Recrystallization

Recrystallization is the most common method for purifying solid organic compounds. It exploits differences in solubility at different temperatures: the compound dissolves in a hot solvent and crystallizes when cooled, while impurities remain in solution.

Solvent selection is the most critical step. The ideal solvent:

• Dissolves the compound when hot but not when cold.
• Dissolves impurities at all temperatures (or not at all — they are removed by hot filtration).
• Does not react with the compound.
• Has a boiling point below the compound’s melting point (to avoid oiling out).
• Evaporates easily from the crystals.

If no single solvent works, use a mixed solvent system: dissolve the compound in a good solvent (e.g., ethanol, acetone), then add a poor solvent (e.g., water, hexane) dropwise until the solution becomes slightly turbid, then reheat to clarify. Cooling then induces crystallization.

Protocol:

1. Place the crude solid in a round-bottom flask or Erlenmeyer flask.
2. Add the minimum volume of hot solvent to just dissolve the solid.
3. If insoluble impurities are present, perform a hot gravity filtration.
4. Allow the solution to cool slowly to room temperature, then place in an ice bath.
5. If no crystals form, seed the solution with a few crystals from a previous batch or scratch the flask wall with a glass rod.
6. Collect the crystals by vacuum filtration on a Büchner funnel.
7. Wash the crystals with cold solvent (to remove residual mother liquor).
8. Air-dry or vacuum-dry the crystals.

Yield and purity: recrystallization typically recovers 60–90% of the material, with the remainder lost to the mother liquor. Purity is assessed by melting point (sharp, within 1–2 °C of the literature value) and TLC (single spot).

Liquid-Liquid Extraction

Liquid-liquid extraction (LLE) transfers a solute from one liquid phase to another based on differential solubility. It is the standard workup method for removing byproducts, unreacted starting materials, and inorganic salts from an organic reaction mixture.

Partition coefficient (K = concentration in organic phase / concentration in aqueous phase) determines how efficiently a compound can be extracted. Multiple small extractions are more efficient than one large extraction (three extractions with 1/3 volume each removes more solute than one extraction with full volume).

Typical workup:

1. Transfer the reaction mixture to a separatory funnel.
2. Add an immiscible solvent (typically diethyl ether, ethyl acetate, or DCM).
3. Shake gently with occasional venting (point the funnel away from people).
4. Allow the layers to separate completely.
5. Drain the lower layer and collect the upper layer.
6. Repeat the extraction 2–3 times.
7. Combine the organic layers and wash with brine (saturated NaCl) to remove residual water.
8. Dry over anhydrous Na₂SO₄ or MgSO₄, filter, and evaporate.

Acid-base extraction: a refinement that separates acidic, basic, and neutral compounds. Extract the organic layer with dilute HCl to protonate and remove basic compounds (they partition into the aqueous phase), then with dilute NaOH or NaHCO₃ to deprotonate and remove acidic compounds. Neutral compounds remain in the organic layer throughout.