The Slow Evaporation Method

This is the most successful method we have used for more than 100 compounds (more than 90% of the time)! The next method being slow cooling (from high temperature to Room Temperature or Low temperature, slowly).

The Method: The compound can be dissolved in a single solvent or mixture of two solvents and left for Slow Evaporation. It can be done either under atmospheric conditions or under inert atmosphere. The best containers to use are (in the order): centrifuge tube, NMR tube, test tube, round bottom flask, conical flask and beaker. Do not use too big container for the volume of solution you are handling.

The Solvents:

• Choose a solvent in which the compound is moderately soluble. -OR-
• Choose two solvents, in such a way that:
  1. Compound is soluble in one and insoluble in another
  2. The solvent polarities are not too apart (hexane-methanol is a bad example)
  3. The boiling point of the dissolving solvent is fairly less than the other solvent.

Some Details for two solvent method: Dissolve the compound in the solvent that can dissolve. The volume depends on the amount of compound you are using. About 1-5 ml per 0.1 g may be a good starting point. Then add the other solvent slowly with good mixing. When you are reaching near the critical mixture, some precipitation will form and take a longer time to dissolve. If it does not dissolve, try the following:

• Warm the mixture slightly (always mixing causes cooling),
• Add some more dissolving solvent
• Filter (if all else fails!)

The Crystallization:

• Use clean container and clear solution (particles will affect crystal growth).
• You can control the rate of evaporation by:
  • Covering the container with little cotton
  • Covering with parafilm or aluminium foil and making few small holes
  • In inert atmosphere, by changing the rate of flow of inert gas.
• Leave the crystallization in a place without much air/mechanical disturbance
• Place the container in a way that you can check without disturbing
• Disturbances will cause the crystals to grow with poor quality (with lot of defects)
• Check the solution regularly and if any crystals appear, separate them at right size.