Submitted by B. B. Corson, Ruth A. Dodge, S. A. Harris, and J. S. Yeaw.
Checked by C. S. Marvel and M. M. Brubaker.
1. Procedure
In a
4-l. wide-mouthed glass jar, fitted with a
mechanical stirrer, is placed a solution of
150 g. (3 moles) of sodium cyanide (Note
1) in 500 cc. of water and
318 g. (3 moles) of u.s.p. benzaldehyde. The stirrer is started, and
850 cc. of a saturated solution of sodium bisulfite (Note
2) is added to the mixture, slowly at first and then in a thin stream. The time of addition is ten to fifteen minutes. During the addition of the first half of this solution, 900 g. of cracked ice is added to the reaction mixture, a handful at a time. The layer of
mandelonitrile which appears during the addition of the sulfite solution is separated from the water in a
separatory funnel. The water is extracted once with about
150 cc. of benzene, the
benzene is evaporated, and the residual
mandelonitrile is added to the main portion.
The crude
nitrile (about 290 cc.) is placed at once (Note
3) in a
25-cm. evaporating dish, and
425 cc. of c.p. concentrated hydrochloric acid (sp. gr. 1.19) is added. The hydrolysis is allowed to proceed in the cold (Note
4) for about twelve hours, after which the mixture is heated on a
steam bath to remove the water and excess
hydrochloric acid. After heating for five to six hours it is advisable to cool the mixture (Note
5) and filter the
ammonium chloride and
mandelic acid mixture that separates. The filtrate is then evaporated to dryness. This residue is added to the solid material obtained before. The product is deeply colored and must be dried in the air and light for at least twenty-four hours. The total yield of the crude
mandelic acid-ammonium chloride mixture is 370–390 g., depending on the amount of moisture. The mixture of
ammonium chloride and
mandelic acid is ground in a
mortar, transferred to a
2-l. flask, and washed twice with
750-cc. portions of cold benzene (Note
6). The insoluble portion is transferred to a
suction funnel and sucked dry.
(
A)
Extraction with Benzene.—The
mandelic acid is separated from the
ammonium chloride by extraction with hot
benzene. This is best done by dividing the solid mixture into ten approximately equal parts (Note
7). One of these portions is placed in a flask with
1 l. of boiling benzene. After a few minutes the hot
benzene solution is decanted through a suction funnel (Note
8). The filtrate is cooled in an
ice bath and the
mandelic acid that crystallizes is filtered with suction. The
benzene is returned to the extraction flask containing the residue from the first extraction, and a new portion of the
ammonium chloride-mandelic acid mixture is added and extracted as before. The process is repeated until the
mandelic acid is completely removed from the
ammonium chloride (Note
9).
The yield of pure white
mandelic acid melting at
118° is
229–235 g. (
50–52 per cent of the theoretical amount based on
benzaldehyde).
(
B)
Extraction with Ether (Note
10).—The solid mixture is transferred to a 2-l. flask and shaken ten minutes with
750 cc. of ether. The ether solution is decanted through a
suction filter and the solid thrown onto the filter and pressed dry. The solid is then returned to the flask and shaken with
400 cc. of ether. This mixture is filtered by suction and the solid washed twice on the filter with
250-cc. portions of ether. Each portion is allowed to drain through the filter several times while the solid is kept porous with a
spatula. The combined ether filtrate is then filtered through an
ordinary funnel (Note
11). The ether solution is placed in a
3-l. round-bottomed flask, and
750 cc. of toluene (Note
12) is added. The mixture is distilled on a steam bath through an
efficient fractionating column as long as it distils easily, and about 1100–1400 cc. of distillate is collected. The temperature of the vapor rises to about 70°. The mixture is then heated over a free flame until the temperature in the column is 95°; about 300 cc. distils (Note
13). The residual liquid is poured while still hot into a
large beaker immersed in ice water. The liquid (about 900 cc.) is stirred by hand until it has become a thick crystal mush. The cooling is continued for two hours with occasional stirring so as to bring the temperature down to 5–10°. The mixture is filtered with suction and the solid pressed dry. It is then thoroughly washed on the filter with
300 cc. of toluene in several portions (Note
14).
The yield is the same as that obtained by method (
A) (Note
15).
2. Notes
1. This reaction and the subsequent hydrolysis should be carried out in a
good hood as some
hydrogen cyanide is liberated. The
sodium cyanide used was the technical "cyan-egg," containing about 92–95 per cent of cyanide.
2. This saturated solution is best prepared by stirring
1500 g. of technical sodium bisulfite (97–100 per cent) with 2 l. of water and filtering to remove the excess salt. The specific gravity of this solution is 1.37–1.39.
3. The
mandelonitrile should be mixed with
hydrochloric acid as soon as it is separated from the water. This appears necessary in order to avoid a rapid conversion to the
acetal of benzaldehyde and
mandelonitrile, C6H5CH[OCH(CN)C6H5]2. Hence if it is allowed to stand long before the hydrolysis, the yield of
mandelic acid is reduced.
4. The hydrolysis can be carried out in the hot, but the final product may be deeply colored.
5. It is advisable to stir the mixture during the cooling in order to break up the lumps and thus obtain a product that can be more easily filtered.
6. If the crude product is not first washed with cold
benzene the final product is usually colored. Very little
mandelic acid is lost by this washing.
7. The entire amount of the
ammonium chloride-mandelic acid mixture may be boiled with the
benzene, but this gives a supersaturated solution of the acid in the
benzene and much difficulty is met in the filtration. The solubility of
mandelic acid in hot
benzene is approximately 1 g. in 50 cc.
It may be better to carry out the extraction in a
Soxhlet apparatus or an apparatus of the type described on
p. 375.
8. The funnel should be previously heated and have fairly large holes so as not to be clogged by the
mandelic acid that begins to crystallize as soon as the solution cools slightly. Only slight suction should be applied during filtration.
9. Usually two or three extractions of the
ammonium chloride residues after the addition of the last portion of the crude mixture are necessary in order to obtain all the
mandelic acid. On concentrating the
benzene used for the extraction, about 5 g. of impure
mandelic acid may be obtained. To diminish mechanical losses it is recommended that the same container be used to collect and crystallize the several filtrates.
10. The ether extraction method (
B) is quicker, especially when several runs are to be made.
Mandelic acid is obtained in the same yield by this method. The
benzene extraction may be better for small preparations, or when a single run is to be made.
11. An occasional water layer should be removed in a separatory funnel.
13. The temperature in the column is a better guide than the volume of distillate. A few porous chips should be added to prevent bumping. The
ether-
toluene solution should not stand long before distillation as
mandelic acid is apt to separate. The heating with steam and with the free flame should be done quickly since prolonged heating lowers the yield.
14. The mother liquors are worked up for
toluene, but it is not profitable to try to recover the small amount of impure
mandelic acid which they contain.
15. The following modification is suggested for small-scale operations: When the hydrolysis of
mandelonitrile is complete, the mixture is cooled, sufficient water is added to bring the solid matter into solution, and the solution is extracted thoroughly with ether. The ethereal solution is dried with
sodium sulfate, the ether is distilled off from a water bath, and the
mandelic acid, which does not at once solidify, is taken up in
benzene and allowed to crystallize (L. F. Fieser, private communication).
3. Discussion
Copyright © 1921-2002, Organic Syntheses, Inc. All Rights Reserved