Liquid–liquid extraction

Liquid liquid extraction consists in transferring one (or more) solute(s) contained in a feed solution to another immiscible liquid (solvent). The solvent that is enriched in solute(s) is called extract. The feed solution that is depleted in solute(s) is called raffinate.

Solvent extraction

Liquid–liquid extraction also known as solvent extraction and partitioning, is a method to separate compounds based on their relative solubilities in two different immiscible liquids, usually water and an organic solvent. It is an extraction of a substance from one liquid into another liquid phase. Liquid–liquid extraction is a basic technique in chemical laboratories, where it is performed using a separatory funnel. This type of process is commonly performed after a chemical reaction as part of the work-up.

The term partitioning is commonly used to refer to the underlying chemical and physical processes involved in liquid–liquid extraction but may be fully synonymous. The term solvent extraction can also refer to the separation of a substance from a mixture by preferentially dissolving that substance in a suitable solvent. In that case, a soluble compound is separated from an insoluble compound or a complex matrix.

Solvent extraction is used in nuclear reprocessing, ore processing, the production of fine organic compounds, the processing of perfumes, the production of vegetable oils and biodiesel, and other industries.

Liquid–liquid extraction is possible in non-aqueous systems: In a system consisting of a molten metal in contact with molten salts, metals can be extracted from one phase to the other. This is related to a mercury electrode where a metal can be reduced, the metal will often then dissolve in the mercury to form an amalgam that modifies its electrochemistry greatly. For example, it is possible for sodium cations to be reduced at a mercury cathode to form sodium amalgam, while at an inert electrode (such as platinum) the sodium cations are not reduced. Instead, water is reduced to hydrogen. A detergent or fine solid can be used to stabilize an emulsion, or third phase..

Measures of effectiveness

Distribution ratio

In solvent extraction, a distribution ratio is often quoted as a measure of how well-extracted a species is. The distribution ratio (D) is equal to the concentration of a solute in the organic phase divided by its concentration in the aqueous phase. Depending on the system, the distribution ratio can be a function of temperature, the concentration of chemical species in the system, and a large number of other parameters.

Note that D is related to the ΔG of the extraction process.

Sometimes, the distribution ratio is referred to as the partition coefficient, which is often expressed as the logarithm. Note that a distribution ratio for uranium and neptunium between two inorganic solids (zirconolite and perovskite) has been reported. In solvent extraction, two immiscible liquids are shaken together. The more polar solutes dissolve preferentially in the more polar solvent, and the less polar solutes in the less polar solvent. In this experiment, the nonpolar halogens preferentially dissolve in the nonpolar mineral oil.

Separation factors

The separation factor is one distribution ratio divided by another; it is a measure of the ability of the system to separate two solutes. For instance, if the distribution ratio for nickel (D_Ni) is 10 and the distribution ratio for silver (D_Ag) is 100, then the silver/nickel separation factor (SF_Ag/Ni) is equal to D_Ag/D_Ni = SF_Ag/Ni = 10.

Decontamination factor

This is used to express the ability of a process to remove a contaminant from a product. For instance, if a process is fed with a mixture of 1:9 cadmium to indium, and the product is a 1:99 mixture of cadmium and indium, then the decontamination factor (for the removal of cadmium) of the process is 0.11 / 0.01 = 11.

Slopes of graphs

The easy way to work out the extraction mechanism is to draw graphs and measure the slopes. If for an extraction system the D value is proportional to the square of the concentration of a reagent (Z) then the slope of the graph of log₁₀(D) against log₁₀([[Z]]) will be two.

Techniques

Batchwise single stage extractions

This is commonly used on the small scale in chemical labs. It is normal to use a separating funnel. For instance, if a chemist were to extract anisole from a mixture of water and 5% acetic acid using ether, then the anisole will enter the organic phase. The two phases would then be separated.

