Acid-base extraction
Encyclopedia
Acid-base extraction is a procedure using sequential liquid–liquid extractions to purify acid
s and bases
from mixtures based on their chemical properties.
Acid-base extraction is routinely performed during the work-up after chemical syntheses
and for the isolation of compounds and natural product
s like alkaloid
s from crude 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.
The addition of an acid to a mixture of an organic acid and base will result in the acid remaining uncharged, while the base will be protonated. If the organic acid, such as a carboxylic acid
, is sufficiently strong, 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 pKa
(or pKb) constants is large enough. Examples are:
Usually the pH is adjusted to a value roughly between the pKa (or pKb) constants of the compounds to be separated. Weak acids like citric acid
, phosphoric acid
, or diluted sulfuric acid
are used for moderately acidic pH values and hydrochloric acid
or more concentrated sulfuric acid is used for strongly acidic pH values. Similarly, weak bases like ammonia
or sodium bicarbonate
(NaHCO3) are used for moderately basic pH values while stronger bases like potassium carbonate
(K2CO3) or sodium hydroxide (NaOH) are used for strongly alkaline conditions.
or 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.
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
s and bases
Base (chemistry)
For the term in genetics, see base A base in chemistry is a substance that can accept hydrogen ions or more generally, donate electron pairs. A soluble base is referred to as an alkali if it contains and releases hydroxide ions quantitatively...
from mixtures based on their chemical properties.
Acid-base extraction is routinely performed during the work-up after chemical syntheses
Chemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
and for the isolation of compounds and natural product
Natural product
A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design...
s like alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
s from crude extract
Extract
An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol or water. Extracts may be sold as tinctures or in powder form....
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
The fundamental theory behind this technique is that salts, which are ionic, tend to be water-soluble while neutral molecules tend not to be.The addition of an acid to a mixture of an organic acid and base will result in the acid remaining uncharged, while the base will be protonated. If the organic acid, such as a carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
, is sufficiently strong, 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 pKa
Acid dissociation constant
An acid dissociation constant, Ka, is a quantitative measure of the strength of an acid in solution. It is the equilibrium constant for a chemical reaction known as dissociation in the context of acid-base reactions...
(or pKb) constants is large enough. Examples are:
- Very weak acids with phenolic OH groups like phenolPhenolPhenol, also known as carbolic acid, phenic acid, is an organic compound with the chemical formula C6H5OH. It is a white crystalline solid. The molecule consists of a phenyl , bonded to a hydroxyl group. It is produced on a large scale as a precursor to many materials and useful compounds...
, 2-naphthol2-Naphthol2-Naphthol, or β-naphthol, is a colorless crystalline solid with the formula C10H7OH. It is an isomer of 1-naphthol, differing by the location of the hydroxyl group on naphthalene. The naphthols are naphthalene homologues of phenol, with the hydroxyl group being more reactive than in the phenols....
, or 4-hydroxyindole (pKa around 10) from stronger acids like benzoic acidBenzoic acidBenzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...
or sorbic acidSorbic acidSorbic acid, or 2,4-hexadienoic acid, is a natural organic compound used as a food preservative. It has the chemical formula C6H8O2. It is a colourless solid that is slightly soluble in water and sublimes readily...
(pKa around 4–5) - Very weak bases like caffeineCaffeineCaffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
or 4-nitroaniline4-Nitroaniline4-Nitroaniline, p-nitroaniline or 1-amino-4-nitrobenzene is an organic compound with the formula C6H6N2O2. It is an organic chemical compound, consisting of a phenyl group attached to an amino group which is para to a nitro group. The chemical structure of p-nitroaniline is shown at the right...
(pKb around 13–14) from stronger bases like mescalineMescalineMescaline or 3,4,5-trimethoxyphenethylamine is a naturally occurring psychedelic alkaloid of the phenethylamine class used mainly as an entheogen....
or dimethyltryptamineDimethyltryptamineN,N-Dimethyltryptamine is a naturally occurring psychedelic compound of the tryptamine family. DMT is found in several plants, and also in trace amounts in humans and other mammals, where it is originally derived from the essential amino acid tryptophan, and ultimately produced by the enzyme INMT...
(pKb around 3–4)
Usually the pH is adjusted to a value roughly between the pKa (or pKb) constants of the compounds to be separated. Weak acids like citric acid
Citric acid
Citric acid is a weak organic acid. It is a natural preservative/conservative and is also used to add an acidic, or sour, taste to foods and soft drinks...
