![Amino acid zwitterions](https://upload.wikimedia.org/wikipedia/commons/d/de/Amino_acid_zwitterions.svg)
Tautomers () are
structural isomer
In chemistry, a structural isomer (or constitutional isomer in the IUPAC nomenclature) of a chemical compound, compound is another compound whose molecule has the same number of atoms of each element, but with logically distinct chemical bond, b ...
s (constitutional isomers) of
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
s that readily interconvert.
[
] The
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hydrogen atom within the compound. The phenomenon of tautomerization is called tautomerism, also called desmotropism. Tautomerism is for example relevant to the behavior of amino acids and nucleic acids, two of the fundamental building blocks of life.
Care should be taken not to confuse tautomers with depictions of "contributing structures" in chemical
resonance
Resonance describes the phenomenon of increased amplitude that occurs when the frequency of an applied periodic force (or a Fourier component of it) is equal or close to a natural frequency of the system on which it acts. When an oscillatin ...
. Tautomers are distinct chemical species that can be distinguished by their differing atomic connectivities, molecular geometries, and physicochemical and spectroscopic properties,
whereas resonance forms are merely alternative
Lewis structure
Lewis structures, also known as Lewis dot formulas, Lewis dot structures, electron dot structures, or Lewis electron dot structures (LEDS), are diagrams that show the chemical bonding, bonding between atoms of a molecule, as well as the lone pairs ...
(
valence bond theory
In chemistry, valence bond (VB) theory is one of the two basic theories, along with molecular orbital (MO) theory, that were developed to use the methods of quantum mechanics to explain chemical bonding. It focuses on how the atomic orbitals of ...
) depictions of a single chemical species, whose true structure is best described as the "average" of the idealized, hypothetical geometries implied by these resonance forms.
Examples
![Acetylacetone keto-enol tautomerism](https://upload.wikimedia.org/wikipedia/commons/9/99/Acetylacetone_keto-enol_tautomerism.svg)
Tautomerization is pervasive in
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...
.
It is typically associated with polar molecules and ions containing functional groups that are at least weakly acidic. Most common tautomers exist in pairs, which means that the hydrogen is located at one of two positions, and even more specifically the most common form involves a hydrogen changing places with a double bond: H−X−Y=Z ⇌ X=Y−Z−H. Common tautomeric pairs include:[
* ]ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...
– enol
In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The te ...
: H−O−C=C ⇌ O=C−C−H, see keto–enol tautomerism
In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...
* enamine
An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates.
:
The word "enamine" is derived from the affix ''en''-, used as the suffix of alkene, and th ...
– imine
In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bo ...
: H−N−C=C ⇌ N=C−C−H
**cyanamide
Cyanamide is an organic compound with the chemical formula, formula carbon, Cnitrogen, N2hydrogen, H2. This white solid is widely used in agriculture and the production of pharmaceuticals and other organic compounds. It is also used as an alcoho ...
– carbodiimide
In organic chemistry, a carbodiimide (systematic IUPAC name: methanediimine) is a functional group with the formula RN=C=NR. They are exclusively synthetic. A well known carbodiimide is dicyclohexylcarbodiimide, which is used in peptide synthesis. ...
**guanidine
Guanidine is the compound with the formula HNC(NH2)2. It is a colourless solid that dissolves in polar solvents. It is a strong base that is used in the production of plastics and explosives. It is found in urine predominantly in patients experie ...
– guanidine – guanidine: With a central carbon surrounded by three nitrogens, a guanidine group allows this transform in three possible orientations
* amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
– imidic acid: H−N−C=O ⇌ N=C−O−H (e.g., the latter is encountered during nitrile
In organic chemistry, a nitrile is any organic compound that has a functional group. The prefix ''cyano-'' is used interchangeably with the term ''nitrile'' in industrial literature. Nitriles are found in many useful compounds, including met ...
hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
reactions)
**lactam
A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''.
