View source for Liquid–liquid extraction

{{Short description|Method to separate compounds or metal complexes}}
{{Technical|date=August 2022}}
{{more citations needed section|date=June 2024}}

[[File:Funnels.jpg|thumb|upright=1.5|A [[separatory funnel]] used for liquid–liquid extraction, as evident by the two immiscible liquids.]]
'''Liquid–liquid extraction''', also known as '''solvent extraction''' and '''partitioning''', is a method to separate compounds or [[metal complex]]es, based on their relative [[solubility|solubilities]] in two different [[Miscibility|immiscible]] liquids, usually water (polar) and an organic solvent (non-polar). There is a net transfer of one or more [[Chemical species|species]] from one liquid into another liquid phase, generally from aqueous to organic. The transfer is driven by chemical potential, i.e. once the transfer is complete, the overall system of chemical components that make up the solutes and the solvents are in a more stable configuration (lower free energy). The solvent that is enriched in solute(s) is called extract. The feed solution that is depleted in solute(s) is called the [[raffinate]]. Liquid–liquid extraction is a basic technique in chemical laboratories, where it is performed using a variety of apparatus, from [[separatory funnels]] to [[countercurrent distribution]] equipment called as [[Mixer-settler|mixer settlers]].{{not verified in body|date=May 2014}} This type of process is commonly performed after a chemical reaction as part of the [[Work-up (chemistry)|work-up]], often including an acidic work-up.

The term ''partitioning'' is commonly used to refer to the underlying chemical and physical processes involved in ''liquid–liquid extraction'', but on another reading may be fully synonymous with it. 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.{{not verified in body|date=May 2014}}

From a [[Hydrometallurgy|hydrometallurgical]] perspective, solvent extraction is exclusively used in separation and purification of uranium and plutonium, zirconium and hafnium, separation of cobalt and nickel, separation and purification of rare earth elements etc., its greatest advantage being its ability to selectively separate out even very similar metals. One obtains high-purity single metal streams on 'stripping' out the metal value from the 'loaded' organic wherein one can precipitate or deposit the metal value. Stripping is the opposite of extraction: Transfer of mass from organic to aqueous phase.

Liquid–liquid extraction is also widely used in the production of fine [[organic compound]]s, the processing of [[perfume]]s, the production of [[vegetable fats and oils|vegetable oils]] and [[biodiesel]], and other industries.{{not verified in body|date=May 2014}} It is among the most common initial separation techniques, though some difficulties result in extracting out closely related functional groups.

Liquid-Liquid extraction can be substantially accelerated in [[microfluidic]] devices, reducing extraction and separation times from minutes/hours to mere seconds compared to conventional extractors.<ref>{{Cite journal | last1=Touma | first1=J. G. | last2=Coblyn | first2=M. | last3=Freiberg | first3=L. J. | last4=Kowall | first4=C. | last5=Zoebelein | first5=A. | last6=Jovanovic | first6=G. N. | title=Intensification of Solvent Extraction in an Additively Manufactured Microfluidic Separator | journal=Chemical Engineering Journal | volume=484 | year=2024 | pages=149285 | doi=10.1016/j.cej.2024.149285 | bibcode=2024ChEnJ.48449285T }}</ref>

Liquid–liquid extraction is possible in non-aqueous systems: In a system consisting of a molten metal in contact with [[molten salt]]s, metals can be extracted from one phase to the other. This is related to a [[mercury (element)|mercury]] [[electrode]] where a metal can be reduced, the metal will often then dissolve in the mercury to form an [[amalgam (chemistry)|amalgam]] that modifies its electrochemistry greatly. For example, it is possible for [[sodium]] [[cation]]s 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]].{{not verified in body|date=May 2014}}

