Utility: Separation of solid or liquid compounds with significantly different solubility properties, particularly if one compound is acidic or basic. 
The Concept: Compounds in a mixture are separated by their differential solubility in two immiscible solvents (one is usually water). The differential solubility is often expressed quantitatively as a partition coefficient. The partition coefficient is simply an equilibrium constant describing how much of a compound will be in each of the two immiscible solvents used in the extraction process. Kp=Csolvent 1/Csolvent2

 
 
 
 
  Thought Experiments based on the concept:

•Consider the compound anthracene. Would you expect it to be more soluble in water or in ether?

•Consider NaCl. Would you expect it to be more soluble in water or in ether?

•Water and ether are immiscible solvents and so will form two layers in a container. If a mixture of anthracene and NaCl is shaken up in a mixture of water and ether what is predominantly found in the ether? What is predominantly found in the water?

•The solubility in water of compound A is 10g/100mL. The solubility in ether of compound A is 1g/100mL. What is the partition coefficient (Kether/water) for compound A?

•The solubility in water for compound B is 1g/100mL. The solubility in ether for compound B is 5g/100mL. What is the partition coefficient (Kether/water) for compound B?

•A mixture containing 0.5g compound A and 1g compound B (solubility properties described above) is dissolved in 50 mL ether. The ether solution is shaken with 100 mL water and the liquid mixture is allowed to settle into two layers. How much of each compound is found in the ether layer and how much of each compound is found in the water layer?

•Consider the following chemical equilibrium:

What is the position of this equilibrium? In other words, if aniline is added to water is it more likely to be protonated or not?
 
 

•Consider the following chemical equilibrium:

What is the position of this equilibrium? In other words, if aniline is added to acidic water is it more likely to be protonated or not?

•If a small sample of aniline is shaken with a mixture of ether and water at pH 10 in which solvent layer will most of the aniline be found?

•If a small sample of aniline is shaken with a mixture of ether and water at pH 2 what species will be found predominantly in the water layer?

•Consider a mixture of aniline and anthracene completely dissolved in ether. If the ether solution is shaken with an equal amount of water at pH 10 where will most of the anthracene be found? Where will most of the aniline be found?

•Consider a mixture of aniline and anthracene completely dissolved in ether. If the ether solution is shaken with an equal amount of water at pH 2 where will most of the anthracene be found? Describe the situation with the aniline. If the aqueous solution is separated from the ether layer and basified what will happen chemically?

•Consider the acid base equilibrium position (as above) for benzoic acid in acidic water and in basic water. What would be the predominant form of benzoic acid at pH 2 and what relative solubility in ether/water would you expect for this species? What would be the predominant form of benzoic acid at pH 10 and what relative solubility in ether/water would you expect for this species?

•Design a scheme to isolate in relatively pure form each of the individual components of a mixture containing benzoic acid, anthracene and aniline.
 
 

Conclusion based on thought experiments:Organic materials can often be separated from inorganic salts on the basis of their differential solubilities in water. Organic acids or bases can be converted to water soluble salts under appropriate pH conditions. Water soluble salts can easily be separated from neutral organic compounds with low water solubility.
 
 

Pertinent information:

Solvent density is a useful bit of information in determining which layer is which solvent. Alternatively, one can design a simple experiment to make such a determination.
 
 

It is extremely important to keep track of layers as you generate them and as you collect them. You must be able to accurately answer the questions: What is the solvent for that layer/solution? How did you generate that layer/solution? What properties would you expect for species that are predominantly soluble in this layer/solution as opposed to the other layer? What did you expect to happen when you added acid? Why did you expect that? What did you expect to happen when you added base? Why did you expect that?
 
 

Organic solvents, when shaken with water, normally dissolve a small amount of that water. It is often removed by adding an anhydrous salt to the solution to absorb the water as water of hydration. You should remember that term from general chemistry. This is normally referred to as drying. One cannot, however, dry an aqueous solution this way although someone will try.
 
 
The separatory funnel is the central piece of glassware in a liquid/liquid extraction. It allows for mixing of phases and drawing one separated phase from the bottom via a stopcock. In the photo, water containing CoCl2 (red) is on the bottom and ether containing N,N-dimethyl-4-nitrosoaniline (green) is on the top.
 
 
 

The Method:
  1. If the mixture to be separated is already dissolved in a solvent place the solution in a separatory funnel.
  2. Add a portion of the extracting solvent (immiscible with the solvent of the original solution) to the separatory funnel.
  3. With a stopper on the top of the separatory funnel invert the funnel while holding the stopper in place with your finger.
  4. Open the stopcock to vent any pressure that may have developed in the funnel.
  5. Close the stopcock and gently shake the separatory funnel stopping occasionally to vent. This increases the surface area of contact between the two solvent phases and accelerates the partitioning process. Vent the funnel once again.
  6. Place the funnel securely upright in a clamp or ring on a stand and allow the contents to settle and the phases to separate.
  7. Remove the stopper and drain the bottom layer from the funnel, then the top layer if the extraction is complete.
If the mixture to be separated is NOT already dissolved in a solvent then dissolve it completely in one (usually a moderately polar aprotic organic solvent like chloroform or ether) if possible. Then place the solution in the separatory funnel and proceed as above.
 
 

Example:
 
 
 
 
N,N-dimethyl-4-nitrosoaniline (green) and naphthalene (white) are to be separated by extraction.
N,N-dimethyl-4-nitrosoaniline and naphthalene are both dissolved in CH2Cl2. This solution is placed in a separatory funnel. To the funnel is added 3M aqueous HCl and the mixture is shaken. After standing the phases separate. What layer is on top? What species (be specific) is in that layer? What layer is on the bottom? What species is in that layer?