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How can stereoisomers be separated or distinguished?

Stereoisomers have the same chemical formula but different 3D arrangements, so special methods are needed to separate or identify them.


1. Geometrical Isomers (cis/trans, fac/mer)

  • Separation Methods:
    • Crystallization – cis and trans forms often have different solubilities.
    • Chromatography – sometimes cis/trans isomers separate on silica gel or HPLC.
  • Distinguishing Methods:
    • UV-Vis or IR spectroscopy – different spatial arrangements can shift absorption bands.
    • NMR spectroscopy – different environments of protons or carbons give distinct signals.

2. Optical Isomers (Enantiomers)

  • Separation Methods (Enantiomeric Resolution):
    • Chiral chromatography – uses a chiral stationary phase to separate enantiomers.
    • Using chiral reagents – react enantiomers with another chiral compound to form diastereomers, which can be separated (diastereomers have different physical properties).
    • Crystallization with chiral acids/bases – sometimes only one enantiomer crystallizes first.
  • Distinguishing Methods:
    • Polarimetry – measures the rotation of plane-polarized light.
      • One enantiomer rotates light clockwise (+), the other counterclockwise (–).
    • Circular Dichroism (CD) – shows differences in absorption of left- vs. right-circularly polarized light.
    • NMR with chiral shift reagents – enantiomers give separate signals in a chiral environment.

3. Notes

  • Geometrical isomers differ in position, optical isomers differ in handedness.
  • Sometimes a combination of chromatography, spectroscopy, and crystallization is used to separate and identify stereoisomers.

In short:

  • Geometrical isomers → separated by solubility or chromatography, identified by NMR/IR.
  • Optical isomers → separated by chiral methods, identified by polarimetry or circular dichroism.

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