Recrystallization

Recrystallization is the primary method for purifying solid organic compounds. The compound is dissolved in hot solvent, and the solution is allowed to cool slowly. Because solubility decreases with temperature, the compound crystallizes out of solution as the solvent cools. Impurities (present in smaller amounts) remain dissolved in the cold solvent and are removed by filtration.

The Principle

Solubility generally increases with temperature. For a compound with a steep temperature-solubility curve (solubility varies greatly between room temperature and boiling point of the solvent), recrystallization works well.

Protocol:

1. Dissolve the crude solid in a minimum volume of hot solvent. The solvent should boil at a temperature below the compound’s melting point.
2. If the solution has color from impurities, add decolorizing carbon (activated charcoal) and filter hot to remove the carbon + impurities.
3. Allow the solution to cool slowly to room temperature, then to ice-bath temperature (0°C) or colder.
4. Pure compound crystallizes out. Impurities (in smaller amount) stay dissolved in the cold solvent (the “mother liquor”).
5. Filter the crystals, wash with a small amount of cold solvent, and dry.

Choosing the Right Solvent

A good recrystallization solvent:

• Dissolves the compound well when hot but poorly when cold. Steep solubility-temperature curve.
• Does not react with the compound. No acid-sensitive substrate in acidic solvent, etc.
• Boils above the compound’s melting point minus ~30°C (so the compound dissolves fully in hot solvent without melting).
• Is volatile enough to evaporate from the crystals during drying.

Common recrystallization solvents: water, ethanol, methanol, ethyl acetate, hexane, acetone, benzene (though benzene is a carcinogen and less used now).

Mixed Solvents

If no single solvent has the right solubility profile, use a mixed solvent (two miscible solvents, one that dissolves the compound well and one that does not). Example:

1. Dissolve the compound in hot ethanol.
2. Add hot water carefully until the solution becomes slightly cloudy (compound starts to precipitate).
3. Heat gently until the cloudiness just clears.
4. Cool slowly.

The mixed solvent’s solubility curve can be tuned by adjusting the ratio.

Factors Affecting Crystal Quality

• Slow cooling gives larger, purer crystals. Fast cooling (sudden plunge into ice) gives smaller crystals and trapped impurities.
• Seed crystals (a tiny amount of the pure product added to the cooling solution) nucleate crystallization and ensure ordered crystal growth.
• Scratching the flask wall creates nucleation sites for reluctant systems.
• Adding a second solvent (anti-solvent) that reduces solubility can trigger crystallization in stubborn cases.

Theoretical Yield of Recrystallization

Yield is never 100% because some compound remains dissolved in the cold mother liquor. Typical yields: 60-80% after one recrystallization. Multiple recrystallizations further purify the crystals (at the cost of more losses).

Mother Liquor Recovery

The mother liquor still contains some of the desired compound. It can be concentrated (by evaporating solvent) and recrystallized again to recover more. Each subsequent crop is usually purer but smaller.