Chemically-active extraction

Standard extractions use differences in solubility to extract, or wash, compounds. Chemically-active extraction is a common variant of extraction, which uses acidic solutions (such as dilute aqueous HCl) and basic solutions (such as aqueous sodium hydrogen carbonate solution) to make chemical changes to the compounds in the mixture, which dramatically alter their solubility in different solvents. This depends on the presence (and absence) of acidic and basic functional groups in the mixture of compounds.

In general terms, organic compounds are soluble in non-polar solvents. The presence of polar functional groups in an organic compound tends to make them more soluble in polar solvents; salts of organic compounds are generally soluble in water. So, if a neutral organic compound can be converted into a salt, in an easily-reversible reaction, then its solubility can be effectively changed from non-polar solvents to polar solvents. This principle underlies the technique of chemically-active extraction, also known as acid-base work-up.

Organic acids (e.g. containing a –COOH group) can be converted into their sodium salts by reaction with sodium hydrogen carbonate solution. Weaker organic acids (e.g. containing a phenolic –OH group) require a stronger base, such as sodium hydroxide solution. Organic bases (e.g. containing an –NH2 group) can be converted into a hydrochloride salt by reaction with dilute hydrochloric acid. Since these reagents are commonly used in extractions, they are usually present as premade solutions in the lab.

Three generic chemically-active extraction protocols are briefly described below, for the isolation of neutral, acidic, and basic organic compounds respectively. The protocols are also represented as flow-charts, for ease of visualisation. It is strongly recommended that you draw a similar flow-chart for your own work, if you are planning an extraction. Be aware that these are only generic protocols, and will not be applicable in every situation: specific choices regarding acid reagents, basic reagents, extraction solvents, volumes used, number of repetitions etc. will vary depending on the particular reaction. Ask a demonstrator if you are at all unsure. Also, particular care must be taken with the acidify/basify steps, as these are exothermic acid-base neutralisation reactions. Hot solutions should be always be allowed to cool before attempting an extraction.

1. Chemically-active extraction and purification of a neutral organic species

Starting with an organic solution of a neutral (i.e. without acidic or basic functional groups) organic species, potentially containing acidic impurities and basic impurities. The procedure involves extraction of the organic phase with dilute aqueous base; the aqueous layer then contains any acidic reaction impurities, and can be drawn off and set aside. The organic phase is then extracted with dilute aqueous acid; the aqueous layer then contains any basic reaction impurities, and can be drawn off and set aside. The organic phase is then washed with water, which removes traces of the acid wash, then washed with brine, to remove as much of the water as possible. This generates an organic solution of the neutral species, ready for subsequent steps (e.g. trace water removal, evaporation, etc.).

Choice of organic solvent is significant here. In general, it is most useful if the organic solvent is less dense than water (e.g. ether), so that it should form the upper layer in each extraction/wash; this means that, with each operation, the lower layer is aqueous, and can simply be drawn off and set aside. The organic phase can remain in the separatory funnel throughout, with fresh solutions being added through the neck as required.

Flow-chart for chemically-active extraction and purification of a neutral organic species

2. Chemically-active extraction and purification of an acidic organic species

Starting with an organic solution of an acidic organic species (e.g. with a –COOH group). The procedure begins with extraction of the organic solution with an aqueous base. The choice of aqueous base is important; it must be a sufficiently strong base to deprotonate the acidic functional group of the organic product species (see above). The base reacts with the organic acid, converting it into a water-soluble salt. Care must be taken here: this is an exothermic acid-base neutralisation reaction, which can raise the temperature of the solutions. Particular care must also be taken if aqueous sodium hydrogen carbonate is used as the base, since the neutralisation reaction generates CO2 gas. For these reasons, careful swirling of the two phases in the separatory funnel is appropriate, before shaking and mixing – see “use of a separatory funnel, 3a/3d”, above.

At this stage, the organic phase contains any neutral and/or basic organic impurities, and can be drawn off and set aside. The aqueous phase is basic, and contains the salt of the organic acid. This salt can be converted back into the neutral organic species by acidifying the solution with aqueous acid; this should be done with particular care, as it is an exothermic acid-base neutralisation reaction on a significant scale. The aqueous layer should be decanted into a conical flask, and the remaining base carefully neutralised by careful addition of aqueous HCl, until the solution is acid to litmus/pH paper. The solution should be cooled in an ice bath, if necessary, then reintroduced to the separatory funnel. An organic solvent is added. If any material remains in the conical flask, it can be rinsed into the sep funnel with organic solvent. The aqueous layer is then extracted with the organic solvent. This procedure, recovering the organic species from an aqueous layer, is sometimes called “back-extraction”.

The organic phase is then washed with water, which removes traces of acid, then washed with brine, to remove as much of the water as possible. This generates an organic solution of the neutral species, ready for subsequent steps (e.g. trace water removal, evaporation, etc.). 

Flow-chart for chemically-active extraction and purification of an acidic organic species

3. Chemically-active extraction and purification of a basic organic species

Starting with an organic solution of a basic organic species (e.g. with a –NH2 group). The procedure begins with extraction of the organic solution with an aqueous acid, typically dilute aqueous HCl. The acid reacts with the organic base, converting it into a water-soluble salt. Care must be taken here: this is an exothermic acid-base neutralisation reaction, which can raise the temperature of the solutions. For this reason, careful swirling of the two phases in the separatory funnel is appropriate, before shaking and mixing – see “use of a separatory funnel, 3a/3d”, above.

At this stage, the organic phase contains any neutral and/or acidic organic impurities, and can be drawn off and set aside. The aqueous phase is acidic, and contains the organic base, present as its HCl salt. The subsequent process is analagous to the previous protocol, except that the aqueous layer is “basified” to recover the neutral organic species

Flow-chart for chemically-active extraction and purification of a basic organic species