==Measures of effectiveness==
{{more citations needed section|date=May 2014}}

===Distribution ratio===
In solvent extraction, a distribution ratio (D) is often quoted as a measure of how well-extracted a species is. The distribution ratio is a measure of the total  [[concentration]] of a [[solute]] in the organic phase divided by its concentration in the [[aqueous phase]].<ref name=":0">{{Cite web |date=2019-07-05 |title=7.7: Liquid-Liquid Extractions |url=https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Analytical_Chemistry_2.1_(Harvey)/07:_Obtaining_and_Preparing_Samples_for_Analysis/7.07:_Liquid-Liquid_Extractions |access-date=2024-09-16 |website=Chemistry LibreTexts |language=en}}</ref> The partition or distribution coefficient (K<sub>d</sub>) is the ration of solute concentration in each layer upon reaching equilibrium.<ref>{{Cite web |date=2017-10-21 |title=4.5: Extraction Theory |url=https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_Lab_Techniques_(Nichols)/04:_Extraction/4.05:_Extraction_Theory |access-date=2024-09-16 |website=Chemistry LibreTexts |language=en}}</ref>  This distinction between D and ''K<sub>d</sub>'' is important. The partition coefficient is a thermodynamic equilibrium constant and has a fixed value for the solute’s partitioning between the two phases. The distribution ratio’s value, however, changes with solution conditions if the relative amounts of ''A'' and ''B'' change. If we know the solute’s equilibrium reactions within each phase and between the two phases, we can derive an algebraic relationship between K<sub>d</sub> and ''D''. The partition coefficient and the distribution ratio are identical if the solute has only one chemical form in each phase; however, if the solute exists in more than one chemical form in either phase, then ''K<sub>d</sub>'' and ''D'' usually have different values.<ref name=":0" /> 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 Gibbs Free Energy (Δ''G)'' of the extraction process.<ref>{{Cite web |date=2016-09-09 |title=18.6: Gibbs Free Energy |url=https://chem.libretexts.org/Courses/University_of_Arkansas_Little_Rock/Chem_1403:_General_Chemistry_2/Text/18:_Entropy_and_Free_Energy/18.06:_Gibbs_Free_Energy |access-date=2024-09-16 |website=Chemistry LibreTexts |language=en}}</ref>

In solvent extraction, two immiscible liquids are shaken together.  The more [[Chemical polarity|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 non-polar mineral oil.<ref>{{cite web|url=http://people.rit.edu/lprsch/scha312ext_a.html|title=Solvent Extraction Notes|last=pnjjrose}}</ref>

===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<sub>Ni</sub>) is 10 and the distribution ratio for [[silver]] (D<sub>Ag</sub>) is 100, then the silver/nickel separation factor (SF<sub>Ag/Ni</sub>) is equal to D<sub>Ag</sub>/D<sub>Ni</sub> = SF<sub>Ag/Ni</sub> = 10.<ref>{{cite web|url=http://docslide.us/documents/basic-technology-and-tools-in-chemical-engineering-field-s-wesley.html|title=Basic Technology and Tools in Chemical Engineering Field - S. Wesley - Documents}}</ref>

===Measures of success===
Success of liquid–liquid extraction is measured through separation factors and decontamination factors. The best way to understand the success of an extraction column is through the liquid–liquid equilibrium (LLE) data set. The data set can then be converted into a curve to determine the steady state partitioning behavior of the solute between the two phases. The y-axis is the concentration of solute in the extract (solvent) phase, and the x-axis is the concentration of the solute in the raffinate phase. From here, one can determine steps for optimization of the process.<ref>{{cite web|url=http://modularprocess.com/wp-content/uploads/2015/07/Article-Liquid-LiquidExtraction-ChE-2004.pdf |title=Archived copy |access-date=2015-09-28 |archive-url=https://web.archive.org/web/20150929134303/http://modularprocess.com/wp-content/uploads/2015/07/Article-Liquid-LiquidExtraction-ChE-2004.pdf |archive-date=2015-09-29 }}</ref>

==Techniques==
{{more citations needed section|date=May 2014}}

===Batch wise single stage extractions===
This is commonly used on the small scale in chemical labs. It is normal to use a [[separating funnel]]. Processes include DLLME and direct organic extraction.<ref>{{Cite journal |last1=Mansour |first1=Fotouh R. |last2=Khairy |first2=Mostafa A. |date=2017-08-09 |title=Pharmaceutical and biomedical applications of dispersive liquid–liquid microextraction |url=https://linkinghub.elsevier.com/retrieve/pii/S1570023217306888 |journal=Journal of Chromatography B |language=en |volume=1061-1062 |pages=382–391 |doi=10.1016/j.jchromb.2017.07.055|pmid=28802218 |url-access=subscription }}</ref> After equilibration, the extract phase containing the desired solute is separated out for further processing.<ref>{{Cite book |last=Wilson |first=Ian D. |url=https://www.sciencedirect.com/referencework/9780122267703/encyclopedia-of-separation-science |title=Encyclopedia of Separation Science |publisher=[[Academic Press]] |year=2000 |isbn=978-0-12-226770-3 |pages=1371–1382 |language=en |chapter=EXTRACTION {{!}} Analytical Extractions |doi=10.1016/B0-12-226770-2/02271-7 |chapter-url=https://www.sciencedirect.com/science/article/abs/pii/B0122267702022717}}</ref>

