How can diastereomers be separated?

1 Answer
Oct 30, 2014

Diastereomers have different physical properties, so you can separate them like any two different molecules.

Here are the most common methods.


Diastereomers have different solubilities. You could find a solvent in which the solubilities are different enough.

Then one diastereomer will recognize its own mates and crystallize before the other one.

Column Chromatography

Diastereomers have different degrees of attraction to a stationary phase. You can separate them on a suitable column.

HPLC (High Performance Liquid Chromatography)

HPLC uses pressure to force a solvent containing the sample mixture through a column filled with a solid stationary phase.

Other chromatographic methods are

Thin Layer Chromatography
Gas Chromatography

In all these cases, you can use optically active stationary phases to improve the separation. But they are often quite expensive.

But probably the most efficient method for separating diastereomers is

SCF (Supercritical Fluid Chromatography)

This technique uses CO₂ at temperatures above 31 °C and pressures above 73 atm as the mobile phase. Under these conditions, CO₂ is a supercritical fluid. It expands to fill its container like a gas but has a density like that of a liquid.