Coffee, Tea, or...

Cocoa
Donald L. Pavia
Western Washington State College
Bellingham, 98225
A trio of experiments including
the isolation of theobromine from cocoa

There are a number of natural products having a source
widely available and a method of isolation simple enough
to be adaptable to elementary organic experiments. Such
experiments teach technique without involving complicat-
ed reactions and are thus particularly suitable for the
early stages of organic laboratory. Caffein from tea (1),
coffee (2), cola (lb, 3), and No-Doz (4) are four such ex-
periments widely used. In our laboratory we have found
student interest is heightened whenever it is possible to
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hydrogen is quite acidic making theobromine freely solu-
ble in basic solution and allowing it to form double salts
with the salts of organic acids such as sodium salicylate.
Since such salts enhance the water solubility of theobrom-
ine, it is in this form that the alkaloid has found pharma-
ceutical use. However, as a central nervous system stimu-
lant and diuretic, it is decidely less active than caffein.
Most theobromine, isolated in large quantities during the
production of chocolate and cocoa, is converted to caffein,

offer the student free choice among several parallel exper- a superior commercial pharmaceutical product.
iments with related outcomes that may be discussed and In the experimental section which follows, a simple
compared. Three experiments of comparable difficulty in- method for the isolation of crude theobromine is de-
clude: caffein from tea leaves, caffein from coffee, and the scribed. The principal difficulty in the isolation and puri-
experiment described below, the isolation of theobromine fication of theobromine is due to the fact that it is spar-
from cocoa. Not only are these beverages chemically relat-
ed, but they are of enormous social importance. In fact,
the experiments can be enlivened by many relevant his- 5000 5000 2000 1500 1000 900
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R =
H Theobromine
R CH3 Caffein
=

Theobromine is a purine alkaloid differing from caffein

by only one methyl group. However, that single methyl
group confers such different properties to caffein that
theobromine makes an interesting study in contrast. Caf-
fein is a strictly basic compound and forms a hydrochlo-
ride salt.

