxidation needs careful control, for if it gets out of hand
succinic acid results.
In a 2-l. round-bottomed, three-necked flask fitted with a stirrer and two large-bore condensers are placed 200 cc. of 50 per cent nitric acid and 0.25 g. of vanadium pentoxide. The flask is heated to 65–70° in a water bath (thermometer in the water), and 1 cc. of cyclopentanone is added. Oxidation is indicated by the production of brown fumes. The water bath is removed, and 42 g. (less the 1 cc.) of the cyclic ketone is added from a dropping funnel through the condenser at the rate of a drop every three seconds. The heat of the reaction keeps the flask at about 70°. If the temperature drops, oxidation ceases until the ketone has accumulated, when it may proceed almost explosively. In such a case, or if the temperature is higher, much succinic acid is formed. After addition has been completed, the water bath is replaced and the mixture heated to boiling. The contents of the flask are poured into an evaporating dish (Hood), and the volume reduced one-half. When cold, the acid is filtered and the operation repeated twice; the last time the acid is yellowish, and the color is removed by washing with dilute hydrochloric acid. The crude glutaric acid is white and weighs 50–55 g. (80–85 per cent); m.p. 92–94°. If any succinic acid is present owing to lack of proper control, it separates in the first crop. It is more convenient to allow the mother liquors from several runs to accumulate and work them up separately; from each run 2–3 g. more of glutaric acid may be so obtained. Further purification is accomplished, if desired, by crystallization from benzene. The acid as prepared above always contains traces of nitric acid, but is satisfactory for conversion into the anhydride. If the catalyst is omitted, the yield is less by 10 per cent. (C. F. H. Allen and W. L. Ball, private communication).
[(B) (from Ethyl Malonate)]
Submitted by T. J. Otterbacher
Checked by F. C. Whitmore and F. L. Carnahan.
1. Procedure
Ethyl Propane-1,1,3,3-tetracarboxylate.—To a mixture of
1600 g. (1510 cc., 10 moles) of ethyl malonate (Note 1) and
400 g. of 40 percent formalin (5.3 moles) in a
5-l. round-bottomed flask, cooled to 5° by immersion in ice, is added
25 g. (35 cc.) of diethylamine. The mixture is then allowed to come to room temperature and remain for fifteen hours, after which the flask is heated under a
reflux condenser on a boiling water bath for six hours. The aqueous layer is then separated, and the residue is distilled under reduced pressure
(Note 2) from a
3-l. special Claisen flask (p. 130). The
ester distils at
190–200°/12 mm. (
210–215° /20 mm.). The yield
(Note 3) is
1000 g. (
61 per cent of the theoretical amount).
Glutaric Acid.—A mixture of 125 g. (0.37 mole) of the above product, 125 cc. of concentrated hydrochloric acid, and 125 cc. of water is heated (Note 4) in a 1-l. flask under a reflux condenser until it becomes homogeneous (six to eight hours). The contents of the flask are then evaporated to dryness, and the residual glutaric acid is transferred to a 100-cc. Claisen flask and distilled under diminished pressure. The fraction boiling at 185–195° /10 mm. is collected. It is moistened with water (Note 5) and heated gently, after which it is dried at 30°. On recrystallization from benzene, it separates in colorless needles, m.p. 96–97°. The yield is 38–40 g. (76–80 per cent of the theoretical amount).
2. Notes
1.
The
ethyl malonate used was a fraction of the technical grade boiling over a 3° range under diminished pressure.
2.
The ester is distilled slowly at first in order to vaporize the water at a temperature below 50°.
3.
The high-boiling residue (500 g.) is stated
1 to contain considerable amounts of
ethyl pentanehexacarboxylate.
Directions are also available for the preparation of
ethyl propane-1,1,3,3-tetracarboxylate in high yield from
ethyl malonate,
paraformaldehyde, and alcoholic
potassium hydroxide.
2 Prior to distillation of the ester a little
hydrochloric acid is added to destroy the catalyst.
4.
In order to prevent loss of material through the condenser by bumping, the flask should be heated in an
oil bath at 115° or its contents stirred vigorously.
5.
The product is moistened to convert any anhydride, formed at the high temperature of distillation, into the acid.
3. Discussion
Glutaric acid can be prepared by the hydrolysis of
trimethylene cyanide with acids or alkalies;
3 the hydrolysis of
methylene dimalonic ester4 or
methylene dicyanoacetic ester;
5 and the oxidation of
cyclopentanone with
nitric acid6 or catalytically.
7 Glutaric acid can also be prepared from
methylcyclohexane by catalytic oxidation,
8 and from
pentamethylene glycol by oxidation with permanganate.
9
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
ester
cyclic ketone
methylene dimalonic ester
methylene dicyanoacetic ester
hydrochloric acid (7647-01-0)
Benzene (71-43-2)
ether (60-29-7)
ammonium chloride (12125-02-9)
formalin (50-00-0)
Adipic acid (124-04-9)
nitric acid (7697-37-2)
Cyclohexanone (108-94-1)
vanadium pentoxide
Succinic acid (110-15-6)
potassium hydroxide (1310-58-3)
Trimethylene cyanide (544-13-8)
Cyclopentanone (120-92-3)
ethyl malonate (1071-46-1)
Glutaric acid (110-94-1)
Ethyl propane-1,1,3,3-tetracarboxylate
diethylamine (109-89-7)
ethyl pentanehexacarboxylate
methylcyclohexane (108-87-2)
pentamethylene glycol (111-29-5)
paraformaldehyde (30525-89-4)
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