The acetic acid can then be scrubbed (removed) from the organic phase by shaking the organic extract with sodium bicarbonate. The acetic acid reacts with the sodium bicarbonate to form sodium acetate, carbon dioxide, and water.

Multistage countercurrent continuous processes

Coflore continuous countercurrent extractor

These are commonly used in industry for the processing of metals such as the lanthanides; because the separation factors between the lanthanides are so small many extraction stages are needed. In the multistage processes, the aqueous raffinate from one extraction unit is fed to the next unit as the aqueous feed, while the organic phase is moved in the opposite direction. Hence, in this way, even if the separation between two metals in each stage is small, the overall system can have a higher decontamination factor.

Multistage countercurrent arrays have been used for the separation of lanthanides. For the design of a good process, the distribution ratio should be not too high (>100) or too low (<0.1) in the extraction portion of the process. It is often the case that the process will have a section for scrubbing unwanted metals from the organic phase, and finally a stripping section to obtain the metal back from the organic phase.

Mixer-settlers

Battery of mixer-settlers counter currently interconnected. Each mixer-settler unit provides a single stage of extraction. A mixer settler consists of a first stage that mixes the phases together followed by a quiescent settling stage that allows the phases to separate by gravity.

In the multistage countercurrent process, multiple mixer settlers are installed with mixing and settling chambers located at alternating ends for each stage (since the outlet of the settling sections feed the inlets of the adjacent stage’s mixing sections). Mixer-settlers are used when a process requires longer residence times and when the solutions are easily separated by gravity. They require a large facility footprint, but do not require much headspace, and need limited remote maintenance capability for occasional replacement of mixing motors. (Colven, 1956; Davidson, 1957)

4 stage battery of mixer-settlers for counter-current extraction

Centrifugal extractors

Centrifugal extractors mix and separate in one unit. Two liquids will be intensively mixed between the spinning rotor and the stationary housing at speeds up to 6000 RPM. This develops great surfaces for an ideal mass transfer from the aqueous phase into the organic phase. At 200 – 2000 g both phases will be separated again. Centrifugal extractors minimize the solvent in the process, optimize the product load in the solvent and extract the aqueous phase completely. Counter current and cross current extractions are easily established.

Extraction without chemical change

Some solutes such as noble gases can be extracted from one phase to another without the need for a chemical reaction (see absorption). This is the simplest type of solvent extraction. When a solvent is extracted, two immiscible liquids are shaken together. The more polar solutes dissolve preferentially in the more polar solvent, and the less polar solutes in the less polar solvent. Some solutes that do not at first sight appear to undergo a reaction during the extraction process do not have distribution ratio that is independent of concentration. A classic example is the extraction of carboxylic acids (HA) into nonpolar media such as benzene. Here, it is often the case that the carboxylic acid will form a dimer in the organic layer so the distribution ratio will change as a function of the acid concentration (measured in either phase).

For this case, the extraction constant k is described by k = [[HA_organic]]²/[[HA_aqueous]]

Solvation mechanism

Using solvent extraction it is possible to extract uranium, plutonium, or thorium from acid solutions. One solvent used for this purpose is the organophosphate tri-n-butyl phosphate. The PUREX process that is commonly used in nuclear reprocessing uses a mixture of tri-n-butyl phosphate and an inert hydrocarbon (kerosene), the uranium(VI) are extracted from strong nitric acid and are back-extracted (stripped) using weak nitric acid. An organic soluble uranium complex [UO₂(TBP)₂(NO₃)₂] is formed, then the organic layer bearing the uranium is brought into contact with a dilute nitric acid solution; the equilibrium is shifted away from the organic soluble uranium complex and towards the free TBP and uranyl nitrate in dilute nitric acid. The plutonium(IV) forms a similar complex to the uranium(VI), but it is possible to strip the plutonium in more than one way; a reducing agent that converts the plutonium to the trivalent oxidation state can be added. This oxidation state does not form a stable complex with TBP and nitrate unless the nitrate concentration is very high (circa 10 mol/L nitrate is required in the aqueous phase). Another method is to simply use dilute nitric acid as a stripping agent for the plutonium. This PUREX chemistry is a classic example of a solvation extraction.