====Dispersive liquid–liquid microextraction (DLLME)====
A process used to extract small amounts of organic compounds from water samples.<ref name="RezaeeAssadi2006">{{cite journal|last1=Rezaee|first1=Mohammad|last2=Assadi|first2=Yaghoub|last3=Milani Hosseini|first3=Mohammad-Reza|last4=Aghaee|first4=Elham|last5=Ahmadi|first5=Fardin|last6=Berijani|first6=Sana|title=Determination of organic compounds in water using dispersive liquid–liquid microextraction|journal=Journal of Chromatography A|volume=1116|issue=1–2|year=2006|pages=1–9|issn=0021-9673|doi=10.1016/j.chroma.2006.03.007|pmid=16574135}}</ref> This process is done by injecting small amounts of an appropriate extraction solvent (C<sub>2</sub>Cl<sub>4</sub>) and a disperser solvent (acetone) into the aqueous solution. The resulting solution is then [[centrifuge]]d to separate the organic and aqueous layers. This process is useful in extraction organic compounds such as organochloride and organophsophorus pesticides, as well as substituted benzene compounds from water samples.<ref name="RezaeeAssadi2006"/>

====Direct organic extraction====
By mixing partially organic soluble samples in organic solvent (toluene, benzene, xylene), the organic soluble compounds will dissolve into the solvent and can be separated using a [[separatory funnel]]. This process is valuable in the extraction of proteins and specifically phosphoprotein and phosphopeptide phosphatases.<ref name="Shacter1984">{{cite journal|last1=Shacter|first1=Emily|title=Organic extraction of Pi with isobutanol/toluene|journal=Analytical Biochemistry|volume=138|issue=2|year=1984|pages=416–420|issn=0003-2697|doi=10.1016/0003-2697(84)90831-5|pmid=6742419}}</ref>

Another example of this application is extracting [[anisole]] from a [[mixture]] of [[water]] and 5% [[acetic acid]] using [[diethyl ether|ether]], then the anisole will enter the organic phase. The two phases would then be separated.{{citation needed|date=May 2024}} 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.

[[Caffeine]] can also be extracted from coffee beans and tea leaves using a direct organic extraction. The beans or leaves can be soaked in ethyl acetate which favorably dissolves the caffeine, leaving a majority of the coffee or tea flavor remaining in the initial sample.<ref>{{cite web|author=Senese F |title=How is coffee decaffeinated? |publisher=General Chemistry Online |date=20 September 2005 |url=http://antoine.frostburg.edu/chem/senese/101/consumer/faq/decaffeinating-coffee.shtml |access-date=3 August 2009}}</ref>

===Multistage countercurrent continuous processes===
[[Image:Coflore ACX.png|thumb|Coflore continuous countercurrent extractor.]]

These are commonly used in [[Private industry|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.<ref name="Binnemans2007">{{cite journal|last1=Binnemans|first1=Koen|title=Lanthanides and Actinides in Ionic Liquids|journal=Chemical Reviews|volume=107|issue=6|year=2007|pages=2592–2614|issn=0009-2665|doi=10.1021/cr050979c|pmid=17518503|url=https://lirias.kuleuven.be/handle/123456789/58272|url-access=subscription}}</ref> 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 exchange|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 (chemistry)|stripping]] section to obtain the metal back from the organic phase.

====Mixer–settlers====
Battery of [[mixer-settler]]s 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.
[[File:Continuous_separation_of_oil&_water_mixture.jpg|thumb|Continuous separation of oil& water mixture
]]

A novel settling device, Sudhin BioSettler, can separate an oil-water emulsion continuously at a much faster rate than simple gravity settlers.  In this photo, an oil-water emulsion, stirred by an impeller in an external reservoir and pumped continuously into the two bottom side ports of BioSettler, is separated very quickly into a clear organic (mineral oil) layer exiting via the top of BioSettler and an aqueous (coloured with a red food dye) layer being pumped out continuously from the bottom of BioSettler.

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)<ref name="test">[http://www.cresp.org/NuclearChemCourse/monographs/11_Law_Liquid-liquid%20extraction%20equipment%20jdl_3_2_09.pdf Liquid–Liquid Extraction Equipment], Jack D. Law and Terry A. Todd, Idaho National Laboratory.</ref>
[[File:Mixer-settler-schema.jpg|thumb|4 stage battery of mixer-settlers for counter-current extraction.]]

