Aqueous workup theory

Aqueous workup uses differences in solubility to extract or wash compounds. It is important to consider which solvent each compound would prefer to be in (i.e. which solvent the compound is more soluble in). The most important consideration is which layer the product is most soluble in.

As part of the workup, acidic and basic solutions can be used to chemically change the compounds, which may alter their solubility in different solvents. This depends on the presence of acidic and basic functional groups in the mixture of compounds present.

Example workup for the formation of an ester

This reaction involves the formation of an amide through the addition of the reagents to the flask, and stirring at room temperature for an hour. The reaction is then quenched with water.

After the reaction has stirred for an hour, water is added to quench the reaction. This will react with any unreacted benzoyl chloride, and form benzoic acid. 20 mL of ethyl acetate is then added to the reaction flask, and the mixture transferred to a separating funnel.

For each extraction and wash, the components in each layer should be considered.

First consider the components present from the reaction flask:

• Water - forms the aqueous layer

• Ethyl acetate - forms the organic layer

• THF - miscible with both water and ethyl acetate, so some will be in each layer

• Triethylamine - most soluble in the organic layer

• Benzyl benzoate (product) - most soluble in the organic layer

• Hydrochloric acid (by-product) - soluble in the aqueous layer

• Benzoic acid (formed from quench) - most soluble in the organic layer

• Benzyl alcohol (unreacted starting material) - this should be the limiting reagent and be entirely consumed, otherwise this will be isolated alongside the product

20 mL of 3M Hydrochloric acid is added to the flask before the first separation. This will protonate any triethylamine in the reaction and form a salt, which is more soluble in the aqueous layer.

The components in each layer should then be considered again:

• Water - forms the aqueous layer

• Ethyl acetate - forms the organic layer

• THF - miscible with both water and ethyl acetate, so some will be in each layer

• Triethylamine hydrochloride salt - most soluble in the aqueous layer

• Benzyl benzoate (product) - most soluble in the organic layer

• Hydrochloric acid - soluble in the aqueous layer

• Benzoic acid (formed from quench) - most soluble in the organic layer

• Benzyl alcohol (unreacted starting material) - this should be the limiting reagent and be entirely consumed, otherwise this will be isolated alongside the product

The aqueous layer can then be discarded, and 20 mL saturated sodium bicarbonate solution can be added to the separating funnel. This will deprotonate the benzoic acid, forming a salt, which is then more soluble in the aqueous layer. 

The components in each layer should then be considered again:

• Saturated sodium bicarbonate solution - forms the aqueous layer

• Ethyl acetate - forms the organic layer

• Benzyl benzoate (product) - most soluble in the organic layer

• Sodium salt of benzoic acid - most soluble in the aqueous layer

Once separated, the product will be isolated in the organic layer. It is generally a good idea to wash the organic layer with brine before the end of the workup. This is because some water will dissolve in the organic solvent and is effectively an impurity. Brine has a high affinity for water, so most of the water will move out of the organic layer and into the brine layer. However, some water may remain so it is a good idea to use a drying agent to remove the last traces of water.