alpha-Phenetylamine resolution

An introductory organic chemistry experiment
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Addison Ault Cornell College Mount vernon, Iowa

Several laboratory manuals offer experiments involving the resolution of a racemic mixture1(1-4). We offer heer a different resolution which has been found to be convenient, relatively inexpensive, and to give a product of high optical purity. If only on enantiomer is desired the experiment can be done in one afternoon (plus half an hour of a previous laboratory period). To obtain both enantiomers, the experiment requires four to five laboratory periods. On a 0.2 molar scale, the cost per student for the amine and d-tartaric acid is about $1.20. Most students who have tried the experiment have been able to isolate the first enantiomer in at least 95% optical purity, although they are usually less successful with the other isomer. The procedure has been adaptet from that published by Theilacker and Wiunkler(5).

The Experiment

(-)-α-Phenylethylamine; Add 31.25 g of D-tartaric acid (0.208 mole) to 450 ml of methanol in a one-liter Erlenmeyer flask, and heat the mixture almost to boiling. To the hot solution add cautiously 25 g of D,L-α-phenylethylamine (26.6 ml; 0.206 mole),-1 too rapid addition will cause the mixture to boil over. Since crystallization occurs slowly, the solution must be allowed to stand at room temperature for about 24 hours. The (-)-amine-(+)-hydrogen tartrate separates as prismatic crystals.2
Collect the product by suction filtration and wash it with a little methanol. Yield: 18.1 grams (65%).
A second crop (3.8 grams) may be obtained by concentrating the combined mother liquor and washings to 225 ml, and allowing crystallization to proceed at room temperature for 24 hours.
Partially disolve the product (21.9 grams) in about 90 ml of water and add 12.5 ml of 50% sodium hydroxide solution in order to convert the amine salt to the free base. Extract the amine with ether, and dry the extract over anhydrous magnesium sulfate for about ten minutes. Remove most of the ether by heating the extract on the steam bath, and distill the residue (considerable foaming) to obtain (-)-α-phenylethylamine. Yield: 6.9 grams, 55%; bp: 184-186°; [α]D 27: -38.2° (lit.: [α]D22: -40.3° (5)).
(+)-α-Phenylethylamine: Allow the methanolic solution remaining from the isolation of the (-)-amine-(+)-hydrogen tartrate to evaporate to dryness (done most easily by leaving the solution in an evaporating dish in the hood overnight), and recover the remainder of the amine by treating the residual salt with sodium hydroxide, extracting with ether, and distilling as described above. Determine the specific rotation of the recovered amine.
The (+)-amine is isolated by treating a hot ethanolic solution of the recovered amine with an amount of sulfuric acid in ethanol slightly greater than that necesary to conver the excess (+)-amine to the neutral sulfate salt. The resulting crystals of (+)-α-phenyletylamine sulfate yield the (+)-amine.
Dissolve 12.5 g (0.103 mole) recovered amine, [α]D27: +24.5°, in 88 ml of 95% ethanol. (This solution contains 0.062 mole excess (+)-amine, based on [α]D22: +40.7° for the pure (+)-amine, and 0.041 mole racemic amine). Heat the solution to boiling and add to it a solution of concentrated sulfuric acid (3.2 g of 98% H2SO4; 0.032 mole H2SO4) in 180 ml of 95% ethanol. After allowin the mixture to cool slowly to room temperature, collect the crystalline (+)-amine sulfate by suction filtration and wash it thoroughly with ethanol. Yield: 7.8 g (74%).
Isolate the free (+)-amine as described above (treatment with sodium hydroxide, extraction, and distillation) using 40ml of water and 5 ml of 50% sodium hydroxide for each 10 g of the sulfate salt. Yield: 4.4 g (59%); bp: 184-186°; [α]D27: +38.3° (lit.: [α]D22: +40.67° (5)).
We have used this experiment early in the first semester of the introductory organic chemistry course. It clarifies several of the concepts of optical isomerism, a topic which we prefer to discuss at this time. The demands upon technique are modest, so this experiment is also a means of introducing some of the procedures used in recrystallization, extraction, and distillation. Students like the experiment because they consider the optical purity of their product a valid measure of their skill in the laboratory.


1Eastman Kodak Company practical grade DL-α-methylbenzylamine.
2Sometimes a substance separates in the form of very fine needles. In this event, warm the mixture to dissolve the crystals and allow it to cool again. If possible, seed the solution with the prismatic crystals. Workup of the needle-like crystals give α-phenylethylamine of [α]D26 -19 to -21°.

Litterature Cited

(1) Helkamp, G. K., and Johnson, H. W., "Selected Experiments in Organic Chemistry," W. H. Freeman & Co., San Francisco, 1964, p. 97 (sec.-butyl amine).
(2) MacKenzie, C. A., "Experimental Organic Chemistry," 2nd ed., Prentice-Hall. Inc., Englewood Cliffs, New Jersey, 1962, p. 221 (mandelic acid).
(3) Popp, F. D., and Schultz, H. P., "Organic Chemical Preparations," W. B. Saunders Company, Philadelphia, 1964, p. 186 (α-methylbutyric acid).
(4) Brewster, R. Q., VanderWerf, C. A., and McEwen, W. E., "Unitized Experiments in Organic Chemistry," 2nd ed., D. Van Nostrand Company, Princeton, New Jersey, 1964, p. 140 (sec.-octyl hydrogen phthalate) and p. 217 (mandelic acid).
(5) Theilaker W., and Winkler, H.-G., Chem. Ber. 87, 691 (1954).