‫האוניברסיטה העברית‬

‫כימיה אורגנית לתלמידי רפואה‪ ,‬מדעי‬

‫הרפואה‪ ,‬ורפואת שיניים‬
‫‪69120‬‬

‫דר' נורמן מטאנס‬

‫המכון לכימיה‬
‫בניין פלדלפיה‪ ,‬חדר ‪320‬‬
‫‪02-6586562‬‬
‫‪metanis@mail.huji.ac.il‬‬ ‫‪1‬‬
 Conformations of Alkanes:
Rotation about Carbon–Carbon Bonds

2
 Different Conformations of Ethane

• A staggered conformer is more stable than an eclipsed

conformer
• Torsional strain: repulsion between pairs of bonding
3
electrons
 Conformations of Butane
• Steric strain: repulsion between the electron clouds of
atoms or groups

4
 Cycloalkanes: Ring Strain
• Angle strain results when bond angles deviate from the
ideal 109.5° bond angle

5
• The chair conformation of cyclohexane is free of strain

6
The Conformations of Cyclohexane
and Their Energies

7
The Conformations of Cyclohexane
and Their Energies

8
Ring Flip in Cyclohexane
Monosubstituted Cyclohexane
Steric hindrance

“no“ steric hindrance

4.8 % 95.2 %

10
disubstituted Cyclohexane

12
disubstituted Cyclohexane

same stability;
50% one equatorial & one axial 50%

less table more stable 13

0.22% 99.78%
14
 Isomers
Nonidentical compounds having the same molecular
formula

15
Do not interconvert under ambient conditions
Cis-Trans Isomers

16
Caused by restricted rotation
Structure of Alkene

17
Isomers of Alkene

18
Conversion of alkene isomers requires breaking of
the p bond between the two sp2 carbons

19
Dipole Moments of Alkene Isomers

Cis- and trans- compounds have different physical

properties, and may be separated

20
Cis-Trans Interconversion in Vision

21
E and Z isomers

22
Naming by the E,Z System
Rule 1: Consider the atomic number of the
atoms bonded directly to a specific sp2
carbon.

23
Rule 2: If there is a tie, consider the atoms
attached to the tie.

24
Rule 3: Multiple bonds are treated as attachment
of multiple single bonds.

25
Rule 4: Rank the priorities by mass number in
isotopes.

26
Isomers with a chiral center

27
Achiral compounds have superimposable mirror images

Chiral compounds have nonsuperimposable mirror

images; they do not have a plane of symmetry

Non-superimposable Superimposable

28
Non-superimposable Superimposable

29
Enantiomers

30
 Enantiomers
nonsuperimposable mirror-image molecules

31
Drawing Enantiomers

Perspective formula

Fischer projection 32
 Naming Enantiomers
The R,S system of nomenclature
Rank the groups (atoms) bonded to the chirality center

33
Orient the lowest priority (4) away from you

Clockwise = R configuration
34
Counterclockwise = S configuration
Orient the lowest priority (4) away from you

Counterclockwise = S configuration Clockwise = R configuration

35
Naming from the Perspective Formula
1. Rank the groups bonded to the asymmetric carbon
1

2
3

2. If the group (or atom) with the lowest priority is

bonded by hatched wedge,

36
3. If necessary, rotate the molecule so that the lowest
priority group (or atom) is bonded by a hatched wedge

4. You can draw group 1 to group 2, passing group 4,

but never 3

37
 Naming from the Fischer Projection
1. Rank the groups (or atom) that are bonded to the asymmetric
carbon and draw an arrow with the highest priority to the lowest
priority
Cl

CH3CH2 CH2CH2CH3
(R)-3-chlorohexane
H
2. If the lowest priority is on a horizontal bond, the naming is
opposite to the direction of the arrow
CH3

H OH (S)-2-butanol
CH2CH3
38
3. The arrow can go from group 1 to 2, passing group 4, but not
group 3
CO2H

H CH3
(S)-lactic acid
OH

A Fischer projection can only be rotated 180 ° in the plane

of the paper to yield the same molecule

39
Enantiomers share many physical properties.
Chiral compounds are optically active; they rotate the
plane of polarized light.

