Aqueous Workup
Extractions vs Washes
Extractions and washes are typical operations that are conducted as part of a reaction work-up. As techniques, they are very similar, and so the general term “extraction” is sometimes used to refer to both of them.
An extraction refers to “pulling out” a desired component (e.g. the product) from a mixture of components (e.g. the reaction mixture containing the product). This typically means the product moves from one layer into the other.
For example, a carboxylic acid is formed during a reaction, in it's salt form. This will result in the product being in the aqueous layer. Acid can be added to protonate the carboxylic acid, which will then cause it to be extracted into the organic layer when the two are shaken together.
Sometimes, sequential washes using the extraction solvent may be required to ensure all of the product transfers into the extraction solvent. This is especially the case when the product is partially soluble in both solvents.
A wash refers to “washing” undesired components (e.g. unreacted starting material) away from the desired material (e.g. the reaction mixture containing the product).
For example, washing an ethyl acetate (organic) layer containing the product with water (the washing solvent) will remove any compounds (such as polar impurities) which are more soluble in water than ethyl acetate out of the organic layer and into the water.
In each case, it is crucial to keep track of which layer is which, as the desired product may move from one layer to another. Disposing of the wrong layer is an unrecoverable mistake, so it is sensible to label each separated phase as it is generated, and retain them until the final product has been recovered.
Common extraction and washing solvents
Solvent
Density
What is it used for
Water
1.000 g cm-3
Often forms the aqueous layer, that polar compounds will extract into.
3M Hydrochloric acid in water
1.043 g cm-3
Can be used to protonate a compound or neutralise a base.
2M Sodium Hydroxide in water
1.087 g cm-3
Can be used to deprotonate a compound or neutralise an acid.
Saturated sodium bicarbonate solution in water
1.100 g cm-3
Can be used to deprotonate a compound or neutralise an acid.
Saturated sodium chloride solution (brine) in water
1.190 g cm-3
Brine is often used as a wash at the end of the workup to remove residual water from the organic layer. A certain amount of water will dissolve in organic solvents, and is effectively an impurity. Water has a high affinity for brine, so washing with brine will draw most of the water out of the organic phase and into the aqueous phase. This will not remove all of the water so a drying agent is also commonly used at the end of a workup.
Ethyl acetate
0.900 g cm-3
Often used as the organic layer to extract compounds into.
Dichloromethane (DCM)
1.325 g cm-3
Often used as the organic layer to extract compounds into, however it is more hazardous than ethyl acetate, so if the compound is soluble in ethyl acetate it is preferable to use it.
Ethanol
0.785 g cm-3
A solvent often used as a reaction solvent, however it is miscible with both water and organic solvents so it is not a good choice for aqueous workup. Some ethanol will go into both the aqueous and organic layers during an aqueous workup.
Diethyl ether
0.714 g cm-3
Can be used as the organic layer in an aqueous workup for extracting compounds into, however occasionally poor separation can be observed when using diethyl ether. The addition of a small amount of another solvent (such as ethyl acetate) may improve the separation.
Tetrahydrofuran (THF)
0.805 g cm-3
A solvent often used as a reaction solvent, however it is miscible with both water and organic solvents so it is not a good choice for aqueous workup. Some THF will go into both the aqueous and organic layers during an aqueous workup.