View source for Acid-base extraction

{{Acids and bases}} 
'''Acid-base extraction''' is a procedure using sequential [[Liquid–liquid extraction|liquid–liquid extraction]]s to purify [[Chemistry:Acid|acid]]s and [[Chemistry:Base|bases]] from mixtures based on their chemical properties.<ref name=Harwood-Moody-EOCPAP>{{cite book |author=Laurence M. Harwood, Christopher J. Moody |title=Experimental organic chemistry: Principles and Practice |edition=Illustrated |pages=[https://archive.org/details/experimentalorga00harw/page/118 118–22] |isbn=978-0-632-02017-1 |date=13 June 1989 |publisher=WileyBlackwell |url=https://archive.org/details/experimentalorga00harw/page/118 }}</ref>

Acid-base extraction is routinely performed during the [[Chemistry:Work-up|work-up]] after [[Chemistry:Chemical synthesis|chemical syntheses]] and for the isolation of compounds and [[Chemistry:Natural product|natural product]]s like [[Chemistry:Alkaloid|alkaloid]]s from crude [[Chemistry:Extract|extract]]s. The product is largely free of neutral and acidic or basic impurities. It is not possible to separate chemically similar acids or bases using this simple method.

== Theory ==
{{see|Acid-base reaction}}
[[File:AcidBaseExtraction-overview.svg|600px|thumb|Overview of an acid-base extraction]]

The fundamental theory behind this technique is that [[Chemistry:Salt|salts]], which are [[Physics:Ionic compound|ionic]], tend to be water-soluble while neutral molecules tend not to be.

The addition of an acid to a mixture of an organic base and acid will result in the acid remaining uncharged, while the base will be protonated to form a salt. If the organic acid, such as a [[Chemistry:Carboxylic acid|carboxylic acid]], is sufficiently weak, its self-ionization can be suppressed by the added acid.

Conversely, the addition of a base to a mixture of an organic acid and base will result in the base remaining uncharged, while the acid is deprotonated to give the corresponding salt. Once again, the self-ionization of a strong base is suppressed by the added base.

The acid-base extraction procedure can also be used to separate very weak acids from stronger acids and very weak bases from stronger bases, as long as the difference of their [[Chemistry:Acid dissociation constant|pK<sub>a</sub>]] (or pK<sub>b</sub>) constants is large enough. For example:
* Very weak acids with phenolic OH groups like [[Chemistry:Phenol|phenol]], 2-naphthol, or 4-hydroxyindole (pK<sub>a</sub> around 10) from stronger acids like [[Chemistry:Benzoic acid|benzoic acid]] or [[Chemistry:Sorbic acid|sorbic acid]] (pK<sub>a</sub> around 4–5)
* Very weak bases like [[Biology:Caffeine|caffeine]] or 4-nitroaniline (pK<sub>b</sub> around 13–14) from stronger bases like [[Biology:Mescaline|mescaline]] or dimethyltryptamine (pK<sub>b</sub> around 3–4)

Usually the pH is adjusted to a value roughly between the pK<sub>a</sub> (or pK<sub>b</sub>) constants of the compounds to be separated. Weak acids like [[Chemistry:Citric acid|citric acid]], [[Chemistry:Phosphoric acid|phosphoric acid]], or diluted [[Chemistry:Sulfuric acid|sulfuric acid]] are used for moderately acidic pH values, and [[Chemistry:Hydrochloric acid|hydrochloric acid]] or more concentrated sulfuric acid is used for strongly acidic pH values. Similarly, weak bases like [[Chemistry:Ammonia|ammonia]] or [[Chemistry:Sodium bicarbonate|sodium bicarbonate]] (NaHCO<sub>3</sub>) are used for moderately basic pH values while stronger bases like [[Chemistry:Potassium carbonate|potassium carbonate]] (K<sub>2</sub>CO<sub>3</sub>) or [[Chemistry:Sodium hydroxide|sodium hydroxide]] (NaOH) are used for strongly alkaline conditions.

== Technique ==
Usually, the mixture is dissolved in a suitable solvent such as [[Chemistry:Dichloromethane|dichloromethane]] or [[Chemistry:Diethyl ether|diethyl ether]] (ether), and poured into a separating funnel. An aqueous solution of the acid or base is added, and the pH of the aqueous phase is adjusted to bring the compound of interest into its required form. After shaking and allowing for phase separation, the phase containing the compound of interest is collected. The procedure is then repeated with this phase at the opposite pH range. The order of the step is not important and the process can be repeated to increase the separation. However, it is often convenient to have the compound dissolved in the organic phase after the last step, so that the evaporation of the solvent yields the product.

== Limitations ==
The procedure works only for acids and bases with a large difference in solubility between their charged and their uncharged form. The procedure does not work for:
* [[Physics:Zwitterion|Zwitterion]]s with acidic and basic [[Chemistry:Functional group|functional group]]s in the same molecule, e.g. [[Chemistry:Glycine|glycine]] which tend to be water-soluble at most pH.
* Very lipophilic amines that do not easily dissolve in the aqueous phase in their charged form, e.g. [[Chemistry:Triphenylamine|triphenylamine]] and trihexylamine.
* Very lipophilic acids that do not easily dissolve in the aqueous phase in their charged form, e.g. [[Chemistry:Fatty acid|fatty acid]]s.
* Lower amines like [[Chemistry:Ammonia|ammonia]], [[Chemistry:Methylamine|methylamine]], or [[Chemistry:Triethanolamine|triethanolamine]] which are miscible or significantly soluble in water at most pH.
* Hydrophilic acids like [[Chemistry:Acetic acid|acetic acid]], [[Chemistry:Citric acid|citric acid]], and most inorganic acids like [[Chemistry:Sulfuric acid|sulfuric acid]] or [[Chemistry:Phosphoric acid|phosphoric acid]].

== Alternatives ==
Alternatives to acid-base extraction including:
* filtering the mixture through a plug of [[Chemistry:Silica gel|silica gel]] or alumina — charged salts tend to remain strongly adsorbed to the silica gel or alumina
* ion exchange chromatography can separate acids, bases, or mixtures of strong and weak acids and bases by their varying affinities to the column medium at different pH.

== See also ==
* [[Physics:Chromatography|Chromatography]], a more powerful but more complex procedure to separate compounds
* [[Chemistry:Extraction|Extraction]]
* Multiphasic liquid
* Separating funnel

== References ==
{{Reflist}}

== External links ==
* [http://web.centre.edu/muzyka/organic/lab/24_extraction.htm Acid base extraction]

{{Separation processes}}

[[Category:Laboratory techniques]]
[[Category:Equilibrium chemistry]]

{{Sourceattribution|Acid-base extraction|1}}