Analysis and Separation of Stereoisomers

Question 1

Racemization

Answer 1

Process of converting one enantiomer to a racemic mixture of two possible enantiomers

Question 2

Methods of racemization

Answer 2

Thermal: Heating (biaryls, cyclophanes)
Base induced: Enolization of acidic H atom
Acid induced: Enolization of aldehyde/ketone

Question 3

Epimerization

Answer 3

Epimers = diastereomers which differ in their configuration around only one stereocentre

Any process converting a compound into its epimer

Question 4

What does epimerization produce?

Answer 4

Diastereomers with different physical properties, meaning they have different heats of formation (different energies/stabilities)

Question 5

Resolution

Answer 5

Process where a mixture of enantiomers is separated into its constituent stereoisomers

Question 6

Racemic compound

Answer 6

1:1 mixture of enantiomers
Optical rotation = 0

Question 7

Conglomerate

Answer 7

Only one enantiomer present
Optical rotation not equal to 0

Question 8

Entrainment

Answer 8

Induced crystallization of one enantiomer over another (relies on conglomerate)

Question 9

What do chiral salt formation and selective recrystallization allow?

Answer 9

Turn a racemic mixture into a mixture of diastereomers, can exploit their physical differences for separation

Question 10

Kinetic resolution

Answer 10

When racemic mixtures interact with another chiral species, the transition states are diastereomeric (have different energies)

Question 11

Methods for determining enantiomeric excess

Answer 11

Chromatography with chiral stationary phase (one will elute earlier, one later)
(area under peak = relative amounts)

NMR with a chiral shift agent
Polarimetry (known and varying ee’s, need linear plot)

Question 12

Determination of absolute configuration

Answer 12

Chiroptical methods (ORD, CD, CPE)
X-ray crystal structure

Question 13

Symmetry elements

Answer 13

Axis of symmetry (rotation around axis by 360° / n)
Plane of symmetry (mirror plane)
Inversion centre (point in molecule that all atoms can invert through)
Rotation-reflection axis (rotation around an axis by 360° / n followed by a reflection in a plane perpendicular to the axis*)

• order does not matter

Question 14

Point groups

Answer 14

Symmetry-related categories a specific conformation of a molecule can be classified into

Some point groups (like absence of Sn) are inherently chiral, but chirality can be disrupted if there are multiple conformations