Inline liquid-liquid extraction

Liquid-liquid extraction is a purification technique that is used in work-up to separate compounds based on their relative solubilities in two immiscible solvents.

Inline liquid-liquid extraction

Liquid-liquid Extraction is a purification technique that is used in work-up to separate compounds based on their relative solubilities in two immiscible solvents.

In flow chemistry, work-up and subsequent separation of an organic and aqueous phase can be conducted by flowing the input stream across a hydrophobic membrane.

The separation of the phases is promoted by the cross-membrane pressure which forces the organic phase through the hydrophobic membrane. Both phases can then be fed into separate fluid lines which can go onto collection, waste or fed through for further reactions (multi-step synthesis).

The principles of liquid-liquid extraction in flow are based on the immiscibility of the organic and aqueous phases along with the fluid pressure. Both the overall system pressure and the cross membrane pressure (CMP) present in the separator section of the apparatus.

In flow, the liquid-liquid extraction apparatus allows the setting of both the system pressure and CMP. The apparatus consists of a separator which contains a hydrophobic PTFE membrane sandwiched between two halves of a separator chip.

A Syrris Asia Flow Liquid-Liquid Extractor (FLLEX) module allows for the work-up of flow reactions in-line of a flow experiment.

The combined organic and aqueous phases flow into the separator chip, where the CMP forces the organic phase through the hydrophobic membrane, and if required, to collection. The aqueous phase does not pass through the hydrophobic membrane and can also either be collected or discarded to waste.

A benefit of the ability to integrate the aqueous workup immediately after synthesis is the reduction of impurities that have occurred due to product degradation.

Once the phases come into contact, they will form alternate slugs in the contacting pipe and this is called “slug flow”. The internal diameter of the contactor section of the pipe is minimal and at this scale diffusion of molecules into the preferred slug occurs rapidly, speeding up the process of separation. The work-up stage of reactions can occur in-line in seconds as opposed to over several minutes.

Alongside this, liquid-liquid extraction in flow can separate two-phase mixtures that would be extremely difficult by typical techniques e.g. THF and an aqueous phase. As well as reducing the presence of emulsions containing impurities compared to analogous traditional separation techniques.

Once separation is complete both phases are then fed into separate fluid lines which can be fed into collection, waste or go into further reactions downstream depending on the nature of the desired reaction. This is ideal for the preparation of samples before sending directly to analysis, e.g. via a Sampler and Diluter.