Here in this case D_U = k TBP²[[NO₃]]²

Ion exchange mechanism

Another extraction mechanism is known as the ion exchange mechanism. Here, when an ion is transferred from the aqueous phase to the organic phase, another ion is transferred in the other direction to maintain the charge balance. This additional ion is often a hydrogen ion; for ion exchange mechanisms, the distribution ratio is often a function of pH. An example of an ion exchange extraction would be the extraction of americium by a combination of terpyridine and a carboxylic acid in tert-butyl benzene. In this case

D_Am = k terpyridine¹carboxylic acid³H+⁻³

Another example is the extraction of zinc, cadmium, or lead by a dialkyl phosphinic acid (R₂PO₂H) into a nonpolar diluent such as an alkane. A non-polar diluent favours the formation of uncharged non-polar metal complexes.

Some extraction systems are able to extract metals by both the solvation and ion exchange mechanisms; an example of such a system is the americium (and lanthanide) extraction from nitric acid by a combination of 6,6'-bis-(5,6-dipentyl-1,2,4-triazin-3-yl)-2,2'-bipyridine and 2-bromohexanoic acid in tert-butyl benzene. At both high- and low-nitric acid concentrations, the metal distribution ratio is higher than it is for an intermediate nitric acid concentration.

Ion pair extraction

It is possible by careful choice of counterion to extract a metal. For instance, if the nitrate concentration is high, it is possible to extract americium as an anionic nitrate complex if the mixture contains a lipophilic quaternary ammonium salt.

An example that is more likely to be encountered by the 'average' chemist is the use of a phase transfer catalyst. This is a charged species that transfers another ion to the organic phase. The ion reacts and then forms another ion, which is then transferred back to the aqueous phase.

For instance, the 31.1 kJ mol⁻¹ is required to transfer an acetate anion into nitrobenzene, while the energy required to transfer a chloride anion from an aqueous phase to nitrobenzene is 43.8 kJ mol⁻¹. Hence, if the aqueous phase in a reaction is a solution of sodium acetate while the organic phase is a nitrobenzene solution of benzyl chloride, then, when a phase transfer catalyst, the acetate anions can be transferred from the aqueous layer where they react with the benzyl chloride to form benzyl acetate and a chloride anion. The chloride anion is then transferred to the aqueous phase. The transfer energies of the anions contribute to that given out by the reaction.

A 43.8 to 31.1 kJ mol⁻¹ = 12.7 kJ mol⁻¹ of additional energy is given out by the reaction when compared with energy if the reaction had been done in nitrobenzene using one equivalent weight of a tetraalkylammonium acetate.

Aqueous two-phase extraction

Aqueous two-phase extraction, also known as two-phase liquid extraction, is a unique form of solvent extraction. In an aqueous two-phase extraction, compounds are still separated based on their solubility, but the two immiscible phases are both water-based, an aqueous two phase system.

Aqueous two-phase extractions can have a number of advantages over traditional solvent extraction. Solvents are often destructive to proteins, making the traditional extraction impossible for purifying proteins. In addition, organic solvents can be flammable, and their use can cause both environmental and health concerns. Aqueous-two phase extractions do not require solvents, and so avoid these concerns.

Types of aqueous two-phase extractions

Polymer–polymer systems. In a Polymer–polymer system, both phases are generated by a dissolved polymer. The heavy phase will generally be Polyethylene glycol (PEG), and the light phase is generally a polysaccharide. Traditionally, the polymer used is dextran. However, dextran is relatively expensive, and research has been exploring using less expensive polysaccharides to generate the light phase. If the target compound being separated is a protein or enzyme, it is possible to incorporate a ligand to the target into one of the polymer phases. This improves the target's affinity to that phase, and improves its ability to partition from one phase into the other. This, as well as the absence of solvents or other denaturing agents, makes polymer–polymer extractions an attractive option for purifying proteins. The two phases of a polymer–polymer system often have very similar densities, and very low surface tension between them. Because of this, demixing a polymer–polymer system is often much more difficult than demixing a solvent extraction. Methods to improve the demixing include centrifugation, and application of an electric field.