, phosphoric acid
Phosphoric acid
Phosphoric acid, also known as orthophosphoric acid or phosphoric acid, is a mineral acid having the chemical formula H3PO4. Orthophosphoric acid molecules can combine with themselves to form a variety of compounds which are also referred to as phosphoric acids, but in a more general way...
, or diluted sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
are used for moderately acidic pH values and hydrochloric acid
Hydrochloric acid
Hydrochloric acid is a solution of hydrogen chloride in water, that is a highly corrosive, strong mineral acid with many industrial uses. It is found naturally in gastric acid....
or more concentrated sulfuric acid is used for strongly acidic pH values. Similarly, weak bases like ammonia
Ammonia
Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
or sodium bicarbonate
Sodium bicarbonate
Sodium bicarbonate or sodium hydrogen carbonate is the chemical compound with the formula Na HCO3. Sodium bicarbonate is a white solid that is crystalline but often appears as a fine powder. It has a slightly salty, alkaline taste resembling that of washing soda . The natural mineral form is...
(NaHCO3) are used for moderately basic pH values while stronger bases like potassium carbonate
Potassium carbonate
Potassium carbonate is a white salt, soluble in water , which forms a strongly alkaline solution. It can be made as the product of potassium hydroxide's absorbent reaction with carbon dioxide. It is deliquescent, often appearing a damp or wet solid...
(K2CO3) or sodium hydroxide (NaOH) are used for strongly alkaline conditions.
Technique
Usually, the mixture is dissolved in a suitable solvent such as dichloromethaneDichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...
or diethyl ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
(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:- ZwitterionZwitterionIn chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...
s with acidic and basic functional groupFunctional groupIn organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
s in the same molecule, e.g. glycineGlycineGlycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
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. triphenylamineTriphenylamineTriphenylamine is an organic compound with formula 3N. In contrast to most amines, triphenylamine is nonbasic. Its derivatives have useful properties in electrical conductivity and electroluminescence, and they are used in OLEDs as hole-transporters....
and trihexylamine. - Very lipophilic acids that do not easily dissolve in the aqueous phase in their charged form, e.g. fatty acidFatty acidIn chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s. - Lower amines like ammoniaAmmoniaAmmonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
, methylamineMethylamineMethylamine is the organic compound with a formula of CH3NH2. This colourless gas is a derivative of ammonia, but with one H atom replaced by a methyl group. It is the simplest primary amine. It is sold as a solution in methanol, ethanol, THF, and water, or as the anhydrous gas in pressurized...
, or triethanolamineTriethanolamineTriethanolamine, often abbreviated as TEA, is an organic chemical compound which is both a tertiary amine and a triol. A triol is a molecule with three alcohol groups. Like other amines, triethanolamine is a strong base due to the lone pair of electrons on the nitrogen atom. Triethanolamine can...
which are miscible or significantly soluble in water at most pH. - Hydrophilic acids like acetic acidAcetic acidAcetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
, citric acidCitric acidCitric acid is a weak organic acid. It is a natural preservative/conservative and is also used to add an acidic, or sour, taste to foods and soft drinks...
, and most inorganic acids like sulfuric acidSulfuric acidSulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
or phosphoric acidPhosphoric acidPhosphoric acid, also known as orthophosphoric acid or phosphoric acid, is a mineral acid having the chemical formula H3PO4. Orthophosphoric acid molecules can combine with themselves to form a variety of compounds which are also referred to as phosphoric acids, but in a more general way...
.
Alternatives
Alternatives to acid-base extraction including:- filtering the mixture through a plug of silica gelSilica gelSilica gel is a granular, vitreous, porous form of silica made synthetically from sodium silicate. Despite its name, silica gel is a solid. It is a naturally occurring mineral that is purified and processed into either granular or beaded form...
or alumina — charged salts tend to remain strongly adsorbed to the silica gel or alumina - ion exchange chromatographyIon exchange chromatographyIon-exchange chromatography is a process that allows the separation of ions and polar molecules based on their charge. It can be used for almost any kind of charged molecule including large proteins, small nucleotides and amino acids. The solution to be injected is usually called a sample, and the...
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
- ChromatographyChromatographyChromatography is the collective term for a set of laboratory techniques for the separation of mixtures....
, a more powerful but more complex procedure to separate compounds - ExtractionExtraction (chemistry)Extraction in chemistry is a separation process consisting in the separation of a substance from a matrix. It may refer to Liquid-liquid extraction, and Solid phase extraction....
- Multiphasic liquidMultiphasic liquidA multiphasic liquid is a mixture consisting of more than two immiscible liquid phases. Biphasic mixtures consisting of two immiscible phases are very common and usually consist of an organic solvent and an aqueous phase...
- Separating funnel