Introduction to Organic Chemistry: Question 4

Worked solution

Part (a): Is C3 of compound Q a chiral centre?

A carbon atom is a chiral centre (or stereocentre) if it is bonded to four different atoms or groups.

For compound Q, $\text{CH}_3\text{CH(CH}_3\text{)CH(OH)CH}_2\text{CH}_3$, number the chain C1 to C5 and look at what is attached to each carbon of interest:

• C2 is bonded to C1 ($\text{-CH}_3$), the branch methyl ($\text{-CH}_3$), C3, and H. Two of these four groups are identical ($\text{-CH}_3$ and $\text{-CH}_3$), so C2 is not a chiral centre.
• C3 is bonded to:
  • a hydroxyl group, $\text{-OH}$
  • a hydrogen atom, $\text{-H}$
  • the C2 side of the chain, which (including its own methyl branch) is an isopropyl group, $\text{-CH(CH}_3\text{)}_2$
  • the C4–C5 side of the chain, an ethyl group, $\text{-CH}_2\text{CH}_3$

These four groups ($\text{-OH}$, $\text{-H}$, isopropyl, ethyl) are all different from one another, so C3 is a chiral centre.

Part (b): Distinguishing the enantiomers experimentally

The two enantiomers of Q are identical in almost every ordinary physical and chemical property (melting point, boiling point, solubility, density, refractive index, and so on), because these depend only on the strength of intermolecular forces between molecules, and the enantiomers have exactly the same atoms held together by exactly the same bonds. The one property that does differ is their effect on plane-polarised light.

Using a polarimeter, monochromatic light is first plane-polarised and then passed through a solution of the compound. Each pure enantiomer rotates the plane of polarisation by the same angle, but in opposite directions, one rotates it clockwise (dextrorotatory, ”+”) and the other rotates it anticlockwise (laevorotatory, "$-$") by an equal amount. This is how the two pure samples can be told apart.

If a racemic mixture (an equal, 1:1 mixture of both enantiomers) were tested instead, the clockwise rotation caused by molecules of one enantiomer would be exactly cancelled by the equal anticlockwise rotation caused by molecules of the other. The mixture would therefore show no net rotation of the plane of polarised light. It is described as “optically inactive” even though it is made up entirely of chiral molecules.

Part (c): Identical physical properties, different biological behaviour

The two enantiomers of Q contain exactly the same atoms joined by exactly the same bonds, with the same bond lengths and bond strengths, they differ only in the three-dimensional arrangement of the four groups around the chiral centre (they are non-superimposable mirror images). Because ordinary physical properties like melting point and boiling point depend on the strength of the intermolecular forces between molecules (or between a molecule and an achiral solvent), and this depends only on the identity of the atoms and bonds present rather than on their 3-D arrangement relative to a chiral reference, the two enantiomers have identical melting points and boiling points.

However, biological systems are built from chiral molecules themselves. Enzymes and receptor proteins, for example, are constructed almost entirely from a single set of chiral amino acids. A chiral receptor site can typically only bind effectively to one specific 3-D arrangement of a molecule, in the same way that a right hand fits comfortably into a right-hand glove but not into a left-hand one. As a result, the two enantiomers of a chiral drug molecule can produce very different biological effects: one enantiomer might be therapeutically active while the other is inactive, or in some cases the two enantiomers can even have entirely different (including harmful) effects. This is why, when a chiral compound is developed as a drug, chemists often need to synthesise or separate a single enantiomer rather than supply the racemic mixture, to ensure the correct, and only the correct, biological effect is obtained.

Final answers

• (a) A chiral centre is a carbon bonded to four different groups; C2 is not chiral (it has two identical $\text{-CH}_3$ groups), but C3 is chiral because its $\text{-OH}$, $\text{-H}$, isopropyl and ethyl groups are all different
• (b) Polarimetry: pure enantiomers rotate plane-polarised light by equal angles in opposite directions; a racemic mixture shows no net rotation
• (c) Enantiomers have identical bonds/intermolecular forces (so identical mp/bp), but chiral biological receptors bind them differently, so single-enantiomer synthesis matters for drugs