Tautomerization is the type of structural isomerism in which the positions of atoms in a molecule can be changed by the transfer of a hydrogen atom or a proton. The molecule exhibiting the phenomenon can exist in two readily interconvertible different structures known as tautomers.
Tautomers have the same chemical formula but differ in their bond connectivity of hydrogen atoms, in particular. The term tautomerism is derived from the Greek words; ‘tauto’ means same and meros means parts. They are formed due to the 1,3 migration of hydrogen atoms within the same molecule. it is important to note that they have definite structures and can be separable. They also have different stabilities such that, one form is more stable than the other. In fact, their relative stabilities can be calculated from the bond energies of newly formed bonds.
There is a dynamic equilibrium established between two tautomers, which can be catalyzed by acids or bases because it involves the transfer of a proton. However, in some cases, it can be achieved without a catalyst. This process is called autoprotolysis.
Tautomerization is important in biology, chemistry, and pharmaceuticals, as it can affect the stability, reactivity, and biological activity of molecules.
Types of Tautomerization
- Keto-Enol tautomerization
- Imine-Enamine tautomerization
- Nitro-Aci tautomerization
- Nitroso-Oxime tautomerization
- Ring-Chain tautomerization (Annular tautomerism)
- Lactam-Lactim tautomerization
Keto-Enol Tautomerizatiom
It is one of the important and common types of tautomerization. This is shown by carbonyl compounds. For keto-enol tautomerization to occur, there must be at least one α-hydrogen present. Therefore, aldehydes and ketones with alpha hydrogen can show this interconversion.
Note that, benzaldehyde does not have alpha hydrogen and thus can not form tautomers.
Generally, the keto form is more stable than the enol form. This is due because the (C=O) bond being a much stronger bond than C-C. The equilibrium lies toward keto form. Note that, due to the instability enol are very hard to separate.
Since keto-enol tautomerism is a slow process, however, it can be catalyzed by using a small quantity of acid or base.
Acid-catalyzed(keto-enol) tautomerization
It involves the protonation of carbonyl oxygen and results in the formation of a carbocation intermediate. Then in the next step, carbocation loses α-hydrogen and forms enol. This is similar to E1 reactions.
Base-catalyzed (keto-enol) tautomerization
It is due to the electron-withdrawing effect of the carbonyl group. Because of this, α-hydrogen becomes weakly acidic, and hence base (OH–) attacks to form enol. The resulting enolate is stabilized by the resonance.
The common examples showing keto-enol tautomerization, are given below:
- Acetone
- Acetoacetic ester
- Acetyl acetone
- Acetophenone
- Cyclohexa-1,3,5-trione
Imine-Enamine tautomerization
Imines are more stable than enamine, that’s why equilibrium lies greatly toward imines. However, when there is no hydrogen atom attached to a nitrogen atom then enamine dominates.
Nitro-Aci tautomerism
Nitro compounds are in equilibrium with ‘Aci’ compounds (nitronic acids or azinic acids). The nitro form is more stable than the ‘Aci’ form because of resonance.
Nitroso-Oxime tautomerization
In nitroso compounds, the nitrogen atom has a single bond with oxygen and a double bond with the alkyl group. They also show tautomerism. In this type, nitroso form is converted to oxime and vice-versa.
Note that, oximes are generally more stable than nitroso compounds.
Ring chain tautomerization
This is a rare type of tautomerism. It occurs in sugars, spirooxathianes, and γ-monocarboxylic acids. The ring chain led to intramolecular rearrangement, which results in cyclization. The cyclic form is more stable than the ring form, so the equilibrium is shifted toward the cyclic form.
Lactam-Lactim tautomerism
Lactams are cyclic amides. They also show tautomerism.
For example, lactams are in equilibrium with lactims as shown below:
Key Takeaways
- Tautomerization is the intramolecular 1,3-migration of hydrogen atoms.
- It is a type of constitutional isomerism.
- Tautomers only differ in the position of a hydrogen atom.
- They are readily interconvertible.
- They exist in dynamic equilibrium form.
- Tautomers have different stabilities and are separable.
- Tautomers are definite structures.
- Keto-enol is a common type of tautomerization, shown by carbonyl compounds.
- Mostly keto form is more stable than the enol form.
Related resources
- Stereoisomerism: Types & their Examples
- Constitutional vs. Stereoisomers
- Structural isomers: Types and Examples
Concepts Berg
What are tautomers?
Tautomers are interconvertible structures that differ only in the position of a hydrogen atom. They are in a dynamic equilibrium state.
What are the requirements for tautomerization to happen?
- Compounds must be polar.
- There must be at least one α-hydrogen.
- An acid or base catalyst is also required for tautomerism.
Define constitutional isomers.
These are the molecules having the same molecular formula but different arrangements of atoms within a molecule. These are also known as structural isomers.
Why keto form is more stable than the enol form?
In most cases, the keto form is more stable than the enol form because the C=O bond is much stronger than C-C.
What is the difference between metamerism and tautomerism?
Metamerism is the type of structural isomerism having an unequal distribution of carbon atom on both sides of functional groups whereas, tautomerism involve the intramolecular 1,3-migration of a hydrogen atom.
Why enol form is more stable than the keto form in phenol?
In phenol, the enol form is more stable than the keto form because it has an aromatic character. It is stabilized by the resonance energy of benzene.
What is the effect of solvent on keto-enol tautomerism?
Polar protic solvents such as water, alcohols, weak acids, etc favor the keto-form because they can form hydrogen bonding with the carbonyl group of ketone, whereas non-polar solvents shift the equilibrium toward the enol form.
References
- 7th edition of March’s Advanced Organic Chemistry by Micheal B. Smith.
- 7th edition of Organic Chemistry by John McMurry.
