User:Rickyc2002/Acid–base extraction

Acid–base extraction is a subclass of liquid–liquid extractions and involves the separation of chemical species from other acidic or basic compounds. It is typically performed during the work-up step following a chemical synthesis to purify crude compounds and results in the product being largely free of acidic or basic impurities. A separatory funnel is generally used to perform an acid-base extraction.

Acid-base extractions utilizes the difference in solubility of a compound in their acid or base form to induce separation. Typically, the desired compound is changed into its charged acid or base form, which causes it to become soluble in aqueous solution and thus be extracted from the non-aqueous (organic) layer. Acid-base extraction is a simple alternative to more complex methods like chromatography. Note that it is not possible to chemically similar acids or bases using this simple method.

Background Theory

Acid-base extraction works on the fundamental principle that salts are ionic compounds which are water soluble, while neutral molecules are typically water insoluble.

Overview of acid-base extraction and separation of a mixture into its neutral, acidic, and basic components.

Consider a mixture of acid and base compounds. Adding aqueous acid will cause the acidic component to stay uncharged, while the basic component will be protonated to form a salt. The uncharged acid will remain dissolved in the organic layer, while the highly charged basic salt will migrate to the aqueous layer. As the acidic and basic components are now in two different layers, they are able to easily be separated.

Alternatively, adding aqueous base will cause the acidic component to be deprotonated to form a salt, while the the basic component will remain uncharged. In this case, the uncharged base will stay in the organic layer while the highly charged acidic salt will migrate to the aqueous layer.

If the organic acid component has a higher pK_a value (such as a carboxylic acid), adding additional acid can further improve separation by minimizing the self ionization of the organic acid. This limits the acids tendency to enter the aqueous layer. This is also applicable when aqueous base is added to an organic base with a low pK_b value.

Although acid-base extractions are typically used to separate acids from bases, they can be used to separate two acids or two bases from each other. However, the acids and bases must differ greatly in strength, e.g. one strong acid and one very weak acid. Therefore, the two acids must have a large pK_a (or pK_b) difference. For example, the following can be separated:

• Very weak acids like phenols (pK_a around 10) from stronger acids like carboxylic acids (pK_a around 4–5).
• Very weak bases (pK_b around 13–14) from stronger bases (pK_b around 3–4). This is frequently used in purifying soil to determine trace metal concentration.

Usually, the pH is adjusted to a value roughly between the pK_a (or pK_b) constants to allow the compounds to be separated. For separating acidic compounds, the mixture can be first washed with a weak base (e.g. sodium bicarbonate) to extract the weak acid, then washed with a strong base (e.g. sodium hydroxide) to extract the strong acid. For separating basic components, weak acids like dilute acetic acid can first be used, then more concentrated acid (e.g. hydrochloric acid or nitric acid) is used to create strongly acidic pH values.

Technique

Example of acid-base extraction of two components: acidic phenol, and basic phenylamine. The green layer in the separatory funnel indicates the organic layer, while the colourless layer indicates the aqueous layer.

The following procedural steps are typically used when performing an acid-base extraction on a mixture containing one acid and one base:

1. The mixture of compounds is dissolved in a suitable organic solvent, such as dichloromethane or diethyl ether.
2. The solution is added to a separatory funnel. If the desired compound is basic, the solution will be washed with aqueous acid (e.g. 5% HCl); if it is acidic, the solution is washed with aqueous base (e.g. 5% NaOH).
3. The fractions are then shaken and the two phases are separated. The separatory funnel must be vented frequently to alleviate pressure build-up, especially when containing aqueous solutions that evolve carbon dioxide gas upon neutralization (such as sodium bicarbonate).
4. The fraction containing the analyte of interest is then collected. Typically, this is the aqueous layer, as addition of acid or base has caused the compound to become charged and highly soluble in the aqueous layer. The identity of the aqueous layer depends critically the organic solvent's density. Organic solvents with a density greater than 1.00 g/mL (e.g. dichloromethane) cause the aqueous layer to float to the top, while solvents with a density lower than 1.00 g/mL (e.g. ether) cause the aqueous layer to sink to the bottom.
5. The collected fraction is added to the separatory funnel again, and steps 2-4 are repeated twice more to maximize the yield of the extraction. On the final rinse, a brine solution is used to drive any remaining water out of the organic layer.
6. If the organic layer collected contains no analytes of interest, it is discarded; otherwise, the solvent is dried over a suitable drying agent (e.g. anhydrous sodium sulfate), filtered, then evaporated under reduced pressure to yield the pure compound. If the aqueous layer contains the analyte of interest, it is adjusted to the opposite pH (e.g. basic to acidic). Steps 1-4 are repeated with this fraction using an aqueous solution of opposite pH (e.g. NaOH to HCl). Note that this circular procedure is performed since it is typically easier to remove organic solvent via rotary evaporation than aqueous solvent .

Troubleshooting

The following issues are commonly observed during acid-base extraction and typically have simple solutions:

• Only one layer is observed in the separatory funnel.
  • This is due to using an organic solvent with significant miscibility with water (e.g. acetonitrile).The organic solvent used must be water-insoluble, to observe phase separation and be able to perform an acid-base extraction.

• Three layers form in the separatory funnel.
  • Often this is a result of insufficient mixing, and light stirring will solve the issue.

• The boundary between the organic layer and aqueous layer is not observed.
  • Ice can be used to identify the boundary as it will float between the two layers.

• An emulsion forms and one layer is suspended in the other as tiny droplets.
  • This can be solved by using a glass stirring rod to gently "push" the tiny droplets into each other, eventually resulting in separation and causing the two layers to appear. Adding a small amount of brine solution can also be used to break up the emulsion; this process is termed "salting out". Emulsions can be prevented by mixing the solutions gently rather than vigorously.
• The relative positions of the aqueous/organic layers are unknown.
  • A small amount of water can be added to the separatory funnel. Whichever layer these droplets go into is identified as the aqueous layer.

Limitations

Acid base extraction is efficient at separating compounds with a large difference in solubility between their charged and their uncharged form. Therefore, this procedure will not work for:

• Zwitterions with acidic and basic functional groups in the same molecule.
  • For instance, glycine is soluble in water at most pH values and is therefore difficult to be extracted into organic media.
• Lipophilic compounds.
  • Compounds such as tetrabutylammonium salts or fatty acids do not easily dissolve in the aqueous phase in their charged form.
• Basic amines.
  • Amines like ammonia, methylamine, or triethanolamine are miscible or significantly soluble in water at most pH and cannot be extracted into organic media.
• Hydrophilic inorganic acids.
  • Acids like acetic acid are indefinitely miscible in water and have limited solubility in organic solvents.

Alternatives

Alternatives to acid–base extraction include:

• Filtering the mixture through a plug of silica gel or alumina — if the product is a charged salt, it will remain strongly adsorbed to the silica gel or alumina.
• Ion exchange chromatography can separate acids, bases, or mixtures of strong and weak acids and bases by their varying affinities to the column medium at different pH.
• Using column chromatography to separate the neutral compounds according to their ratio-of-fronts values.
• Gel electrophoresis, which separates large biomolecules based on their charge and size.