====Centrifugal extractors====
[[Centrifugal extractor]]s 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.<ref>{{cite book |editor=James A. Kent |title=Riegel's Handbook of Industrial Chemistry |date=2003 |edition=10th |publisher=Springer |doi=10.1007/0-387-23816-6|isbn=978-0-306-47411-8 }}</ref>

===Extraction without chemical change===
Some solutes such as [[noble gas]]es can be extracted from one phase to another without the need for a chemical reaction (see [[Absorption (chemistry)|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'''<sub>organic</sub>]<sup>2</sup>/['''HA'''<sub>aqueous</sub>]

===Solvation mechanism===
{{unreferenced section|date=May 2014}}
Using solvent extraction it is possible to extract [[uranium]], [[plutonium]], [[thorium]] and many rare earth elements from acid solutions in a selective way by using the right choice of organic extracting solvent and diluent. One solvent used for this purpose is the [[organophosphate]] [[tributyl phosphate]] (TBP). The [[PUREX]] process that is commonly used in [[nuclear reprocessing]] uses a mixture of tri-n-butyl phosphate and an [[Chemically inert|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 (chemistry)|complex]] [UO<sub>2</sub>(TBP)<sub>2</sub>(NO<sub>3</sub>)<sub>2</sub>] is formed, then the organic layer bearing the uranium is brought into contact with a [[Concentration|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&nbsp;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]] [[wiktionary:Extraction|extraction]]. In this case, D<sub>U</sub> = k [TBP]<sup>2</sup>[NO<sub>3</sub><sup>−</sup>]<sup>2</sup>.

===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''<sub>Am</sub> = ''k'' [terpyridine]<sup>1</sup>[carboxylic acid]<sup>3</sup>[H<sup>+</sup>]<sup>−3</sup>

Another example is the extraction of [[zinc]], [[cadmium]], or [[lead]] by a di[[alkyl]] phosphinic acid (R<sub>2</sub>PO<sub>2</sub>H) into a nonpolar [[diluent]] such as an [[alkane]]. A non-[[Polar molecule|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-di[[pentyl]]-1,2,4-triazin-3-yl)-[[2,2'-bipyridine]] and 2-bromo[[hexanoic 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 [[kilojoule|kJ]] [[mole (unit)|mol]]<sup>−1</sup> is required to transfer an [[acetate]] anion into nitrobenzene,<ref>{{cite journal|last=Scholz|first=F.|author2=S. Komorsky-Lovric |author3=M. Lovric |date=February 2000|title=A new access to Gibbs energies of transfer of ions across liquid{{!}}liquid interfaces and a new method to study electrochemical processes at well-defined three-phase junctions|journal=Electrochemistry Communications|volume=2|issue=2|doi=10.1016/S1388-2481(99)00156-3|pages=112–118}}</ref> while  the energy required to transfer a chloride anion from an aqueous phase to nitrobenzene is 43.8 kJ mol<sup>−1</sup>.<ref>{{Cite journal |last1=de Namor |first1=Angela F. Danil |last2=Hill |first2=Tony |last3=Sigstad |first3=Elizabeth |date=1983 |title=Free energies of transfer of 1: 1 electrolytes from water to nitrobenzene. Partition of ions in the water + nitrobenzene system |url=http://xlink.rsc.org/?DOI=f19837902713 |journal=Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases |language=en |volume=79 |issue=11 |page=2713 |doi=10.1039/f19837902713 |issn=0300-9599|url-access=subscription }}</ref> 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<sup>−1</sup> = 12.7 kJ mol<sup>−1</sup> 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.<ref>{{cite web|url=http://ppsedu.com/en/index.php?page=39&parent=29|title=Extraction Operation|first=Dariush|last=zamani}}</ref>

====Types of aqueous two-phase extractions====
{{unreferenced section|date=March 2014}}
Polymer–polymer systems. In a Polymer–polymer system, both phases are generated by a dissolved polymer.  The heavy phase will generally be a [[polysaccharide]], and the light phase is generally [[Polyethylene glycol]] (PEG).  Traditionally, the polysaccharide used is [[dextran]].  However, dextran is relatively expensive, and research has been exploring using less expensive polysaccharides to generate the heavy 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 generating the heavy phase with a concentrated salt solution.  The polymer phase used is generally still PEG.  Generally, a [[kosmotropic]] salt, such as Na<sub>3</sub>PO<sub>4</sub> 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.

====DNA purification====
{{Main|DNA extraction}}
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.{{citation needed|date=October 2020}}

====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. [[Caffeine]] extraction used to be done using liquid–liquid extraction, specifically direct and indirect liquid–liquid extraction (Swiss Water Method), but has since moved towards super-critical CO<sub>2</sub> as it is cheaper and can be done on a commercial scale.<ref name="PekerSrinivasan1992">{{cite journal|last1=Peker|first1=Hulya|last2=Srinivasan|first2=M. P.|last3=Smith|first3=J. M.|last4=McCoy|first4=Ben J.|title=Caffeine extraction rates from coffee beans with supercritical carbon dioxide|journal=AIChE Journal|volume=38|issue=5|year=1992|pages=761–770|issn=0001-1541|doi=10.1002/aic.690380513|bibcode=1992AIChE..38..761P }}</ref><ref name="decaf 101">{{cite web|last1=Emden|first1=Lorenzo|title=Decaffeination 101: Four Ways to Decaffeinate Coffee|url=http://www.coffeeconfidential.org/health/decaffeination/|website=Coffee Confidential|date=6 July 2012 |access-date=29 October 2014}}</ref>

====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 aliquot of the organic phase (or in the latter case, polar phase) can then be injected into the instrument for analysis.

