Res. Chem. Intermed.
, Vol. 33, No. 7, pp. 663–673 (2007)
Also available online - www.brill.nl/rci
Stereoselectivity of (–)-(1R,2S)-2-methylamino-1-phenyl-
MARTINA ASTROVÁ, LADISLAV KURC and LIBOR
Department of Organic Technology, Institute of Chemical Technology in Prague, Technická 5,
166 28 Praha 6, Czech Republic
Received 2 April 2007; accepted 15 June 2007
Abstract—Stereoselectivity of reductive amination of (R)-1-hydroxy-1-phenylpropan-2-one by
methylamine was studied. From the four isomers possible, only two are produced by this reaction.
These are marked as (–)-(1R,2S)-ephedrine (desired product) and (+)-(1S,2R)-ephedrine. The reaction
stereoselectivity depends both on the type of the catalyst and reaction conditions. The most suitable
type is the supported platinum. However, this catalyst rapidly deactivates. With a decreasing activity
of Pt catalyst, the stereoselectivity decreases. It is also decreased during the production of the second
liquid phase (water) in the reaction mixture.
Keywords: Stereoselectivity; ephedrine; hydrogenation; liquid phase.
The 2-methylamino-1-phenylpropan-1-ol molecule has two asymmetric centers and
exists in four optically active forms. Isomers with arrangement of substituents
on asymmetric carbons analog to erythrose are called ephedrines. Their dia-
stereoisomers with arrangement analog to threose are called pseudoephedrines.
Both ephedrine and pseudoephedrine can exist in two enantiomeric forms. This
implies the existence of two racemates, (±)-ephedrine and (±)-pseudoephedrine
(–)-(1R,2S)-Ephedrine and (+)-(1S,2S)-pseudoephedrine are used as pharmaceu-
tical substances. Recently, the preparation of these substances is based on reductive
Abbreviations and symbols: V, volume of liquid phase (l); x,conversion(%);c, concentration
(mol/l); n, molar amount (mol); r
, instantaneous substance production rate (mol/g
k, constant proportional to rate constant of substance production (l/min); m, weight (g); t, reaction
time (min); ee, reaction stereoselectivity (%);
, indices of experimental points.
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