Racemic Mixture and Resolution of Racemic Mixture

In this article we will learn about what is Racemic mixture? and Resolution of racemic mixture.

Key words : Racemic Mixture, Enantiomer, Optical activity, Chirality.

A Racemic mixture or racemate is a combination of qual amount of enantiomers of chiral compound. The enantiomers are the type of isomers of chiral compound which are optical active, however racemic mixture is optically inactive. 

Table of Contents

1. Introduction
2. Properties of Racemic mixture
3. Methods of formation of Racemic Mixture
4. Methods of Resolution of Racemic Mixture
5. Conclusion

1. Introduction

In other words, the mixture of 50 % "(+)" Enantiomer and 50 % "(-)" Enantiomer is known as racemic mixture. The (+) Enantiomer is the one which rotates plane polarized light in clockwise direction. Whereas, (-) Enantiomer rotates plane polarized light in counterclockwise direction. Since the racemic mixture contains two enantiomers, it rotates plane polarized light in equal and opposite extent. Therefore net optical rotation will be zero. In other words the racemic mixture is optically inactive.

Figure 1 : Racemic mixture

For example;

If we combine 1 mole of (+)-Tartaric acid and 1 mole of (-)-Tartaric acid it will produce 2 moles of racemic mixture of Tartaric acid. 

Figure 2 : Racemic mixture of Tartaric acid

2. Properties of Racemic mixture

• A racemic mixture have similar physical properties like the component enantiomers.
• A racemic mixture is denoted by "(+/-)" prefix.
• A racemic mixture reacts in same way in chemical reaction as the pure enantiomers. provided that the reagent used must be achiral.

3. Methods of formation of Racemic Mixture

3.1 Mixing

This is manual method to produce racemic mixture. The enantiomers of given compound are mixed in equimolar quantities to prepare racemic mixture.

3.2 Chemical Synthesis

A Prochiral molecule is a molecule which is achiral but it can be converted in to chiral molecule in single step. If the prochiral molecule reacts with achiral molecule to produce racemic mixture. For example; reaction of benzaldehyde with sodium cyanide provides racemic mixture of cyanohydrin.

Figure 3 : Reaction of Benzaldehyde with NaCN

Nature produces pure enantiomers in plants and organisms. A chemical reaction for the synthesis of chiral compound may produces racemic mixture. The process of formation of racemic mixture is known as Racemization.  As stated above racemic mixture is optically inactive, but if the synthesized product consist of unequal amount isomers, then optical purity of given mixture can be calculated. 

Since the enantiomers have identical physical properties such as melting point, boiling point, solubility etc. their separation is difficult task. The separation of racemic mixture in to its component enantiomers is known as Resolution. 

4. Methods of Resolution of Racemic Mixture

4.1 Crystallization

The racemic mixture can be crystallized to form individual crystals of component enantiomers. These crystals can be separated to give respective enantiomers. 

This method is employed by Louis Pasteur for the resolution of (+/-) Tartaric acid. In this method crystallization of sodium ammonium tartarate was carried out below 27 degree. Here two distinctive types of crystals are formed due to (+) and (-) salts. These crystals are identified and separated by using microscope. Later the salts were converted in to respective tartaric acid enantiomers by hydrolysis. 

This method is not useful in many cases where each crystals consist of both the enantiomers. 

4.2 Derivatization

The racemic mixture can be subjected to derivatization reaction where the end product would be a diastereomer. The diastereomers have different physical and  properties, hence they can be separated by crystallization, boiling point or column chromatography.  

For example;

Suppose we have a racemic mixture of hypothetical carboxylic acid. This can be derivatized as amide functionality by using chiral amine compound. This would generate mixture diastereomers of amide compound. The synthesized chiral amide compound can be separated by crystallization or column chromatography. Finally , the isolated amide compounds can be subjected to hydrolysis to produce pure (+) and (-) isomers of given carboxylic acid. 

Figure 4: Resolution of Racemic Mixture

We have discussed Purification techniques and column chromatography methods for organic compounds in previous articles. Please see for more details. 

4.3 Chiral column chromatography

The enantiomers can be separated by chiral column chromatography which involves chiral stationary phase. By this method resolution of racemic mixture can be carried out to isolate pure enantiomers. In this method two enantiomers of racemic mixtures "feels" different environment due to chiral stationary phase. Chiral stationary phases prepared by using cellulose or cyclodextrin (a seven membered cyclic sugar molecule).

4.3 Kinetic Resolution

Enantiomers are capable to react with chiral catalyst or reagent with different rates. Based on this phenomenon, racemic mixture is subjected to react with chiral reagent or catalyst. This would results in reaction of one enantiomer with chiral catalyst to for adduct and other enantiomer will be unreacted. Hence one enantiomer can be separated. This process is known as kinetic resolution. 

Figure 5: Kinetic Resolution

Many biocatalysts and chiral reagents are available for the purpose of kinetic resolution of compounds which can be used based on the structure of racemic compounds. The reactions include enantioselective oxidation or reduction reactions.

For example;

Lipase are most common enzymes which are used for kinetic resolution of secondary alcohols due to enantioselective acetylation. 

Figure 6 : Kinetic Resolution of Alcohols

5. Conclusion

1. We have learned that Racemic mixture is an equimolar mixture of two enantiomers of chiral compound.
2. A Racemic mixture is optically inactive.
3. Racemic mixture have identical physical and chemical properties as the component enantiomers.
4. A process of separation of enantiomers from racemic mixture is known as Resolution of racemic mixture.
5. There are methods available for resolution of enantiomers such as; Crystallization, Derivatization, Chiral column chromatography and Kinetic resolution by using chiral catalysts or reagents.

That's all for this topic, see you in next blog with another concept.