Racemic Mixture and its Resolution

Racemic Mixture:

Whenever we synthesize an enantiomer in the laboratory, the other enantiomer of the same compound is also formed simultaneously because the two forms differ only in the tetrahedral arrangement of the atoms or group of atom about asymmetric carbon. Thus, we obtain a mixture which when dissolved in water does not rotate the path of plane-polarized light as the rotation due to one form cancels out the rotation due to the other form. Such a mixture is referred to as a racemic mixture.

Thus, an equimolar (1:1) mixture of the enantiomers (dextro and laevo forms) is called a racemic mixture. It is represented as dl forms and will be optically inactive.

The process of converting d or l form of an optically active compound in a racemic form (dl) is called as racemisation and the process of separation of a racemic mixture into d- or l- forms is called resolution.

Resolution of Racemic Mixture:

It is quite difficult to separate enantiomers because they possess similar physical properties and cannot be separated by ordinary methods such as fractional distillation or fractional crystallisation. Resolution of the racemic mixture is carried out by special techniques.

(i) Mechanical Separation- This method was given by Pasteur in 1848. The method is applicable to only solid substances which form well-defined crystals and the crystals’ shapes of the two optical isomers are enantiomorphous. The two types of crystals present in a racemic mixture can be sorted out with the help of a magnifying lens and small forceps.

(ii) Biochemical Method- This method was given by Pasteur in 1858. In this method, one component (d or l) of a racemic mixture is destroyed by a biochemical process. Certain microorganisms such as yeast, moulds and bacteria possess a unique property of selectively assimilating only one component of a racemic mixture and leaving the other untouched in the solution. The component left in the solution can be separated by fractional crystallization.

(iii) Chemical Method- This method was also given by Pasteur in 1858. This is the most general and perhaps the best method for resolution.

In this method, the enantiomers of a racemic mixture are converted into diastereoisomers with the help of a pure enantiomer of some other optically active compound. These diastereoisomers can easily be separated because they possess different physical properties. The diastereomers thus obtained back into original components with the help of a suitable reagent.

Following examples illustrate how the compounds containing different functional groups can be resolved-

  • Acids- Racemic modifications of acids can be resolved with the help of optically active bases such as brucine, strychnine, quinine, morphine etc.
  • Bases- Racemic modifications of the base can be resolved with the help of optically active acids such as tartaric acid, malic acid, camphor-β-sulphonic acid, α-bromocamphor-π-sulphonic acid etc.
  • Alcohols- A racemic mixture alcohols is resolved by the reaction of an optically active base with the phthalate or succinate esters of the alcohols present in the mixture. It gives diastereoisomeric salts, which are separated by fractional crystallization and on treatment with HCl followed by hydrolysis with NaOH yield enantiomeric components of the racemic mixture.
  • Aminoacids- Aminoacids are resolved by first deactivating the amino group via acetylation and then treating them with optically active base.
  • Aldehydes and Ketones- These can be resolved with the help of optically active reagents such as methyl hydrazine, menthyl semicarbazide etc.

(iv) Kinetic Method- This method is based on the fact that enantiomers react with an optically active substance at different rates. Due to a difference in kinetics of the enantiomers they can be separated. For example- a racemic mixture of mandelic acid can be separated with l-menthol. The rate of reaction of d-mandelic acid with l-menthol is more than that of l-mandelic acid.

(v) By chromatography- Resolution of racemic mixtures can also be carried out by the chromatographic technique. Certain optically active adsorbents possess the property of selective adsorption of either d- or l- form of a racemic mixture.

Comments (No)

Leave a Reply