Polymer–salt systems. Aqueous two-phase systems can also be generated by introducing a high concentration of salt to a polymer solution. The polymer phase used is generally still PEG. Generally, a kosmotropic salt, such as Na₃PO₄ is used, however PEG–NaCl systems have been documented when the salt concentration is high enough. Since polymer–salt systems demix readily they are easier to use. However, at high salt concentrations, proteins generally either denature, or precipitate from solution. Thus, polymer–salt systems are not as useful for purifying proteins.

Ionic liquids systems. Ionic liquids are ionic compounds with low melting points. While they are not technically aqueous, recent research has experimented with using them in an extraction that does not use organic solvents.

Applications

• DNA purification: The ability to purify DNA from a sample is important for many modern biotechnology processes. However, samples often contain nucleases that degrade the target DNA before it can be purified. It has been shown that DNA fragments will partition into the light phase of a polymer–salt separation system. If ligands known to bind and deactivate nucleases are incorporated into the polymer phase, the nucleases will then partition into the heavy phase and be deactivated. Thus, this polymer–salt system is a useful tool for purifying DNA from a sample while simultaneously protecting it from nucleases.

• Food industry: The PEG–NaCl system has been shown to be effective at partitioning small molecules, such as peptides and nucleic acids. These compounds are often flavorants or odorants. The system could then be used by the food industry to isolate or eliminate particular flavors.

• Analytical chemistry: Often there are chemical species present or necessary at one stage of sample processing that will interfere with the analysis. For example, some air monitoring is performed by drawing air through a small glass tube filled with sorbent particles that have been coated with a chemical to stabilize or derivatize the analyte of interest. The coating may be of such a concentration or characteristics that it would damage the instrumentation or interfere with the analysis. If the sample can be extracted from the sorbent using a nonpolar solvent (such as toluene or carbon disulfide), and the coating is polar (such as HBr or phosphoric acid) the dissolved coating will partition into the aqueous phase. Clearly the reverse is true as well, using polar extraction solvent and a nonpolar solvent to partition a nonpolar interferent. A small aliquat of the organic phase (or in the latter case, (polar phase) can then be injected into the instrument for analysis.

• Purification of amines: Amines (analogously to ammonia) have a lone pair of electrons on the nitrogen atom that can for a relatively weak bond to a hydrogen atom. It is therefore the case that under acidic conditions amines are typically protonated, carrying a positive charge and under basic conditions they are typically deprotonated and neutral. Amines of sufficiently low molecular weight are rather polar and can form hydrogen bonds with water and therefore will readily dissolve in aqueous solutions. Deprotonated amines on the other hand, are neutral and have greasy, nonpolar organic substituents, and therefore have a higher affinity for nonpolar inorganic solvents. As such purification steps can be carried out where an aqueous solution of an amine is neutralized with a base such as sodium hydroxide, then shaken in a separatory funnel with a nonpolar solvent that is immiscible with water. The organic phase is then drained off. Subsequent processing can recover the amine by techniques such as recrystallization, evaporation or distillation; subsequent extraction back to a polar phase can be performed by adding HCl and shaking again in a separatory funnel (at which point the ammonium ion could be recovered by adding an insoluble counterion), or in either phase, reactions could be performed as part of a chemical synthesis.

Kinetics of extraction

It is important to investigate the rate at which the solute is transferred between the two phases, in some cases by an alteration of the contact time it is possible to alter the selectivity of the extraction. For instance, the extraction of palladium or nickel can be very slow because the rate of ligand exchange at these metal centers is much lower than the rates for iron or silver complexes.

