How to Purify by Crystallization

Submitted by Eric Chen

This method is best for reactions of >1g scale that produce a crude solid, and in which TLC analysis shows one major product. If significant amounts of impurities are visible by TLC, chromatography is recommended.

Sample a range of solvents with the goal of finding two solvents with the following characteristics: one solvent (“solvent a”) should not dissolve anything from the crude mixture, while the other solvent (solvent “b”) should sparingly solubilize the mixture upon heating. Solvent b should be more volatile than solvent a. Some sort of precipitation/cloudiness should result when adding a mixture of these two solvents to your crude product.
Solubilize your crude product in a flask or vial using a minimal amount of solvent b, gently heating if necessary. Add an appropriate amount of solvent a. Gently heat again if necessary and make sure everything is in solution. Adjust the proportion of solvents accordingly.
Cover the flask or vial with parafilm/wax/aluminum foil. Poke holes to allow SLOW evaporation of solvent b. Leave the vessel overnight at a location with minimal disturbance. As solvent b slowly evaporates, your solution will become more concentrated, and ideally the crude product will crash out as a pure crystalline solid. Some cooling can be used if nothing is precipitating at all.
If you get a precipitate, filter it and check the identity of both the solid and the mother liquor. You might have achieved partial purification, in which case you might accomplish complete purification by repeating the crystallization procedure.