Clockwise (+) Counterclockwise (-)

Different from R,S configuration

Achiral compounds do not rotate the plane of polarized

light. They are optically inactive. 40
Chiral compounds are optically active; they rotate the
plane of polarized light.

Clockwise (+) Counterclockwise (-)

Different from R,S configuration

Achiral compounds do not rotate the plane of polarized

light. They are optically inactive. 41
Chiral compounds are optically active; they rotate the
plane of polarized light.

Clockwise (+) Counterclockwise (-)

Different from R,S configuration

Achiral compounds do not rotate the plane of polarized

light. They are optically inactive. 42
Chiral compounds are optically active; they rotate the
plane of polarized light.

Clockwise (+,d) Counterclockwise (-,l)

Different from R,S configuration

Achiral compounds do not rotate the plane of polarized

light. They are optically inactive. 43
A polarizer measures the degree of optical rotation of a
Compound, polarimeter
The observed rotation (a)


  =Τ
λ
lxc
T is the temp in °C
 is the wavelength
 is the measured rotation in degrees
l is the path length in decimeters
c is the concentration in grams per mL
Each optically active compound has a characteristic specific 44
rotation
A racemic mixture (), which contains an equal amount
of the two enantiomers, is optically inactive

optical purity = observed specific rotation

specific rotation of the pure enantiomer

excess of a single enantiomer

enantiomeric excess =
entire mixture

45
Isomers with more than one chiral carbon: a maximum of
2n stereoisomers can be obtained
* *
CH3CHCHCH3
Cl OH

Diastereomers are stereoisomers that are not enantiomers

Unlike enantiomers, they have different physical properties, react
46
differently with achiral compounds
Identification of Asymmetric Carbons in
Cyclic Compounds
H
these two groups * H
are different
*
Br
CH3

H H H H
H H CH3 CH3

Br Br Br Br
CH3 CH3 H H

cis-1-bromo-3-methylcyclohexane trans-1-bromo-3-methylcyclohexane

47
 Meso Compounds
Have two or more asymmetric carbons and a plane of
symmetry

They are achiral molecules 48

49
As long as any one conformer of a compound has a
plane of symmetry, the compound will be achiral

plane of
symmetry
plane of
symmetry

Also true for acyclic, we usually check the eclipsed

conformation 50
The R,S nomenclature of isomers with more than one
asymmetric carbon

Enantiomers have opposite configurations at all

asymmetric carbon atoms. Diastereomers have one 51
similar configurationand opposite on the other.
Reactions of compounds that contain an asymmetric
carbon.
CH2CH2CH2Cl CH2CH2CH2OH
H OH- H
CH3CH2 CH3 CH3CH2 CH3

CH CH2 CH2CH3
H2
H H
CH3CH2CH2 Pd/C CH3CH2CH2
CH3 CH3
No reaction at the asymmetric carbon; both the reagent and the
product have the same relative configuration, not always the same
absolute configuration.

If a reaction breaks a bond at the asymmetric carbon, you need to

know the reaction mechanism in order to predict the relative 52
configuration of the product.
 Some Rules to Remember
1. Enantiomers react similarly with achiral compounds
2. Enantiomers react differently with chiral compounds
3. Diastereomers react differently with both chiral and
achiral compounds
4. A reaction that involves non-optically active
reactants, whether achiral or racemic, in which a
new asymmetric carbon is formed, will necessarily
lead to formation of racemic mixtures (optically
inactive).
5. Only when one of the reactants, or a catalyst, are
optically active (chiral with excess of one
enantiomer over the other), a new chiral center that
leads to optical activity may be formed
53
(enantiomeric excess, ee).
 Discrimination of Enantiomers by
Biological Molecules
An enzyme is an example of a stereospecific catalyst

54
A receptor is a protein that binds a certain molecule.
 Discrimination of Enantiomers by
Biological Molecules
CH3 CH3

O O

‫מנטה‬ ‫קימל‬

H3C CH2 H3C CH2

Enantiomers have different

therapeutic properties. Both
enantiomers need to be tested,
preference for the use of the pure
beneficial enantiomer
55