MANDELIC ACID

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.
Either of two methods may be used to extract the mandelic acid from the ammonium
chloride.
(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.
12. Benzene works almost as well as toluene; xylene can also be used.
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).
Working with Hazardous Chemicals
The procedures in Organic Syntheses are intended for use only by persons with proper
training in experimental organic chemistry. All hazardous materials should be handled
using the standard procedures for work with chemicals described in references such as
"Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C.,
2011; the full text can be accessed free of charge
athttp://www.nap.edu/catalog.php?record_id=12654). All chemical waste should be
disposed of in accordance with local regulations. For general guidelines for the
management of chemical waste, see Chapter 8 of Prudent Practices.
In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red
"Caution Notes" within a procedure. It is important to recognize that the absence of a
caution note does not imply that no significant hazards are associated with the
chemicals involved in that procedure. Prior to performing a reaction, a thorough risk
assessment should be carried out that includes a review of the potential hazards
associated with each chemical and experimental operation on the scale that is planned
for the procedure. Guidelines for carrying out a risk assessment and for analyzing the
hazards associated with chemicals can be found in Chapter 4 of Prudent Practices.
The procedures described in Organic Syntheses are provided as published and are
conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of
Directors do not warrant or guarantee the safety of individuals using these procedures
and hereby disclaim any liability for any injuries or damages claimed to have resulted
from or related in any way to the procedures herein.
The paragraphs above were added in September, 2014. The statements above do not
supersede any specific hazard caution notes and safety instructions included in the
procedure.
3. Discussion
Mandelic acid can be prepared by the hydrolysis of amygdalin with sulfuric acid1 or
of mandelonitrilewith hydrochloric acid.2 The mandelonitrile can be prepared by the
action of hydrocyanic acid on benzaldehyde,3 and by the action of sodium or potassium
cyanide on the sodium bisulfite addition product of benzaldehyde.4 The procedure
described differs from earlier methods in that the sodium bisulfite addition compound
of benzaldehyde is prepared in the presence of sodium cyanide and the nitrile is formed
immediately.