====Purification of amines====
[[Amine]]s (analogously to ammonia) have a lone pair of electrons on the nitrogen atom that can form 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.

===Temperature swing solvent extraction===
{{Main|Desalination#Temperature_swing_solvent_extraction}}

Temperature swing solvent extraction is an experimental technique for the desalination of drinking water. It has been used to remove up to 98.5% of the salt content in water, and is able to process hypersaline brines that cannot be desalinated using reverse osmosis.<ref>{{cite web|url=https://www.engineering.columbia.edu/press-releases/ngai-yin-yip-radical-desalination|title=Radical Desalination Approach May Disrupt the Water Industry|first=Holly|last=Evarts|date=6 May 2019 |publisher=Columbia Engineering|access-date=24 January 2021}}</ref>

==Kinetics of extraction==
{{unreferenced section|date=May 2014}}
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==
{{unreferenced section|date=May 2014}}
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 <math>D_{\mathrm{I}^{+2}}</math> being a constant it becomes

:<math>D_{\mathrm{I}^{+2}}</math> = ''k''[I<sub>2</sub> (organic)]/[I<sub>2</sub> (aq)][I<sup>−</sup> (aq)]

This is because the [[iodine]] reacts with the [[iodide]] to form [[Triiodide|I<sub>3</sub><sup>−</sup>]]. The I<sub>3</sub><sup>−</sup> 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.<ref>{{cite journal|last1=Reyes-Labarta|first1=J.A.|last2=Olaya|first2=M.M.|last3=Gómez|first3=A.|last4=Marcilla|first4=A.|title=New method for quaternary systems liquid-liquid extraction tray to tray design|journal=Industrial & Engineering Chemistry Research|date=1999|volume=38|issue=8|pages=3083–3095|doi=10.1021/ie9900723}}</ref><ref>{{cite journal|last1=Reyes-Labarta|first1=J.A.|last2=Grossmann|first2=I.E|title=Disjunctive Programming Models for the Optimal Design of Liquid-Liquid Multistage Extractors and Separation Sequences|journal=AIChE Journal|date=2001|volume=47|issue=10|pages=2243–2252|doi=10.1002/aic.690471011}}</ref>

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.

===Liquid-liquid equilibrium calculations===

In order to calculate the phase equilibrium, it is necessary to use a thermodynamic model such as NRTL, UNIQUAC, etc. The corresponding parameters of these models can be obtained from literature (e.g. Dechema Chemistry Data Series, [[Dortmund Data Bank]], etc.) or by a correlation process of experimental data.<ref>{{cite journal|last1=Reyes-Labarta|first1=J.A.|last2=Olaya|first2=M.M.|last3=Velasco|first3=R.|last4=Serrano|first4=M.D.|last5=Marcilla|first5=A.|title=Correlation of the Liquid-Liquid Equilibrium Data for Specific Ternary Systems with One or Two Partially Miscible Binary Subsystems|journal=Fluid Phase Equilibria|volume=278|issue=1–2|pages=9–14|doi=10.1016/j.fluid.2008.12.002|year=2009|bibcode=2009FlPEq.278....9R }}</ref><ref>{{cite journal|last1=Marcilla|first1=A.|last2=Reyes-Labarta|first2=J.A.|last3=Serrano|first3=M.D.|last4=Olaya|first4=M.M.|title=GE Models and Algorithms for Condensed Phase Equilibrium Data Regression in Ternary Systems: Limitations and Proposals|journal=The Open Thermodynamics Journal|date=2011|volume=5|pages=48–62|doi=10.2174/1874396X01105010048|doi-access=free|hdl=10045/19865|hdl-access=free}}</ref><ref>{{cite journal|last1=Marcilla|first1=Antonio|last2=Reyes-Labarta|first2=Juan A.|last3=Olaya|first3=M.Mar|title=Should we trust all the published LLE correlation parameters in phase equilibria? Necessity of their Assessment Prior to Publication|journal=Fluid Phase Equilibria|date=2017|volume=433|pages=243–252|doi=10.1016/j.fluid.2016.11.009|bibcode=2017FlPEq.433..243M |hdl=10045/66521|hdl-access=free}}</ref><ref>{{cite journal |last1=Labarta |first1=Juan A. |last2=Olaya |first2=Maria del Mar |last3=Marcilla |first3=Antonio |title=Graphical User Interface (GUI) for the analysis of Gibbs Energy surfaces, including LL tie-lines and Hessian matrix |website=University of Alicante |hdl=10045/51725 |hdl-access=free |url=http://rua.ua.es/dspace/handle/10045/51725 |date=2015-11-27}}</ref>

