The topic of this lecture will be the resolution of enantiomers. This is a fancy way of saying the separation of enantiomers, like the purifications we've done in lab. Enantiomers, unlike diastereomers, have very similar physical properties, except for their ability to rotate plane polarized light in opposite directions. Their similarity in physical properties makes them much more difficult to separate than diastereomers.
They have the same melting points, the same boiling points, the same densities, the same solubilities, and that makes it so that the typical ways that we purify molecules, such as extraction or chromatography or distillation, won't work with enantiomers. So how do we separate enantiomers? We can use something called chiral chromatography, where our stationary phase contains a chiral molecule.
And so different enantiomers, which have opposite chiralities, interact with the stationary phase differently. Another way that we can obtain a single enantiomer is from a biological source. Biological systems are chiral and oftentimes only produce a single enantiomer rather than a racemic mixture like a lot of organic syntheses do.
The final way to obtain a single enantiomer is through a method called chemical resolution. In chemical resolution, we take a racemic mixture and react it with a pure chiral compound. This reaction produces two diastereomers. Since diastereomers have different physical properties, we can then separate the two compounds based on their physical properties. Let's look at an example.
Say we would like to separate a mixture of R and S-butanol. 2-butanol looks like this. Take a moment and pause the video. and draw the R and S enantiomers of this molecule.
The two enantiomers of butanol look like this. The one on the left is R, and the one on the right is S. If we have a mixture of the R and S enantiomers, a racemic mixture, which is one-to-one, we can react this mixture with another chiral molecule that is able to be obtained as a single stereoisomer.
This is called a resolving agent. Oftentimes, resolving agents are obtained from biological sources. The one that we're going to use in this example is called tartaric acid. The RR tartaric acid can be obtained from wine.
Tartaric acid is a carboxylic acid, and we can react an alcohol and a carboxylic acid to produce an ester. This is the reverse of the sponification reaction. we did in lab.
The carboxylic acid plus the alcohol in the presence of acid catalyst gives us the ester and water. The water molecules produced from the hydroxyl group of the carboxylic acid and the proton from the alcohol. Using this reaction, we can react tartaric acid with our racemic mixture of R and S-tubutinol to produce two diastereomeric products.
This process is much easier to follow if we draw all of the molecules as Fischer projections. Tubutinol has a single chiral center that can be either R or S. Take a moment and assign the absolute stereochemistry to the material. to each of the structures that I've drawn. The top structure is the S enantiomer, and the bottom structure is the R enantiomer.
We can react the one-to-one mixture of the S and R enantiomers with RR tartaric acid in the presence of an acid catalyst to give us the ester. The reaction of the S enantiomer of 2-butanol with RR tartaric acid gives us a product. that has three stereocenters that have S, R, and R stereochemistry.
The stereochemistry of the centers has not changed. When we react the R enantiomer of 2-butanol with RR tartaric acid, we get another ester with different stereochemistry. Again, the absolute stereochemistries of these centers have not changed throughout the reaction. But the two enantiomers of 2-butanol give us two diastereomeric products.
And because diastereo... have different physical properties, we can now separate these two compounds quite easily.