Caffein
Hydrochloride

H
CH:i

Theobromine, however, forms salts where it behaves both

as an acid and a base depending on conditions. The imide

Volume 50, Number 11, November 1973 / 791

 ingly soluble in most solvents at room temperature. Even
when boiling, the only solvents of reasonable capacity are
water, chloroform, aniline, and trichloroethylene. Water is
a very inconvenient extraction solvent. This is mainly be-
cause cocoa does not really dissolve in water, but makes
beautiful frothy emulsions which are a delight to drink
but difficult if not impossible for the beginning student to
handle. The procedure here gives about 300-350 mg of
crude theobromine, corresponding to a 1.5-2% yield of the
alkaloid (weight percent) from cocoa.
Students doing parallel experiments with caffein should
be encouraged to compare their results. That theobromine
and caffein are distinct can be shown by tic comparison
(2a). Silica Gel G microslides using 9:1 chloroform/etha-
nol (95%) as a developing solvent work quite well for this
purpose. The solubility behavior of both caffein and theo-
bromine should be compared. The infrared spectra are
also quite distinct (6).
The best way to characterize theobromine is to convert
it to caffein by use of dimethyl sulfate in basic solution.
CH:, CHa
A suitable derivative of caffein is its salicylate (mp
134-137°C) (lb).
Because of the insolubility of theobromine, infrared
spectra are best determined as KBr pellets or Nujol mulls.
An interesting feature of comparison in the spectra of the
two alkaloids is that theobromine apparently exists largely
in the enol form while caffein does not (and cannot).
The nmr spectrum of caffein (la) is easily obtained, but
theobromine is insoluble in all reasonable solvents. It can
be dissolved in D20/NaOD, but this medium forms the
anion and exchange of the imide hydrogen takes place.
792 / Journal of Chemical Education
Isolation and Purification of Theobromine
Stir 20 g of Hershey’s Cocoa and 6 g MgO into a 250 ml beaker
containing 40 ml H2O and 20 ml MeOH. Heat this mixture
(steam bath) with frequent stirring until the mass becomes semi-
dry and crumbly (45-50 min). Transfer the semi-solid mass to a
500-ml 3-neck flask and add 150 ml CHCI3. Heat under reflux for
30 min and then filter the mixture (9.0 cm Buchner) while the so-
lution is still hot. Crumble the solid residue and return it to the
flask for a second extraction. Combine the filtrates (note that the
CHCI3 must be warm during all transfer operations or the prod-
uct will coat out on the flask surfaces) and remove the CHCI3 by
simple distillation. When 5-10 ml CHCI3 remain, cool, and add
60 ml diethyl ether to the distillation flask. Stopper and let stand
overnight. Carefully collect the fine microcrystalline precipitate
by gravity filtration through a cone of fine porosity paper. Wash
the product with 5 X 10 ml ether. About 0.3 g crude theobromine
is obtained, mp 351°C (sublimes 290-5°C); some residue will re-
main on melting.
In view of the small amounts isolated the theobromine
is best converted directly to the more easily purified caf-
fein (see below). However, theobromine may be recrystal-
lized from boiling water (solubility 1 g/150 ml) using de-
colorizing charcoal: mp 352-4°C. It may also be purified
by sublimation.
Conversion to Caffein
Dissolve the crude theobromine in a minimum (~5 ml) of 10%
sodium hydroxide in a 50-ml Erlenmeyer. Add 1 ml dimethyl sul-
fate (TOXIC, use HOOD and prevent contact with skin), stop-
per, and shake gently and constantly for about 20 min. Extract
the product with CHCI3 (2 X 20 ml) and dry over sodium sulfate.
Evaporate the CHC13 using a steam bath in the hood and recrys-
tallize the crude, residual caffein from benzene-petroleum ether
(60-90°C). Collect the crystals (Buchner) and dry them (mp 235-
7°C). The conversion goes in >90% yield.
Literature Cited
(1) (a) Ikan, R., “Natural Products—A Laboratory Guide,” Academic Press, New York,
1969, p. 182. (b) Helmkamp, G. K., and Johnson, H. W., Jr., “Selected Experi-
ments in Organic Chemistry,” 2nd ed., Freeman, San Francisco, 1968, pp. 157-8.
(c) Baldwin, J., “Experimental Organic Chemistry," 2nd ed., McGraw-Hill, New
York, 1970, pp. 1-3, 14-16. (d) Adams, R., Johnson, J. R., and Wilcox, C. F., Jr.,
“Laboratory Experiments in Organic Chemistry,” 6th ed., Macmillan, New York,
1970, p. 108. (e) Fishel, D. L., and Fort, R. C., “Modern Experimental Organic
Chemistry,” Macmillan, New York, 1971, pp. 58-9.
(2) (a) O’Connor, R., J. CHEM. EDUC., 42, 492 (1965). (b) Henry, T. A., “The Plant
Alkaloids," 2nd ed., Blakiston’s, Philadelphia, 1924, pp. 329-35 (Chap. VIII). (c)
Paech, K., and Tracey, M. V., "Moderne Methoden der Pflanzenanalyse,”
Springer-Verlag, Berlin, 1955, Vol IV, pp. 300-3.
(3) Laswick, J. A., and Laswick, P. H., J. CHEM. EDUC., 49,708 (1972).
(4) Moye, Aldred L., J. CHEM. EDUC.. 49, 194 (1972).
(5) (a) Ray, 0. S., “Drugs, Society, and Human Behavior,” Mosby, Saint Louis, 1972,
Chap. 8. (b) Taylor, N., “Narcotics—Nature's Dangerous Gifts,” Dell Publishing
(r6270), New York, 1970, Chap. 8. (c) Taylor, N., “Plant Drugs that Changed the
World,” Dodd, Mead, and Company, Apollo Editions rA-304, New York, 1965,
pp. 55-7.
(6) Blout, E. R., and Fields, M„ J. Amer. Ckem. Noe.. 72, 479 (1950).