==Equipment==
[[File:Separation02.ogv|thumb|Phase separation during a laboratory scale liquid-liquid extraction. 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,<ref>{{cite journal|last1=Adamo|first1=Andrea|last2=Heider|first2=Patrick L.|last3=Weeranoppanant|first3=Nopphon|last4=Jensen|first4=Klavs F.|title=Membrane-Based, Liquid–Liquid Separator with Integrated Pressure Control|journal=Industrial & Engineering Chemistry Research|volume=52|issue=31|year=2013|pages=10802–10808|issn=0888-5885|doi=10.1021/ie401180t|hdl=1721.1/92770|url=https://dspace.mit.edu/bitstream/1721.1/92770/1/AA_PH_NW_KFJ_Separator_IECR.pdf|hdl-access=free}}</ref> 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 contactor]]s, [[Thin Layer Extraction]], [[spray column]]s, [[pulsed columns]], and [[mixer-settler]]s.

==Extraction of metals==
The extraction methods for a range of metals include:<ref>{{cite web|url=http://www.cognis.com/NR/rdonlyres/62A4BDA0-2B5F-4579-9761-968114B57A2A/0/thesolve.pdf |title=The Solvent Extraction of Some Major Metals |last=Mackenzie |first=Murdoch |publisher=Cognis GmbH |access-date=2008-11-18 |archive-url=https://web.archive.org/web/20100104224630/http://cognis.com/NR/rdonlyres/62A4BDA0-2B5F-4579-9761-968114B57A2A/0/thesolve.pdf |archive-date=2010-01-04 }}</ref><ref>{{Cite journal|last1=Patel|first1=Madhav|last2=Karamalidis|first2=Athanasios K.|date=May 2021|title=Germanium: A review of its US demand, uses, resources, chemistry, and separation technologies|journal=Separation and Purification Technology|volume=275 |language=en|page=118981|doi=10.1016/j.seppur.2021.118981 |issn=1383-5866|doi-access=free}}</ref>

=== Cerium ===
Ce(IV) can separated from other rare earth (III) ions by using sulfuric acid and HDEHP to produce high-purity cerium oxide.<ref name=":1">{{Cite book |last=Qi |first=Dezhi |title=Hydrometallurgy of Rare Earths: Extraction and Separation |date=2018 |publisher=Elsevier |isbn=978-0-12-813921-9 |edition=First |location=Cambridge, MA}}</ref>

===Cobalt===
The extraction of cobalt from [[hydrochloric acid]] using [[Alamine 336]] (tri-octyl/decyl amine) in ''[[Meta (prefix)|meta]]''-[[xylene]].<ref>{{cite journal|last1=Filiz|first1=M.|last2=Sayar|first2=N.A.|last3=Sayar|first3=A.A.|title=Extraction of cobalt(II) from aqueous hydrochloric acid solutions into Alamine 336–m-xylene mixtures|journal=Hydrometallurgy|volume=81|issue=3–4|year=2006|pages=167–173|issn=0304-386X|doi=10.1016/j.hydromet.2005.12.007|bibcode=2006HydMe..81..167F }}</ref> Cobalt can be extracted also using  [[dialkylphosphinic acid|Ionquest 290 or Cyanex 272 {''bis''-(2,4,4-trimethylpentyl) phosphinic acid}]].

===Copper===
Copper can be extracted using hydroxy[[oxime]]s as extractants, a recent paper describes an extractant that has a good selectivity for copper over [[cobalt]] and [[nickel]].<ref>{{cite journal|last1=Baba|first1=Yoshinari|last2=Iwakuma|first2=Minako|last3=Nagami|first3=Hideto|title=Extraction Mechanism for Copper(II) with 2-Hydroxy-4-n-octyloxybenzophenone Oxime|journal=Industrial & Engineering Chemistry Research|volume=41|issue=23|year=2002|pages=5835–5841|issn=0888-5885|doi=10.1021/ie0106736}}</ref>
<!-- *An excellent demonstration of copper solvent extraction by the University of Queensland Hydrometallurgy Group can be viewed at the following link: www.youtube.com/watch?v=Iph-z5QY2_8 -->
=== Gadolinium ===
The rare earth element Gadolinium can be extracted with ''n-''tributyl phosphate and nitric acid to yield over a kilogram of gadolinium oxide.<ref>{{Cite journal |last1=Weaver |first1=Boyd |last2=Kappelmann |first2=F. A. |last3=Topp |first3=A. C. |date=August 1953 |title=Quantity Separation of Rare Earths by Liquid—Liquid Extraction. I. The First Kilogram of Gadolinium Oxide 1 |url=https://pubs.acs.org/doi/abs/10.1021/ja01112a019 |journal=Journal of the American Chemical Society |language=en |volume=75 |issue=16 |pages=3943–3945 |doi=10.1021/ja01112a019 |bibcode=1953JAChS..75.3943W |issn=0002-7863|url-access=subscription }}</ref>

