Epimers characteristics, formation and examples

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Jonah Lester

The epimers they are diastereoisomers in which only one of their achiral centers differs in spatial configuration; unlike enantiomers, where all the achiral centers have different configurations, and represent a pair of mirror images that cannot be superimposed on each other.

The rest of the diastereoisomers (geometric isomers, for example), can have more than two centers with different configurations. Hence, a large percentage of stereoisomers are diastereoisomers; while epimers are much less, but not for that reason, less important.

Source: Gabriel Bolívar

Suppose a structure with a skeleton of black atoms linked to the letters A, B, C and D (upper image). The dotted line represents the mirror, showing that the pair of molecules above are not enantiomers, since all their chiral centers have the same configuration; except, the first center, linked to the letters B and D.

The molecule on the left has the letter D facing the right side, while the molecule letter D on the right, faces the left side. To know what the configuration of each will be, use the Cahn-Ingold-Prelog system (R-S).

Article index

  • 1 Characteristics of epimers
  • 2 Training
    • 2.1 Tautomerization
  • 3 Examples
    • 3.1 Glucose anomers
    • 3.2 Isomers of menthol
  • 4 References

Characteristics of epimers

The main characteristic of epimers lies solely in an achiral (or stereogenic) center. Changing the spatial orientation of D and B can lead to more stable or unstable conformers; that is, the rotations of the single bonds cause two atoms or groups of bulky atoms to meet or move away.

From this perspective, one epimer can be much more stable than the other. The one that, by rotating its bonds, generates more stable structures, will be the epimer with the greatest tendency to form in equilibrium..

Going back to the letters, D and B can be very bulky, while C is a small atom. So, being so, the epimer on the right is more stable, since D and C found to the left of the first two centers suffer from less steric hindrance..

Microscopically this becomes a characteristic for the pair of epimers considered; but macroscopically, the differences are accentuated, and end up, for example, having different melting points, refractive indices, NMR spectra (in addition to many other properties).

But in the field of biology and enzyme-catalyzed reactions, this is where epimers differ even more; one could be metabolized by the body, while the other is not.

Training

How are epimers formed? Through a chemical reaction called epimerization. If both epimers do not differ greatly in stability, an epimerization equilibrium is established, which is nothing more than an interconversion:

EpA <=> EpB

Where EpA is epimer A, and EpB is epimer B. If one of them is much more stable than the other, it will have a higher concentration and will cause what is known as mutarotation; that is, it will be able to alter the direction of a polarized light beam.

Epimerization may not be equilibrium, and therefore irreversible. In these cases, a racemic mixture of EpA / EpB diastereoisomers is obtained..

The synthetic route of the epimers varies depending on the reagents involved, the reaction medium, and the process variables (use of catalysts, pressure, temperature, etc.).

For this reason the formation of each pair of epimers must be studied individually from the others; each with its own chemical mechanisms and systems.

Tautomerization

Out of all epimer formation processes, the tautomerization of two diastereoisomers can be considered as a general example..

This consists of an equilibrium where the molecule adopts a ketone (C = O) or enol (C-OH) form. Once the ketone form is reconverted, the configuration of the carbon adjacent to the carbonyl group (if chiral) changes, generating a pair of epimers.

An example of the above mentioned is the cis-decalone and trans-decalone pair.

Source: Jü [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], from Wikimedia Commons

The structure of cis-decalone is shown above. The H atoms are at the top of the two rings; while in the trans-decalone, one is above the rings, and the other is below. The carbon to the left of the C = O group is the chiral center, and therefore, the one that differentiates the epimers.

Examples

Glucose anomers

Source: miguelferig [Public domain], from Wikimedia Commons

The upper image shows the furan rings of the two anomers of D-glucose: α and β. From the rings it can be seen that the OH groups at carbon 1 are found either in the same direction as the adjacent OH, in the α anomer, or in opposite directions, as in the β anomer..

The Fisher projections of both anomers (on the right of the image) make the difference between the two epimers, which are themselves anomers, even clearer. However, two α anomers can have different spatial configurations on one of the other carbons, and therefore be epimers..

In the C-1 of the Fisher projection for the α anomer, the OH group “looks” to the right, while in the β anomer “looks” to the left.

Isomers of menthol

Source: Roland Mattern [Public domain], via Wikimedia Commons

In the image you have all the stereoisomers of the menthol molecule. Each column represents a pair of enantiomers (observe carefully), while the rows correspond to the diastereoisomers.

So what are epimers? They must be those that hardly differ in the spatial position of a single carbon..

(+) - menthol and (-) - neoisomenthol are epimers, and furthermore, diastereoisomers (they are not in the same column). If observed in detail, in both the -OH and -CH groups3 come out of the plane (above the ring), but in the (-) - neoisomenthol the isopropyl group also points out of the plane.

Not only (+) - menthol is epimeric of (-) - neoisomenthol, but also (+) - neomenthol. The latter differs only in that the group -CH3 points down the plane. Other epimers are:

-(-) - isomenthol and (-) - neomenthol

-(+) - isomenthol and (+) - neomenthol

-(+) - neoisomenthol and (-) - neomenthol

-(+) - neomenthol and (-) - neoisomenthol

These stereoisomers represent a practical example to clarify the concept of epimers, and you can see that, from several diastereoisomers, many can only differentiate into a single asymmetric or chiral carbon..

References

  1. Graham Solomons T.W., Craig B. Fryhle. (2011). Organic Chemistry. (10th edition.). Wiley plus.
  2. Carey F. (2008). Organic Chemistry. (Sixth edition). Mc Graw Hill.
  3. Uruguay Educa classrooms. (s.f.). Epimers. Recovered from: aulas.uruguayeduca.edu.uy
  4. Wikipedia. (2018). Epimer. Recovered from: en.wikipedia.org/wiki/Epimer
  5. Fray J. M. (2014). Investigation of Epimer Formation in Amide-Coupling Reactions: An Experiment for Advanced Undergraduate Students. School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, United Kingdom. J. Chem. Educ. 2014, 91, 1, 136-140
  6. Reist & col. (nineteen ninety five). Racemization, Enantiomerization, Diastereomerization and Epimerization: their Meaning and Pharmacological Significance. Chirality 7: 396-400.

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