Acid-Base Extraction

A widely employed method of separating organic compounds from mixtures in which they are found or produced is that of solvent-solvent extraction. Most reactions of organic compounds require extraction at some stage of product purification. In its simplest form, extraction results from the unequal distribution of a solute between two immiscible solvents. The distribution can be expressed quantitatively in terms of the distribution coefficient K, using the equation shown below for compound A distributed between an organic solvent and water.

If the solute is completely soluble in the organic solvent and completely insoluble in water, then K will have a value of infinity. This situation is never actually attained, but any value of K other than 1.0 indicates that the solute is more soluble in one of the two solvents. When choosing a solvent system for an extraction, some general principles should be kept in mind.

  1. The solvents must be immiscible.
  2. The solvents must have a favorable distribution coefficient for the component to be separated.
  3. The solvents must not react chemically with the components of the mixture, except in the cases of acid and base extraction, discussed below.
  4. The solvent must be readily removed from the solute following extraction.

Organic acids and bases can be separated from each other and from neutral compounds by extraction using aqueous solutions of different pH. Most organic acids (e.g., carboxylic acids) are insoluble or slightly soluble in water, but these compounds are highly soluble in dilute aqueous sodium hydroxide because the organic acid reacts with the base, as shown in equation 1.

RCO2H + NaOH RCO2 - Na+ (water soluble salt) + H2O (eq. 1)

Thus, the acid may be selectively removed from a mixture by dissolving the mixture in an organic solvent like dichloromethane (CH2Cl2) and then extracting the solution with dilute sodium hydroxide. The organic acid may be recovered from the aqueous solution by acidification (eq. 2), which causes precipitation, followed by filtration.

RCO2- Na+ + HCl RCO2H (s) + NaCl (eq. 2)

Likewise, organic bases that are insoluble in water may be separated by extraction with dilute hydrochloric acid. These bases (like amines) are soluble in acid due to the formation of a soluble salt, eq. 3.

RNH2 + HCl RNH3 + Cl- (water soluble salt) (eq. 3)

After the amine has been removed, it may be recovered from the aqueous solution by treatment with base, eq. 4.

RNH3+ Cl- + NaOH RNH2 (s) + NaCl (eq. 4)

Most macroscale extractions are carried out using separatory funnels. Microscale extractions, on the other hand, are conveniently performed with conical vials or centrifuge tubes using disposable pipettes to separate the liquid phases.

Experimental Procedure

Weigh out 0.2 grams of a solid mixture containing equal quantities of (1) benzoic acid (C6H5CO2H), (2) p-nitroaniline (NO2-C6H4NH2), and (3) naphthalene (C10H8). Dissolve the mixture in 2 mL of dichloromethane in your 5-mL conical vial, warming slightly on the hot plate if necessary.

Add 2 mL of 6 M NaOH, cap the vial, and shake it vigorously. Unscrew the cap slightly to vent (release the pressure that builds up) the vial. Allow the two phases to separate completely. (You should see two distinct layers.)

Using a disposable pipette, remove the lower organic layer and transfer it to a separate flask. Then remove the upper layer and save it in a container marked aqueous base extract. Put the organic layer back into your conical vial and repeat the extraction. Combine the two aqueous base layers and save them. You will recover the organic acid from this aqueous base extract.

Add 2 mL of 6 M HCl to the organic layer in the conical vial, carrying out an extraction like you did with the aqueous base. Put the aqueous acid in another flask and repeat the procedure with a second 2 mL of acid. Combine the two aqueous acid layers and save them to recover the organic base from this aqueous acid extract.

Add 1 mL of fresh dichloromethane to the organic layer in the conical vial. Remove any traces of water by adding a small amount of anhydrous sodium sulfate, swirling the mixture until the solution is no longer cloudy. Separate the liquid from the solid by means of a filter tip pipette. You should now have three separate solutions: (1) aqueous base extract containing organic acid, (2) aqueous acid extract containing organic base, and (3) organic solution containing neutral organic compound.

Cool the aqueous base extract in ice and then neutralize it by adding 6 M HCl gradually with stirring until it is just acidic with litmus paper. This neutralization will require 2-4 mL of HCl. An insoluble solid should be observed at this point. If you do not see a solid, you may need more HCl or you may need to cool your sample further. Isolate the solid by vacuum filtration using a Hirsch funnel, and wash the solid with a small amount of cold water. Let the solid dry in a sample vial overnight before determining its weight and melting point.

Repeat the above procedure on the aqueous acid extract using 6 M NaOH. After you isolate this solid, allow it to dry overnight in a labeled sample vial before obtaining its weight and melting point.

Evaporate the dichloromethane from the organic layer by boiling off the solvent on a hotplate in the hood. Note that dichloromethane boils at a very low temperature, so your hot plate only needs to be warm. When most of the liquid has evaporated, allow the sample to cool so that the organic neutral compound will crystallize. (Note that the neutral organic compound may melt and appear as a liquid on the hotplate.) Let the solid dry overnight in a sample vial before determining its weight and melting point.

Results:

  1. Include a flow chart to describe the separation of the mixture and the isolation of each component.
  2. Calculate the percent recovery of each component in the mixture. Assume that each component was present in equal amounts in your sample.
  3. Compare the melting points of each sample you isolated with their literature melting points (obtained from a CRC Handbook).
  4. Comment on the purity of each recovered component.
  5. How could the separation and recovery of the compounds separated be improved?

Questions:

  1. During an extraction, if you become uncertain about which layer is the organic layer, how could you determine it experimentally?
  2. From the results of this experiment, what can you conclude about the solubilities of each component in your mixture? Write specific chemical equations for each reaction that took place, using the skeletal structures of the molecules
  3. Should it make any difference if the mixture is extracted first with HCl or NaOH? Explain.
  4. Propose a method to separate a mixture containing phenol, benzoic acid, naphthalene, and p-nitroaniline. Phenol is soluble in sodium hydroxide solution but insoluble in neutral water or sodium bicarbonate solution. Benzoic acid is soluble in either sodium hydroxide or sodium bicarbonate solutions. Write out the structures of the molecules in your scheme.