Chapter 1. Stereoisomerism

• symmetry elements Little Eliel “Symmetry” symmetry planes, symmetry axes, inversion centers p. 45-58 … • point groups chiral point groups • enantiomers and diastereomers in chiral point groups: chiral centers chiral axes planes of chirality • notation: Fischer D,L Cahn, Ingold, Prelog R,S • resolution of a racemic mixture and its detection

For symmetry, also check out http://www.reciprocalnet.org/edumodules/symmetry, a very nice site. 4. Racemates (racemic mixtures)

- 1:1 mixture of enantiomers

I. Detection Optical activity - a chiral compound is optically active - it rotates the plane of linearly polarized light in a polarimeter

andromeda.rutgers.edu/~huskey/335_lec.html - linearly polarized light is a linear combination of two waves:

left +right circularly polarized light: - experience a different refraction index in the chiral sample (“diastereomeric interactions”) - slow down in the sample to a different extent ? -“circular birefringence” Polarized light

linearly polarized wave

two linearly polarized waves: a) in phase b) out of phase Polarized light continued

This is what happens to linearly polarized light in the polarimeter:

Here the right circularly polarized wave slows down in the sample.

back 4. Racemates continued

- rotation of the plane of linearly polarized light in a polarimeter: clockwise: +α for either R or S: (R)-(+)-… or (S)-(+)-… anticlockwise: -α for either R or S: (R)-(-)-… or (S)-(-)-… - racemic mixture is given as (±) - optical activity establishes the non-racemic character of a sample - magnitude of the rotation α is normalized as “specific rotation” [α]

T 2 -1 Biot’s law: = []ααλ cl [α] in deg cm g λ is usually 589 nm (Na D-line) T in °C solvent needs to be listed

[α] = f(T) f(c) www.youngscientists.co.uk/node/95

O 21 21 []α D = +167 [α]D = +182 (c = 46 g/100mL in benzene) ? H []α 25 [α]21 Ph D = +162 D = +215 (c = 1.5 g/100mL in benzene)

- racemic mixture or meso-compound: no optical activity! 4. Racemates continued

- quantitative treatments of the optical activity (non-racemic character): A. Optical purity, P

[]α observed P = P = +1 or -1 pure enantiomer []α max for the pure enantiomer P = 0 racemic mixture

- possible problems: change in T, c, solvent crypto-chirality accidental degeneracy

B. Enantiomeric excess, %ee [][]− SR %ee = 100 , where [R] > [S] [][]+ SR

: excess over ⇒ - non-racemic 80:20 mixture of enantiomers 60% ee racemic mixture - the “diastereomeric excess”, %de, is defined similarly Insert 4. Racemates continued

I. Detection - other methods can be used to detect racemic mixtures (IR, NMR…) - sometimes a modification step is needed: diastereomeric mixtures (will look at this in more detail later)

1H NMR

O + Ph Ph NH2 Cl R - HCl R,S CH3O H

O O Ph + Ph Ph R NH R Ph S NH R

CH3O H CH3O H singlet singlet singlet singlet

Jacobus, Raban, J. Chem. Ed. 46, 351 (1969) II. Resolution (closely linked to detection!)