3.3.3 Applying acid-base extraction

By manipulating the pH of the aqueous layer, the partitioning of a solute can be changed. For example, consider a mixture of caffeine (neutral) and procaine (basic) that you wish to separate. The caffeine, being neutral, does not form a salt that tends to be partitioned to an aqueous layer. The procaine, on the other hand, can form a quaternary ammonium salt, and this salt will partition into an aqueous phase if that phase is acidic; if the aqueous layer is basic, the procaine will be partitioned into the organic layer. A procedure to separate these common drugs is therefore:

1. White powder (caffeine+procaine) is added to CH$_{\textrm{2}}$Cl$_{\textrm{2}}$ in a separatory funnel.
2. Aqueous acid (such as 0.1 M H$_{\textrm{2}}$SO$_{\textrm{4}}$) is added.
   • The neutral caffeine is partitioned into the methylene chloride (bottom) layer.
   • The sulfate salt of procaine is partitioned into the aqueous (top) layer.
     

3. The bottom layer is drained; the methylene chloride can be evaporated to obtain nearly pure caffeine.
4. Another portion of methylene chloride is added to the separatory funnel, which still contains the aqueous acid and dissolved procaine.
5. Solid or aqueous base is added to the aqueous phase until that phase is basic. The procaine, converted to free base, is partitioned into the methylene chloride (bottom) layer.
6. The bottom layer is drained; the methylene chloride can be evaporated to obtain nearly pure procaine. However, procaine base will likely not crystallize.