Resolution of Racemic Mixture Preparation and Properties

Resolution of Racemic Mixture Preparation and Properties

→ The process of separation of racemic mixture into the enantiomers is called resolution. Most of naturally occurring compounds are optically active because the enzymes that bring about their formation and often the raw materials from which they are made are themselves optically active. But most of the synthetic organic reactions result in the formation of the racemic mixture.

→ Since, the enantiomers present in the racemic mixture have identical physical properties (like melting points, boiling points, zefractive indices, reactivities, and solubilities etc.), except for direction of rotation of polarized light, hence they cannot to be separated by the usual simple methods like fractional crystallization or fractional distillation, etc.

→ There are many methods for their separation, but the most widely used is by the chemical method in which racemic mixture is converted to diastereomeric mixture.

Resolution of Racemic Mixture Preparation and Properties

→ Mechanical Separation Method : This was the first method of separation of racemix mixture used by Louis Pasteur, and it is mainly of historical interest. This involved mechanical separation of the crystals of one enantiomer from the other in a racemic mixture based on differences in their shapes.

→ Louis Pasteur did so by growing the crystals of tartaric acid and they looked like mirror images. He then used a microscope and tweezers to separate the crystals from each other. But this method has limitations as it is very time consuming andonly used on crystalline solids.

→ Bio-chemical Separation Method : In this method, certain bacteria, yeast or mould are allowed to grow in a dilute solution of the racemic mixture. It reacts with or consumes only one of the enantiomers for its growth and give other small products while the other is left behind pure.

→ For example, when allowed to grow in racemic mixture of ammonium tartarate, it consumes (+) ammonium tartarate while pure (-) ammonium tartarate is obtained as the product. This method also has some limitations as only one isomer can be obtained.

Resolution of Racemic Mixture Preparation and Properties

→ Also the yield of that isomer is also very poor because only dilute solution can be used. Similarly, acetylation of dl-amino acids takes place in which amino group can be protected. Now, yeast is added to this racemic mixture, here, enzyme amylase destroys l-acetyl derivative selectively by hydrolysis. d-derivative is unaffected. By hydrolysis of d-acetyl derivatives d-amino acids can be obtained.

Resolution of Racemic Mixture Preparation and Properties 1
Resolution of Racemic Mixture Preparation and Properties 2

Some of the limitations of this method are:

  • Selection of suitable bacteria is very difficult.
  • Bacteria reproduces in dilute solutions. Hence, to obtain bacteria by dilute solutions is time taking.
  • Sometimes one isomer is destroyed by bacteria. Thus, it is very costly method.

→ Column Chromatographic Method : A racemic mixture can also be resolved with the help of column chromotography. The solution of the racemic mixture is prepared in a suitable solvent and is passed through a column packed with a suitable chiral adsorbent. One of the enantiomers is selectively adsorbed on the surface of adsorbent.

→ It is then diluted with a suitable solvent and the solution is collected at the bottom of the column, which contains pure enantiomer. For example, first of all. Henderson and Rule in 1939, resolve d and l isomers by adsorbing D-lactose for resolution of camphor derivative. (p.phenylene bis (imino) camphor).

Resolution of Racemic Mixture Preparation and Properties

→ Chemical Methods : Consider a racemic mixture of enantiomeric organic acids, (±)-HA. It can be separated into pure enantiomeric acids by reaction with an optically active base, say a laevo rotatory base, (-)-B.

→ The mixture of enantiomeric acids on reaction with an optically active base results in the formation of two diastereomeric salts as shown in figure. These diastereoisomeric salts have, of course, different physical properties, including solubility in a given solvent. They can, therefore, be separated by a simple technique, i.e., fractional crystallization.

Resolution of Racemic Mixture Preparation and Properties 3

→ The optically active acid can then be recovered from each salt by the addition of a strong mineral acid. The most commonly used optically active organic bases for this purpose are (-)-Brucine, (-)-Quinine, (-)-Strychnine. and (+)-Cinochonine. For example, resolution of a racemic mixture of 2-chioro propanoic acid by salt formation with (+) 1 -Phenylethyla mine.

Chemistry Notes