Nomenclature
Greek prefixes in alphabetical order indicate ring size:
* α-Lactam (3-atom rings)
* β-Lacta ...
– lactim
A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words ''lactone'' + ''amide''.
Nomenclature
Greek prefixes in alphabetical order indicate ring size:
* α-Lactam (3-atom rings)
* β-Lacta ...
, a cyclic form of amide-imidic acid tautomerism in 2-pyridone and derived structures such as the nucleobase
Nucleobases, also known as ''nitrogenous bases'' or often simply ''bases'', are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic b ...
s guanine
Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is called ...
, thymine
Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nu ...
, and cytosine
Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an am ...
[
* imine – imine, e.g., during ]pyridoxal phosphate
Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent ac ...
catalyzed enzymatic
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. ...
reactions
**R1R2C(=NCHR3R4) ⇌ (R1R2CHN=)CR3R4
*nitro – ''aci''-nitro (nitronic acid): RR'HC–N+(=O)(O–) ⇌ RR'C=N+(O–)(OH)
* nitroso
In organic chemistry, nitroso refers to a functional group in which the nitric oxide () group is attached to an organic moiety (chemistry), moiety. As such, various nitroso groups can be categorized as ''C''-nitroso compounds (e.g., nitrosoalkane ...
– oxime
In organic chemistry, an oxime is a organic compound belonging to the imines, with the general formula , where R is an organic side-chain and R’ may be hydrogen, forming an aldoxime, or another organic group, forming a ketoxime. O-substituted ...
: H−C−N=O ⇌ C=N−O−H
* ketene
In organic chemistry, a ketene is an organic compound of the form , where R and R' are two arbitrary monovalent chemical groups (or two separate substitution sites in the same molecule). The name may also refer to the specific compound ethen ...
– ynol
In organic chemistry, an alkynol (shortened to ynol) is an alkyne with a hydroxyl group affixed to one of the two carbon atoms composing the triple bond (). The deprotonated anions of ynols are known as ''ynolates''. An ynol with hydroxyl gro ...
, which involves a triple bond: H−C=C=O ⇌ C≡C−O−H
* amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
– ammonium carboxylate, which applies to the building blocks of the proteins. This shifts the proton more than two atoms away, producing a zwitterion
In chemistry, a zwitterion ( ; ), also called an inner salt or dipolar ion, is a molecule that contains an equal number of positively- and negatively-charged functional groups.
: With amino acids, for example, in solution a chemical equilibrium wil ...
rather than shifting a double bond: H2N−CH2−COOH ⇌ H3N−CH2−CO
*phosphite
The general structure of a phosphite ester showing the lone pairs on the P
In organic chemistry, a phosphite ester or organophosphite usually refers to an organophosphorous compound with the formula P(OR)3. They can be considered as esters of a ...
– phosphonate
In organic chemistry, phosphonates or phosphonic acids are organophosphorus compounds containing groups (where R = alkyl, aryl, or just hydrogen). Phosphonic acids, typically handled as salts, are generally nonvolatile solids that are poorly ...
: P(OR)2(OH) ⇌ HP(OR)2(=O) between trivalent and pentavalent phosphorus.
Prototropy
Prototropy is the most common form of tautomerism and refers to the relocation of a hydrogen atom.[ Prototropic tautomerism may be considered a subset of acid-base behavior. Prototropic tautomers are sets of isomeric ]protonation
In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...
states with the same empirical formula
In chemistry, the empirical formula of a chemical compound is the simplest whole number ratio of atoms present in a compound. A simple example of this concept is that the empirical formula of sulfur monoxide, or SO, would simply be SO, as is th ...
and total charge
Charge or charged may refer to:
Arts, entertainment, and media Films
* '' Charge, Zero Emissions/Maximum Speed'', a 2011 documentary
Music
* ''Charge'' (David Ford album)
* ''Charge'' (Machel Montano album)
* ''Charge!!'', an album by The Aqu ...
