1. Stereochemistry 1. Stereoisomerism 2. Chirality
Chapter 3
Stereochemistry
1. Stereoisomerism
2. Chirality
3. Naming stereocenters - R/S configuration
- working with R/S [Home Page -Practice ]
4. Acyclic Molecules with 2 or more stereocenters
5. Cyclic Molecules with 2 or more stereocenters
6. Properties of Stereocenters
7. Optical activity
8. Separation of Enantiomers, Resolution
9. Significance of Chirality in the biological world
Lect 6, Sept 17, 2002
Lecture 6, Feb 11, 2003 21

2. Looking for a change in the polarized plane
achiral
sample
no change in the plane

3. Looking for a change in the polarized plane
CHIRAL
rotates the plane

4. R-(+)-2-methyl-1-butanol S-(-)-2-methyl-1-butanol
 20 D D 20

50/50 mixture of S and R
50% S(-5.75o) with 50% R(+5.75o)
net rotation = 0
RACEMIC MIXTURE

5. Specific Rotation 
Observed  dependent on (conc.), (cell length), (temp.)
Specific Rotation
[]t =
(degrees)
l (dm) c (g/mL) 
t = temperature
 = wavelength
l = path length (dm)
c = concentration (g/mL)

6. Example: A sample of 2 g in 10 mL of solution
Specific Rotation
[]t = 
l c 
Example: A sample of 2 g in 10 mL of solution
measured in a 25 cm long cell
gives an observed  of +134o
The specific rotation is?
(+134o)
2.5 (0.2)
[]t = 
[]t = 
+268o
(actually deg/cc2g-1)

7. Optical purity Absolutely pure (100%) cholesterol has a specific rotation of -39o.
synthetic sample may contain:
the enantiomer -  (or < -39o)
or a diastereomer -  (or < -39o)
or other junk -  (or < -39o)

8. Optical purity Absolutely pure cholesterol has a specific rotation of -39o.
()
1dm (1g pure)
observe
 = -39o
()
1dm (?g+crap )
[-]t = 
 = less than -39o 
1dm ( )
[-]t =
-38.6o
 = -38.6o
0.99g+0.01g
(-35.1)
1dm ( )
[-]t = 
 = -35.1o
0.9g+0.1g
(-31.2)
1dm ( )
[-]t = 
 = -31.2o
0.8g+0.2g

9. Mix is between100% S and 50/50 (S/R)
Pure (S)-(+)-2-bromobutane
specific rotation o
But what if observe optical rotation = +9.2?
Not pure, possibly a mix of R and S!!!!
+23.1o > +9.2o < 0o
Mix is between100% S and 50/50 (S/R)
optical purity

10. Pure (S)-(+)-2-bromobutane specific rotation - +23.1o
But what if observe optical rotation = +9.2?
Not pure, possibly a mix of R and S!!!!
observed (100%)
 of pure enantiomer =
+9.2(100%)
+23.1
optical purity =
= 40%
40% optical purity i.e. 40% excess of S isomer
40% excess = 40%S + (60%S/R mixture)
+ (30%S+30%R)
The sample has 70%S and 30%R

11. enantiomeric excess or ee (= optical purity)
(moles 1 isomer) - (moles of other)
(moles of both enantiomers)
X 100%
(.70) - (.30)
(1.00)
ee =
X 100%
ee = 40%

12. Solution of 10 mL of 0.1 M R enantiomer
30 mL of 0.1 M S enantiomer
observed rotation = +4.8
What is the specific rotation of each enantiomer?

13. Solution of 10 mL of 0.1 M R enantiomer
30 mL of 0.1 M S enantiomer
observed rotation = +4.8
What is the specific rotation of each enantiomer?
opt. purity =
mole S - mole R
(moles of S + R)
3 - 1
3 + 1 2 4
opt. purity = =
50% =
50%
+4.8 X
X = (S) observed +,  S

14. What is the optical rotation of a sample of
(+)-2-bromobutane ([]25 = +23.1) that is 75% optically pure?
What percentage of (+) and (-) enantiomers are present in this sample?

15. opt pure rotation mix (+)%/(-)% 75% +17.3 87.5/12.5
What is the optical rotation of a sample of (+)-2-bromobutane that is 75% optically pure? What percentage of (+) and (-) enantiomers are present in this sample?
([]25 = +23.1) 
[] 
23.1
75% =
opt. purity = ee =
25o D

(+)75% + racemic(+/-)
or (+)75% + (12.5%(+) +12.5%(-))
or (+)87.5% / (-)12.5%
opt pure rotation mix (+)%/(-)%
75% /12.5

16. These similar “S” compounds rotate light in the opposite direction.
(S)-(+)-2-bromobutane, = +5.75
(+) or (-) a measured physical property - not predictable
These similar “S” compounds rotate light in the opposite direction.
NaOH
(S)-(+)-lactic acid
sodium (S)-(-)-lactate

17. Resolution (separation):
Convert mixture of enantiomers - same properties
TO diastereomers - different physical properties, can be separated.

18. Resolution R S S R R R S S 2 equivalents R1 + R1 pure R1 R1 pure
new compounds
diastereiomeric mixture S +
enantiomeric mixture
different
compound
2 equivalents R1 S R
non-separable
separate
remove R1 R R1 S R
pure
pure S

19. Resolution by acid-base reactions
remove amine
Pure-Sb
----resolved----
racemic
mix

20. Resolution Examples of enantiomerically pure bases R CH =CH H CH =CH H2
=CH H CH 2
=CH H H H H R HO H N N H HO H
CH3O N N
(+)-cinchonine [R=H]
(+)-quinidine [R = OCH3]
(-)-quinine

21. []D = -127o HCCl3 from Strycnos seeds (S nux-vomica)
brucine
Strychnine no methoxy groups

22. Resolution [] = 0 enantiomeric mixture pure enantiomer + R S S R S S

23. Resolution [] = 0 enantiomeric mixture []25 = -8.2 pure enantiomerD
[] = 0
pure
enantiomer R S
Resolution S
[]25 = +8.2 D

24. lipase
>69%ee
50/50 mix
R-Enzyme

25. lipase >69%ee R-Enzyme A 50/50 enantiomeric mixture of esters
forms R-acid and recover S-ester.
R-Enzyme

26. CHEMICAL & ENGINEERING NEWS Oct 23, 2000 pg 55
Chiral Drugs Sales top $100 Billion
C&E NEWS Oct 1, 2001 pg 79
40% of all dosage-form drug sales in 2000 were single enantiomers.
(Now >>50% single enantiomer)

27. Some drugs are racemic mixtures, e.g.
antidepressants:
Wellbutrin (bupropion, in Zyban)
Effexor (venlafaxine hydrochloride)

28. Ibuprofen Naproxen - S isomer
S isomer particularly active, but R slowly converted to S
Naproxen - S isomer
(R enantiomer liver toxin)

29. R-ketamine hallucinogenic S-ketamine anaesthetic
R|S

30. analgesic DarvoN | NovraD antitussive
2S,3R-propoxyphen | 2R,3S-propoxyphen
R / S
R \ S

31. Thalidomide R- sedative, anti-inflammatory, Crohn’s disease S -teratogenic
(but thalidomide racemized in the body)