Stereogenic Nitrogen

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A close examination of the ephedrine and pseudoephedrine isomers suggests that another stereogenic center, the nitrogen, is present. As noted earlier, single-bonded nitrogen is pyramidal in shape, with the non-bonding electron pair pointing to the unoccupied corner of a tetrahedral region. Since the nitrogen in these compounds is bonded to three different groups, its configuration is chiral. The non-identical mirror-image configurations are illustrated in the following diagram (the remainder of the molecule is represented by R, and the electron pair is colored yellow). If these configurations were stable, there would be four additional stereoisomers of ephedrine and pseudoephedrine. However, pyramidal nitrogen is normally not configurationally stable. It rapidly inverts its configuration (equilibrium arrows) by passing through a planar, sp²-hybridized transition state, leading to a mixture of interconverting R and S configurations. If the nitrogen atom were the only chiral center in the molecule, a 50:50 (racemic) mixture of R and S configurations would exist at equilibrium. If other chiral centers are present, as in the ephedrin isomers, a mixture of diastereomers will result. In any event, nitrogen groups such as this, if present in a compound, do not contribute to isolable stereoisomers.

Figure 1: An Example of a stereogenic nitrogen in a chiral molecule.

Contributors

William Reusch, Professor Emeritus (Michigan State U.), Virtual Textbook of Organic Chemistry