. Tautomerizations are catalyzed
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
by:[
* bases, involving a series of steps: deprotonation, formation of a ]delocalized
In chemistry, delocalized electrons are electrons in a molecule, ion or solid metal that are not associated with a single atom or a covalent bond.IUPAC Gold Boo''delocalization''/ref>
The term delocalization is general and can have slightly dif ...
anion
An ion () is an atom or molecule with a net electrical charge.
The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...
(e.g., an enolate
In organic chemistry, enolates are organic anions derived from the deprotonation of carbonyl () compounds. Rarely isolated, they are widely used as reagents in the synthesis of organic compounds.
Bonding and structure
Enolate anions are electr ...
), and protonation
In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...
at a different position of the anion; and
* acid
In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
s, involving a series of steps: protonation, formation of a delocalized cation, and deprotonation at a different position adjacent to the cation).
Two specific further subcategories of tautomerizations:
*Annular tautomerism is a type of prototropic tautomerism wherein a proton can occupy two or more positions of the heterocyclic
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...
systems found in many drugs, for example, 1''H''- and 3''H''-imidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...
; 1''H''-, 2''H''- and 4''H''- 1,2,4-triazole; 1''H''- and 2''H''- isoindole
In organic chemistry and heterocyclic chemistry, isoindole consists of a benzene ring fused with pyrrole. The compound is an isomer of indole. Its reduced form is isoindoline. The parent isoindole is a rarely encountered in the technical liter ...
.
*Ring–chain tautomers occur when the movement of the proton is accompanied by a change from an open structure to a ring, such as the open chain
In chemistry, an open-chain compound (also spelled as open chain compound) or acyclic compound (Greek prefix "α", ''without'' and "κύκλος", ''cycle'') is a compound with a linear structure, rather than a cyclic one.
An open-chain compound h ...
and cyclic hemiacetal
A hemiacetal or a hemiketal has the general formula R1R2C(OH)OR, where R1 or R2 is hydrogen or an organic substituent. They generally result from the addition of an alcohol to an aldehyde or a ketone, although the latter are sometimes called hemike ...
(typically pyranose Pyranose is a collective term for saccharides that have a chemical structure that includes a six-membered ring consisting of five carbon atoms and one oxygen atom. There may be other carbons external to the ring. The name derives from its similarity ...
or furanose
A furanose is a collective term for carbohydrates that have a chemical structure that includes a five-membered ring system consisting of four carbon atoms and one oxygen atom. The name derives from its similarity to the oxygen heterocycle furan, bu ...
forms) of many sugars.[ (See .) The tautomeric shift can be described as H−O ⋅ C=O ⇌ O−C−O−H, where the "⋅" indicates the initial absence of a bond.
]
Valence tautomerism
Valence tautomerism is a type of tautomerism in which single and/or double bonds are rapidly formed and ruptured, without migration of atoms or groups. It is distinct from prototropic tautomerism, and involves processes with rapid reorganisation of bonding electrons.
A pair of valence tautomers with formula C6H6O are benzene oxide and oxepin
Oxepin is an oxygen-containing heterocycle consisting of a seven-membered ring with three double bonds. The parent C6H6O exists as an equilibrium mixture with benzene oxide. The oxepin–benzene oxide equilibrium is affected by the ring substi ...
.[
Other examples of this type of tautomerism can be found in ]bullvalene
Bullvalene is a hydrocarbon with the chemical formula . The molecule has a cage-like structure formed by the fusion of one cyclopropane and three cyclohepta-1,4-diene rings. Bullvalene is unusual as an organic molecule due to the and bonds fo ...