Aqueous complexing agents

If a complexing agent is present in the aqueous phase then it can lower the distribution ratio. For instance, in the case of iodine being distributed between water and an inert organic solvent such as carbon tetrachloride then the presence of iodide in the aqueous phase can alter the extraction chemistry.

Instead of $D_{\mathrm {I} ^{+2}}$ being a constant it becomes $D_{\mathrm {I} ^{+2}}$ = k[[I₂._Organic]]/[I₂._Aqueous] [[I^-._Aqueous]]

This is because the iodine reacts with the iodide to form I₃^-. The I₃^- anion is an example of a polyhalide anion that is quite common.

Industrial process design

In a typical scenario, an industrial process will use an extraction step in which solutes are transferred from the aqueous phase to the organic phase; this is often followed by a scrubbing stage in which unwanted solutes are removed from the organic phase, then a stripping stage in which the wanted solutes are removed from the organic phase. The organic phase may then be treated to make it ready for use again.

After use, the organic phase may be subjected to a cleaning step to remove any degradation products; for instance, in PUREX plants, the used organic phase is washed with sodium carbonate solution to remove any dibutyl hydrogen phosphate or butyl dihydrogen phosphate that might be present.

Equipment

Phase separation during a laboratory scale LLE. The upper organic ether solution of MTBE is being extracted with the lower alkaline aqueous sodium bicarbonate solution to remove benzoic acid as the benzoate anion, leaving a non-acidic organic, benzil, (yellow in color) in the organic phase.

While solvent extraction is often done on a small scale by synthetic lab chemists using a separatory funnel, Craig apparatus or membrane-based techniques, it is normally done on the industrial scale using machines that bring the two liquid phases into contact with each other. Such machines include centrifugal contactors, Thin Layer Extraction, spray columns, pulsed columns, and mixer-settlers.

Extraction of metals

The extraction methods for a range of metals include:

• Cobalt – The extraction of cobalt from hydrochloric acid using alamine 336 in meta-xylene. Cobalt can be extracted also using Cyanex 272 {bis-(2,4,4-trimethylpentyl) phosphinic acid}.

• Copper – Copper can be extracted using hydroxyoximes as extractants, a recent paper describes an extractant that has a good selectivity for copper over cobalt and nickel.

• Neodymium – This rare earth is extracted by di(2-ethyl-hexyl)phosphoric acid into hexane by an ion exchange mechanism.

• Nickel – Nickel can be extracted using di(2-ethyl-hexyl)phosphoric acid and tributyl phosphate in a hydrocarbon diluent (Shellsol).

• Palladium and platinum – Dialkyl sulfides, tributyl phosphate and alkyl amines have been used for extracting these metals.

• Zinc and cadmium – The zinc and cadmium are both extracted by an ion exchange process, the N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) acts as a masking agent for the zinc and an extractant for the cadmium. In the modified Zincex process, zinc is separated from most divalent ions by solvent extraction. D2EHPA (Di (2) ethyl hexyl phosphoric acid) is used for this. A zinc ion replaces the proton from two D2EHPA molecules. To strip the zinc from the D2EHPA, sulfuric acid is used, at a concentration of above 170g/l (typically 240-265g/l).

References

• Sikdar, Cole, et al. Aqueous Two-Phase Extractions in Bioseparations: An Assessment. Biotechnology 9:254. 1991
• Szlag, Giuliano. A Low-Cost Aqueous Two Phase System for Enzyme Extraction. Biotechnology Techniques 2:4:277. 1988
• Dreyer, Kragl. Ionic Liquids for Aqueous Two-Phase Extraction and Stabilization of Enzymes. Biotechnology and Bioengineering. 99:6:1416. 2008
• Boland. Aqueous Two-Phase Systems: Methods and Protocols. Pg 259-269
• http://ull.chemistry.uakron.edu/chemsep/extraction/