Purification

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A Perfect Reaction (see all): A purification step would not be required. Perfect World Requiring Purification:

• Crystallization: Compound crystallizes spontaneously from solution.
• Distillation: Conditions for distillation are known and accurate, and your vacuum source is reliable.
• Column chromatography: Your compound quickly comes off a short silica column in a few pure fractions.

A Nightmare Scenario (see all): Your compound is an oil. No purification method has been reported for its isolation. The crude reaction mixture has three or four isomeric components, all with similar boiling points and Rf values.

Common Rookie Mistakes: Chromatography Distillation

Step by Step (time-sensitive):

1. Consult the literature. If conditions for successful purification of the compound have been reported, (Crystallization, Distillation, or Chromatography), follow the protocol!
2. If literature is unhelpful, you must choose a purification method for your compound

   Rules of Thumb (see all):

   • When you expect less than a gram of product, Chromatography is the safest purification method.
   • When the molecular weight of your compound is over 350 amu, beware of Distillation.
   • If your product is a solid and you have multigram quantities, consider Crystallization.
   • If you are working on multigram scale and the compound is an oil with molecular weight <350, consider Distillation.
   • If you have < 50 mg of compound, see Microscale Methods.

   For all other situations, use Column Chromatography.

3. Save a small sample of the crude product mixture in a vial.
4. Carry out the purification (for specific details, see Crystallization, Distillation, or Chromatography.) Keep everything.
5. Collect major product components in tared flasks, and assign names to each component. For details, see Record-Keeping.
6. Compare the components (usually by TLC) with the crude sample in the vial, and with the crude NMR, if any, to ensure that you have isolated the compounds of interest.
7. Calculate the yield of each component, if the identity of the compounds is known.
8. If this is the First Time Through, proceed to Analysis III: Characterization.

Tips (see all):

• If a solid crashes out of solvent at any point, filter it and analyze the solid and the filtrate.
• Do not throw out any fraction from the reaction until you have NMR spectra of the compounds of interest.

See also: Rookie Mistakes, How to Improve Your Yield, First Time Through, Chromatography Notes, How to Purify by Distillation, How to Handle, How to Work on Small Scale, Reaction Checklist, Troubleshooting the Experiment