There are some stereochemical reactions that result in the presence of enantiomers. When moving forward with a practical organic synthesis, how does one usually separate them in order to continue with one of the enantiomers?
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6$\begingroup$ If you're a bad-ass like Louis Pasteur, you do it with a microscope and a pair of tweezers. $\endgroup$– R.M.Dec 8, 2016 at 23:49
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3 Answers
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There are several ways that enantiomers can be separated, but none of them are particularly simple.
The first way to separate them is chiral chromatography. In chiral chromatography, silica gel is bonded to chiral molecules to form what is called a chiral stationary phase. The enantiomers will then separate as they run down the column because one of the enantiomers will interact more strongly with the column and "stick" in place. Chiral sugars (ex. cellulose) are frequently used in chiral chromatography.
The second common method is to react the enantiomers with another chemical to form diastereomers. While enantiomers are identical in terms of chemical properties, diastereomers are not. Diastereomers can be created by reacting a mixture of both the enantiomers with another chiral molecule, such as s-brucine, which is commonly used because it is cheap. Diastereomers have different chemical properties (for example melting points), so it is much easier to separate them. Then, after separation, the enantiomers can be recovered from the single diastereomer.
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$\begingroup$ Brucine seems like a scary chemical to work with in large quantities. Obviously not used for the same substrates, but tartaric acid sure seems less scary. $\endgroup$ Mar 9, 2016 at 4:56
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The physicochemical properties of enantiomers being the same (except for optical activity), one needs to make use of the chirality of the molecules to separate them. This is done by asymmetrizing the environment of the molecules. I'll explain.
Lets say you have a racemic mixture of a chiral carboxylic acid. To effectively differentiate both enantiomers, you can use an enantiopure amine to form a salt with your carboxylic acid. You've then created two diastereomers from the combination of chiral molecules. Since the physical properties of diastereomers are different, you can then separate them.
One way to do this would be to crystallize your salts, extract/wash them, then pass them through a flash chromatography column, and then get rid of the amine.
Another option would be to use a chiral chromatography column, which would effectively have the same effect.
There are also analytical techniques that can differentiate between enantiomers, for example MEKC used with chiral cyclodextrins.
I think you've gotten the point that, to separate enantiomers, you need to create diastereomers.
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This isn't best solution to this problem, as its usage would be quite limited, but nonetheless it is still a solution: using enzymes specific to the enantiomer you wish to remove. As an example, using enzymes specific for D-amino-acids would leave you with its L-counterpart untouched. They can then be separated as the "product" form of the D-amino-acid is likely to have changed its physical properties.