, and in open and closed forms of certain heterocycle
A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different chemical element, elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis ...
s, such as organic azide
In chemistry, azide is a linear, polyatomic anion with the formula and structure . It is the conjugate base of hydrazoic acid . Organic azides are organic compounds with the formula , containing the azide functional group. The dominant applic ...
s and tetrazole
Tetrazoles are a class of synthetic organic heterocyclic compound, consisting of a 5-member ring of four nitrogen atoms and one carbon atom. The name tetrazole also refers to the parent compound with formula CH2N4, of which three isomers can be f ...
s, or mesoionic
In chemistry, mesoionic compounds are one in which a heterocyclic structure is dipolar and where both the negative and the positive charges are delocalized. A completely uncharged structure cannot be written and mesoionic compounds cannot be rep ...
münchnone
Münchnone (synonyms: 1,3-oxazolium-5-oxide; 1,3-oxazolium-5-olate; anhydro-5-hydroxy-1,3-oxazolium hydroxide; 5-hydroxy-1,3-oxazolium hydroxide, inner salt; oxido-oxazolium) is a mesoionic heterocyclic aromatic chemical compound, with the molecula ...
and acylamino ketene.
Valence tautomerism requires a change in molecular geometry and should not be confused with canonical resonance structures
In chemistry, resonance, also called mesomerism, is a way of describing bonding in certain molecules or polyatomic ions by the combination of several contributing structures (or ''forms'', also variously known as ''resonance structures'' or '' ...
or mesomers.
Inorganic materials
In inorganic extended solids, valence tautomerism can manifest itself in the change of oxidation states its spatial distribution upon the change of macroscopic thermodynamic conditions. Such effects have been called charge ordering Charge ordering (CO) is a (first- or second-order) phase transition occurring mostly in strongly correlated materials such as transition metal oxides or organic conductors. Due to the strong interaction between electrons, charges are localized on ...
or valence mixing to describe the behavior in inorganic oxides.
Consequences for chemical databases
The existence of multiple possible tautomers for individual chemical substance
A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., wi ...
s can lead to confusion. For example, samples of 2-pyridone and 2-hydroxypyridine do not exist as separate isolatable materials: the two tautomeric forms are interconvertible and the proportion of each depends on factors such as temperature, solvent, and additional substituent
A substituent is one or a group of atoms that replaces (one or more) atoms, thereby becoming a moiety in the resultant (new) molecule. (In organic chemistry and biochemistry, the terms ''substituent'' and ''functional group'', as well as ''side ...
s attached to the main ring.[
:]
Historically, each form of the substance was entered into databases such as those maintained by the Chemical Abstracts Service
CAS (formerly Chemical Abstracts Service) is a division of the American Chemical Society. It is a source of chemical information. CAS is located in Columbus, Ohio, United States.
Print periodicals
''Chemical Abstracts'' is a periodical index tha ...
and given separate CAS Registry Number
A CAS Registry Number (also referred to as CAS RN or informally CAS Number) is a unique identification number assigned by the Chemical Abstracts Service (CAS), US to every chemical substance described in the open scientific literature. It inclu ...
s. 2-Pyridone was assigned 42-08-5
4 (four) is a number, numeral (linguistics), numeral and numerical digit, digit. It is the natural number following 3 and preceding 5. It is the smallest semiprime and composite number, and is tetraphobia, considered unlucky in many East Asian c ...
and 2-hydroxypyridine 09-10-4 The latter is now a "replaced" registry number so that look-up by either identifier reaches the same entry. The facility to automatically recognise such potential tautomerism and ensure that all tautomers are indexed together has been greatly facilitated by the creation of the International Chemical Identifier
The International Chemical Identifier (InChI or ) is a textual identifier for chemical substances, designed to provide a standard way to encode molecular information and to facilitate the search for such information in databases and on the we ...
(InChI) and associated software. Thus the standard InChI for either tautomer is
InChI=1S/C5H5NO/c7-5-3-1-2-4-6-5/h1-4H,(H,6,7)
.
See also
* Fluxional molecule
In chemistry and molecular physics, fluxional (or non-rigid) molecules are molecules that undergo dynamics such that some or all of their atoms interchange between symmetry-equivalent positions. Because virtually all molecules are fluxional in so ...
References
External links
*{{Commonscatinline, Tautomerism
Isomerism