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Racemic Modification and Resolution of Racemic Mixture

Racemic modifications or racemates are enantiomer mixtures of (+) and (-).

Racemic Modification

Racemic modifications or racemates are enantiomer mixtures of (+) and (-). When the enantiomers of a substance are mixed in equal amounts, a molecule of the isomer is canceled exactly by a molecule of the enantiomer. Therefore, the racemate has no overall optical rotation. There is no optical action in a racemic modification. The prefix (±) indicates that the sample is racemic. For example, (±)-2-methyl-1-butanol.

In the absence of a chiral catalyst, the reaction product will always be a racemate if one of the starting materials is chiral.

Nevertheless, pure enantiomers can be synthesized using chiral catalysts or agents.

Methods of Racemic Modifications

Mixing - A racemic modification can be achieved when two equal amounts of Dextro (+) and Levo (-) isomers are closely mixed together.

Chemical synthesis - Without chiral catalyst, a chiral starting material will always produce a chiral racemate as a product of the reaction. A reaction between hydrogen cyanide and acetaldehyde (chiral) leads to CH3CHOHCN, which contains both forms of acetonitrile in equal amounts.

Thermal racemization - Heat can cause racemization in optically active materials. This leads to a temporary break in one of the four stereocenter bonds. A separating atom or group joins back to the stereocenter to yield another enantiomer, e.g., when the optically active enantiomer of α-phenethyl chloride is distilled, it is converted into its racemic enantiomer.

Walden inversion - This process is called Walden inversion, in which 2-isooctane is racemized by potassium iodide in refluxing acetone.

Epimerization - Specifically, it describes the change in carbon atom configuration at a stereocenter in a compound having multiple stereocenters. Diastereomers are therefore converted to one another.

Mutarotation - Biologically, it is a change that occurs when a solution of optically active substance rotates over time until it achieves equilibrium. The process of mutarotation results from epimerization or spontaneous structural changes. Temperature, solvent, and catalyst all play a role in mutarotation. The mutarotation of glucose is catalyzed by acid-base.

Resolution of Racemic Mixture

Known as resolution, this is the process of splitting a racemate into its enantiomers. Because enantiomers share the same physical properties (bp, mp, solubility), conventional methods cannot separate them. If enantiomers are converted into diastereomers, their differences in physical properties can be used to separate diastereomers. Pure enantiomers can be regenerated by separating them from their respective diastereomers.

For example,
A chiral base with D-configuration can be used to convert a racemic mixture of enantiomers into salt. You will discover two diastereomers in the salt: (D acid, D base) and (L acid, D base). Because of their differences in physical properties, the diastereomeric salts are completely separated. Separated diastereomeric salts can be dissociated to regenerate D-acid and L-acid, respectively.

A chiral base such as brucine, strychnine, l-phenyl ethanamine can be used to dissolve racemic acids. Racemic bases can also be treated by using chiral acids such as (+) tartaric acid, (–) malic acid, (–) mandelic acid, and (+) camphoric acid. Diastereomeric esters can be created by converting racemic alcohol with a chiral acid. If they are liquid, it becomes difficult to separate these diastereomeric esters.

As an alternative to a full ester in such cases, a half ester is synthesized with one free carboxylic group. The chiral nature of brucine's salts allows it to be separated from their diastereomeric forms after crystallization. During the hydrolysis of respective diastereomeric salts, 2-butanol is regenerated into its pure enantiomer.



Biological mechanisms for resolution: In some mold, bacteria, and fungi, one enantiomer is eliminated faster than the other. Molds like Penicillium glaucum selectively destroy dextro isomers when grown with racemic mixtures; they leave only pure Levo isomers.

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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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