Stereochemistry, Chirality, and Optical Activity

Problem # 744

After a sample of optically pure (S)-2-ethyl-cyclohexanone is dissolved in an aqueous solution for several hours, a significant loss of optical activity is observed. Explain.

Solution

Carbonyls are in equilibrium with their enol forms. This process is called keto-enol tautomerization. (See problems 738 and 739). So when this compound is placed in water a small amount of it will constantly be converted to its enol form, and then back again to the carbonyl form.

But the enol form is achiral! (the alpha carbon is sp² instead of sp³as in the carbonyl form).

So when the achiral enol goes back to its carbonyl form, half will become (S) and the other half will become (R). The stereocenter becomes "scrambled." The process of an optically pure compound becoming a racemic mixture is called racemization.

Problem Details

MendelSet practice problem # 744 submitted by Matt on July 27, 2011.

Subject: Organic Chemistry

Subject Topic(s): Stereochemistry, Chirality, and Optical Activity, Carbonyl Alpha-Substitution Reactions (Enols and Enolates, Malonic Ester Syn, Stork)

Question Type: Concept (explain why this is so..)

Keyword(s): keto-enol tautomerization, racemization

Problem # 532

Let's work through a chiral resolution. Write out the structure of the indicated compound in each box. Include stereochemistry.

Why is it possible to separate the (R,R) and (R,S) salts?

Solution

The starting material (2-aminobutane) is a racemic; it has equal amounts of R and S enantiomers.

Enantiomers have the same the same chemical and physical properties, so we can't separate them using common lab techniques, such as recrystallization, chromatography, etc. But diastereomers can have different properties, and we can exploit this fact to separate otherwise inseparable compounds.

Adding an optically pure acid to the amine produces a diastereomeric mixture of salts which can be separated. Adding a base (NaOH) "breaks" the salt and allows us to isolate the pure R or S amine.

We are able to separate the (R,R) and (R,S) salts because they are diastereomers and so have different chemical and physical properties.