===Neodymium===
The rare earth element Neodymium is extracted by di(2-ethyl-hexyl)phosphoric acid into [[hexane]] by an ion exchange mechanism.<ref>{{cite journal|last1=Sanchez|first1=J.M.|title=Extraction of Neodymium(III) at Trace Level with Di(2-Ethyl-Hexyl)Phosphoric Acid in Hexane|last2=Hidalgo|first2=M.|last3=Salvadó|first3=V.|last4=Valiente|first4=M.|journal=Solvent Extraction and Ion Exchange|volume=17|issue=3|year=1999|pages=455–474|issn=0736-6299|doi=10.1080/07366299908934623}}</ref> Neodymium can also be separated from dysprosium through selective precipitation of dysprosium with Cyanex 272 when the HNO3 concentration was 0.001&nbsp;mol/L.<ref>{{Cite journal |last1=Sun |first1=Pan-Pan |last2=Kim |first2=Do-Hyeon |last3=Cho |first3=Sung-Yong |date=2018-03-15 |title=Separation of neodymium and dysprosium from nitrate solutions by solvent extraction with Cyanex272 |url=https://linkinghub.elsevier.com/retrieve/pii/S0892687517303254 |journal=Minerals Engineering |volume=118 |pages=9–15 |doi=10.1016/j.mineng.2017.12.018 |bibcode=2018MiEng.118....9S |issn=0892-6875|url-access=subscription }}</ref>

===Nickel===
Nickel can be extracted using di(2-ethyl-hexyl)phosphoric acid and [[tributyl phosphate]] in a hydrocarbon diluent (Shellsol).<ref>{{cite web | url = http://www.biomet.com.au/Extract/NiCoFS.htm | publisher = BioMetallurgical Pty Ltd | author = Lee W. John | title = A Potential Nickel / Cobalt Recovery Process | access-date = 2006-03-31 | archive-url = https://web.archive.org/web/20080926003054/http://www.biomet.com.au/Extract/NiCoFS.htm | archive-date = 2008-09-26 }}</ref>

===Palladium and platinum ===
Dialkyl sulfides, tributyl phosphate and alkyl amines have been used for extracting palladium and platinum.<ref>{{cite web|url=http://www.halwachs.de/solvent-extraction.htm|title=Precious Metals Refining By Solvent Extraction |publisher=Halwachs Edelmetallchemie und Verfahrenstechnik |access-date=2008-11-18}}</ref><ref>{{cite journal|last1=Giridhar|first1=P.|last2=Venkatesan|first2=K.A.|last3=Srinivasan|first3=T.G.|last4=Vasudeva Rao|first4=P.R.|title=Extraction of fission palladium by Aliquat 336 and electrochemical studies on direct recovery from ionic liquid phase|journal=Hydrometallurgy|volume=81|issue=1|year=2006|pages=30–39|issn=0304-386X|doi=10.1016/j.hydromet.2005.10.001|bibcode=2006HydMe..81...30G }}</ref>

===Polonium===
[[Polonium]] is produced in reactors from natural [[bismuth-209|<sup>209</sup>Bi]], bombarded with [[neutron]]s, creating <sup>210</sup>Bi, which then decays to <sup>210</sup>Po via beta-minus decay. The final purification is done pyrochemically with sodium hydroxide at {{degC|500}}. This is then followed by liquid-liquid extraction, with dibutyl Carbitol as the extractant.<ref>{{cite journal |title =Pyrochemical Extraction of Polonium from Irradiated Bismuth Metal |first =Wallace W. |last = Schulz |author2 = Schiefelbein, Gary F. |author3 = Bruns, Lester E. |journal = Ind. Eng. Chem. Process Des. Dev. |date = 1969 |volume = 8 |issue = 4 |pages= 508–515| doi = 10.1021/i260032a013}}</ref>

=== Thorium ===
Thorium can be extracted from other rare earths by using sulfuric acid and the extractant, N1923, to produce thorium oxide with 99.5% purity and 99% recovery.<ref name=":1" />

