Extraction and washing

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). 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). 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. Example extractions and washes are detailed below, with a note on relative densities.

1. An example wash. A reaction generates an organic product, recovered as a solid. The solid is dissolved in ethyl acetate, and transferred to a separatory funnel. Water (the washing solvent) is added, forming a separate phase under the ethyl acetate. With mixing and shaking the layers, any compounds (such as polar impurities) which are much more soluble in water than in ethyl acetate are mostly transferred into the aqueous layer. The aqueous layer can then be drained out, leaving behind the product compound in the ethyl acetate phase.

2. An example extraction. A reaction generates an organic product, recovered as a solid. The product is soluble, to some degree, in both water and dichloromethane. The solid is dissolved in water, transferred to a separatory funnel, and dichloromethane (the extraction solvent) is added, forming a separate phase under the aqueous phase. With mixing and shaking the layers, any compounds (such as polar impurities) which are much more soluble in water than in dichloromethane remain in the aqueous layer. The product will partially transfer into the dichloromethane layer, which can then be drained out, leaving behind the aqueous phase. In addition to containing water-soluble impurities, the aqueous phase likely still contains some of the product – the amount of product recovered can be increased by adding more dichloromethane, and repeating the extraction, as many times as are necessary. The dichloromethane phases can then be combined for subsequent work-up steps.

3. A note on densities. When using a separatory funnel, the exact sequence of operations depends on the relative densities of the liquid phases, and which phase the desired compound is dissolved in.

Consider the example wash, above. The organic phase contains the desired compound, and it is less dense than the aqueous phase, hence it forms the upper layer. The aqueous phase forms the lower layer. Since the compound is being washed with water, the aqueous phase is undesired, and can be drained out of the separatory funnel. If the procedure requires multiple water washes, fresh washing solvent can then be added to the sep funnel at this point; there is no need to pour the organic phase out through the neck, it can remain in the sep funnel for the next wash.

This would be different if the organic phase was more dense than water. In this case, the compound would be in the lower layer; the lower layer would be washed with water, then it would be drained out of the sep funnel and reserved. For multiple washes, the undesired aqueous layer would need to be poured out, then the organic phase reintroduced to the sep funnel, along with fresh water for the next wash.

4. Brine wash. A wash with saturated sodium chloride solution (also known as “brine”) is frequently conducted as one of the last stages in a work-up. This is because most organic solvents can dissolve at least a small amount of water within themselves, and this water is effectively an impurity. Washing the organic phase with water will obviously not help, and the small amount of water dissolved in the organic solvent does not form a separate phase. However, water has a high affinity for brine, so washing the organic phase with brine draws most of the water out from the organic phase, into an aqueous phase which can then be separated as normal. This is often conducted as one of the final steps in a work-up, since a subsequent wash with an aqueous phase would reintroduce the water to the organic phase.

The brine wash is a good way to remove the majority of residual water, but does not remove it entirely; drying agents (see below) are usually used to remove the last traces of water from an organic phase.