The Cocaine Diastereoisomers

Table 1.
Melting point data °C.

Compound	Findlay4	Sinnema et al.5	Willstätter et al.7	Merck9	This Work
(-)-Cocaine	-	-	-	98	96-97
(+)-Cocaine	-	-	98	-	-
(±)-Cocaine	79-80	-	79-80	-	74-75
(-)-Cocaine HCl	-	-	192	195	194-196
(±)-Cocaine HCl	187	-	187	-	186-188
(+)-Pseudococaine	-	-	43-45	47	-
(±)-Pseudococaine	81.5	-	81.5	-	oil
(+)-Pseudococaine HCl	-	-	205	210	208-210
(±)-Pseudococaine HCl	205.5	-	205-206	-	202-204
(±)-Allococaine	93-95	95-97	-	-	94-96
(±)-Allococaine HCl	oil	oil	-	-	oil
(±)-Pseudoallococaine	82-84	83-84	-	-	oil
(±)-Pseudoallococaine HCl	201.5	209-210	-	-	203-205

\\\

Proton Nuclear Magnetic Resonance

¹H-NMR Spectra
(in CDCl₃)

Fig. 4.	Cocaine
Fig. 5.	Pseudococaine
Fig. 6.	Allococaine
Fig. 7.	Pseudoallococaine

Proton NMR spectra of the diastereoisomeric cocaines are significantly different. Major differences are seen in the chemical shifts associated with the respective C-3 protons. In addition, the coupling patterns that arise from the vicinal coupling of C-2 and C-4 protons with the C-3 proton are first order and relate nicely to the Karplus equation⁵.

That the diastereoisomeric cocaines, can easily be distinguished by observation of the chemical shifts and coupling patterns associated with the C-3 proton does not imply that other differences do not exist. In fact, virtually every proton in these molecules exhibits a different chemical shift or coupling pattern

COCAINE

1. Findlay, S. P., J. Am. Chem. Soc., 76, 2855-2862 (1954)
2. Findlay, S. P., J. Org. Chem., 21, 711 (1956)
3. Findlay, S. P., J. Org. Chem., 22, 1385-1394 (1957)
4. Findlay, S. P., J. Org. Chem., 24, 1540-1550 (1959)
5. A. Sinnema, L Maat, AJ vd.Gugten, HC Beyerman, Rec. Trav. Chim. Pays-Bas 87, 1027-1041 (1968)
6. Robinson, R., Journal of the Chemical Society (London), 111, 762-768 (1917)
7. Willstätter, R., Wolfes, O., and Mäder, H., Justus Liebigs Annalen der Chemie, 434, 111-139 (1923)
8. Fulton, C. C., Modern Microcrystal Tests for Drugs, Wiley, New York, 1969, pp. 21-24.
9. The Merck Index, 9th ed., 1976, Merck and Co., Rahway, N.J.
10. Fulton, C. C., Modern Microcrystal Test for Drugs, Wiley, New York, 1969, pp. 318-19.
11. Clarke, E. G. C., Isolation and Identification of Drugs, Pharmaceutical Press, London, 1971, pp. 139-41.
12. Fulton, C. G., Modern Microcrystal Tests for Drugs, Wiley, New York, 1969, p. 301.
13. Cooper, D. A. and Allen, A. C., "A Mechanistic Interpretation of the Mass Spectrum of Cocaine",
    31st Annual Meeting of the American Academy of Forensic Sciences, Atlanta, Georgia, Feb. 1979.
14. Eliel, E. L., Stereochemistry of Carbon Compounds, McGraw-Hill, New York, 1962, pp. 43-47.

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