===Zinc and cadmium===
Zinc and cadmium are both extracted by an ion exchange process, the [[TPEN|''N,N,N′,N′''-tetrakis(2-pyridylmethyl)ethylenediamine]] (TPEN) acts as a masking agent for the zinc and an extractant for the cadmium.<ref>{{cite journal |author1=K. Takeshita |author2=K. Watanabe |author3=Y. Nakano |author4=M. Watanabe | title = Solvent extraction separation of Cd(II) and Zn(II) with the organophosphorus extractant D2EHPA and the aqueous nitrogen-donor ligand TPEN | journal = [[Hydrometallurgy]] | year = 2003 | volume = 70 |issue=1–3 | pages = 63–71 | doi=10.1016/s0304-386x(03)00046-x|bibcode=2003HydMe..70...63T }}</ref> 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).

=== Lithium ===
Lithium extraction is more popular due to the high demand of [[Lithium-ion battery|lithium-ion batteries]]. [[Tributyl phosphate|TBP (Tri-butyl phosphate)]] and {{chem2|FeCl3}} are mostly used to extract lithium from brine (with high Li/Mg ratio).<ref>{{Cite journal |last1=Wesselborg |first1=Tobias |last2=Virolainen |first2=Sami |last3=Sainio |first3=Tuomo |date=2021-06-01 |title=Recovery of lithium from leach solutions of battery waste using direct solvent extraction with TBP and FeCl3 |journal=Hydrometallurgy |language=en |volume=202 |page=105593 |doi=10.1016/j.hydromet.2021.105593 |bibcode=2021HydMe.20205593W |s2cid=233662976 |issn=0304-386X|doi-access=free }}</ref> Alternatively,  Cyanex 272 was also used to extract lithium. The mechanism of lithium extraction was found differently from other metals, such as cobalt, due to the weak coordinating bonding between lithium ions and extractants.<ref>{{Cite journal |last1=Lu |first1=Junnan |last2=Stevens |first2=Geoff W. |last3=Mumford |first3=Kathryn A. |date=2021-12-01 |title=Development of heterogeneous equilibrium model for lithium solvent extraction using organophosphinic acid |url=https://www.sciencedirect.com/science/article/pii/S1383586621010170 |journal=Separation and Purification Technology |language=en |volume=276 |page=119307 |doi=10.1016/j.seppur.2021.119307 |issn=1383-5866|url-access=subscription }}</ref>

== See also==
* [[Fragrance extraction]]
* [[Dortmund Data Bank]]
* [[Non-random two-liquid model]] - (NRTL model) LL Phase Equilibrium Calculation
* [[UNIQUAC]] - LL Phase Equilibrium Calculation

==References==
{{Reflist}}

==Further reading==
*B.L. Karger, 2014, "Separation and Purification: Single-stage versus multistage processes" and "Separation and Purification: Separations Based on Equilibrium", Encyclopædia Britannica, see [http://www.britannica.com/EBchecked/topic/108875/separation-and-purification/80486/Single-stage-versus-multistage-processes#toc80487] and [http://www.britannica.com/EBchecked/topic/108875/separation-and-purification/80483/Separations-based-on-equilibria], accessed 12 May 2014.
*Gunt Hamburg, 2014, "Thermal Process Engineering: liquid–liquid extraction and solid-liquid extraction", see [http://www.gunt.de/download/extraction_english.pdf], accessed 12 May 2014.
*G.W. Stevens, T.C., Lo, &  M. H. I. Baird, 2007, "Extraction, liquid–liquid", in Kirk-Othmer Encyclopedia of Chemical Technology, {{doi|10.1002/0471238961.120917211215.a01.pub2}}, accessed 12 May 2014.
*Colin Poole & Michael Cooke, 2000, "Extraction", in Encyclopedia of Separation Science, 10 Vols., {{ISBN|978-0-12-226770-3}}, see [http://store.elsevier.com/product.jsp?isbn=9780122267703&gdftrk=gdfV26763_a_7c349_a_7c883_a_7c9780122267703&mckv=dvgJdFEm_dc&pcrid=50347813032&gclid=COrKzo65pr4CFW4R7AodjhQA5Q], accessed 12 May 2014.
*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
*https://web.archive.org/web/20100702074135/http://ull.chemistry.uakron.edu/chemsep/extraction/
*[http://hdl.handle.net/10045/51725 Topological Analysis of the Gibbs Energy Function (Liquid-Liquid Equilibrium Correlation Data). Including a Thermodynamic Review and a Graphical User Interface (GUI) for Surfaces/Tie-lines/Hessian matrix analysis] - University of Alicante (Reyes-Labarta et al. 2015-18)

{{Separation processes}}
{{Chemical equilibria}}

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