Ch.

3: Alkanes and Cycloalkanes: Conformations and

cis-trans Stereoisomers
Stereochemistry: three-dimensional aspects of molecules
Conformation: different spatial arrangements of atoms that
result from rotations about single (σ) bonds
Conformer: a specific conformation of a molecule
3.1: Conformational Analysis of Ethane

H
H H
H H H
H H C C
H
H H H

Sawhorse 1
There are two conformations of ethane:
Back
carbon
H
H H

H H
H Front
carbon

Newman projection Staggered Eclipsed

Dihedral (torsion) angle: angle between an atom (group) on the

front atom of a Newman Projection and an atom (group)
on the back atom
Dihedral angles of ethanes:
Staggered conformation: 60° (gauche), 180° (anti),
and 300° (-60°, gauche)
Eclipsed conformation: 0°, 120°, and 240° (-120°)
2
Energy vs. dihedral angle for ethane
http://www2.chem.ucalgary.ca/Flash/ethane.html

The barrier (Eact) for a 120° rotation of ethane (from one staggered
conformer to another) is 12 KJ/mol. The eclipsed conformer is
the barrier to the rotation. An H-H eclipsing interaction = 4 KJ/mol
Torsional Strain: strain (increase in energy) due to eclipsing 3
interactions
Conformations of Propane

H3C
H CH3
H H H
H H C C
H
H H H
staggered

The barrier to C-C rotation for 5.0 KJ/mol

propane is 13 KJ/mol = 1 (CH3-H)
+ 2 (H-H) eclipsing Interactions.
A CH3-H eclipsing interaction
is 5 KJ/mol

eclipsed 4
 3.2: Conformational Analysis of Butane
Two different staggered and eclipsed conformations
Staggered: anti

H3C
H CH3
H H H
H H C C
H
CH 3 H 3C H

Staggered: gauche
3 KJ/mol

H3C
H CH3
H H H 3C
H CH 3 C C
H
H H H 5
Steric Strain: repulsive interaction that occurs when two groups
are closer than their atomic radii allow
3 KJ/mol

Eclipsed conformations of butane: rotational barrier of butane is

25 KJ/mol. A CH3-CH3 eclipsing interaction is 17 KJ/mol.
CH3 - H CH3 - CH3

6
Energy diagram for the rotation of butane

Summary:
H - H eclipsed 4.0 KJ/mol torsional strain
H - CH3 eclipsed 5.0 KJ/mol mostly torsional strain
CH3 - CH3 eclipsed 17 KJ/moltorsional + steric strain
7
CH3 - CH3 gauche 3.0 KJ/mol steric strain
3.3: Conformations of Higher Alkanes - The most stable
conformation of unbranched alkanes has anti relationships
between carbons (extended carbon chain).

3.4 The Shapes of Cycloalkanes: Planar or Nonplanar?

Angle Strain: strain due to deforming a bond angle from its ideal
value (Baeyer Strain Theory)

60° 90° 108° 120° 128° 135°

8
Internal angles of polygons
Heats of Combustion of Cycloalkane: the more strained a compound is,
the more heat it releases upon combustion
CnH2n + O2 n CO2 + (n+1) H2O + heat
cycloalkane (can be measured)

Total Strain Sample _ Reference

= ΔHcomb per -CH2- ΔHcomb per -CH2- •n
Energy

Cycloalkane Ring Size (n) Hcomb KJ/mol Hcomb per CH2- KJ/mol Total Strain Energy

Cyclopropane 3 2091 697 (43) 129

strained
rings
Cyclobutane 4 2721 681 (27) 108

Cyclopentane 5 3291 658 (4) 20

common
rings Cyclohexane 6 3920 654 (0) 0

Cycloheptane 7 4599 657 (3) 21

Cyclooctane 8 5267 658 (4) 32

medium
rings Cyclononane 9 5933 659 (5) 45

Cyclodecane 10 6587 659 (5) 45

large rings
(> 12) Cyclohexadecane 16 10466 654 (0) 0
9
Alkane reference 654 0
With the exception of cyclopropane, cycloalkane are not planar.
3.5 Small Rings: Cyclopropane and Cyclobutane
Bonding in Cyclopropane: reduced overlap of the sp3-hybridized
orbitals

60° 109°

H
H Total strain for cyclopropane
CH2 = angle strain +
torsional strain
HH
10
all adjacent CH2 groups are eclipsed
Cyclobutane - reduced angle and torsional strain relative to
cyclopropane
H H Puckering partially
CH
relieves torsional strain
2

H CH2
H
3.6: Cyclopentane: planar conformation is strain free according
to Baeyer; however, there is considerable torsional strain (10
H-H eclipsing interactions)
Envelope and half-chair conformations relieve much of the
torsional strain

11
3.7: Conformations of Cyclohexane - ΔHcomb suggests that
cyclohexane is strain-free; favored conformation is a chair.
3.8: Axial and Equatorial Bonds in Cyclohexane
Chair cyclohexane has two types of hydrogens:
axial: C-H axis is “perpendicular” to the “plane of the ring”
equatorial: C-H axis is “parallel” to the “plane of the ring”
Chair cyclohexane has two faces; each face has alternating axial
a
and equatorial -H’s e
a

axial
a
e
e
e
e
equatorial
a
e
a
a

12
top face bottom face
All H-H interactions are staggered - no torsional strain; minimal
angle strain (~111°)

Other conformations of cyclohexane:

half chair; twist boat, and boat
3.9: Conformational Inversion (Ring-Flipping) in Cyclohexane
Ring flip interchanges the axial and equatorial positions. The
barrier to a chair-chair interconversion is 45 KJ/mol.

45 KJ/mol

13
Chair-Chair Interconversion of Cyclohexane

axial
equatorial

Half-chair
Chair
(+ 45 KJ/mol)

Twist-boat Twist-boat
Boat
(+23 KJ/mol) (+ 23 KJ/mol)
(+ 32 KJ/mol)

axial
equatorial

Half-chair Chair
14
(+ 45 KJ/mol)
Energy Profile for the Chair-Chair Interconversion of Cyclohexane
http://www2.chem.ucalgary.ca/Flash/cyclohexane.html

half-chair half-chair

boat

chair twist-boat twist-boat chair

15
3.10: Conformational Analysis of Monosubstituted Cyclohexanes
most stable chair conformation has the substituent in the equatorial
position R
Keq
H R
H

R= -CH3 5 : 95
1,3-diaxial
interactions

16
 Methylcyclohexane
equatorial anti butane

Methylcyclohexane gauche butane

axial +3.0 KJ/mol

2 gauche butane interactions: 2 x 3.0 KJ/mol = 6.0 KJ/mol (actual 7.3 KJ/mol)
Axial position is more sterically congested (steric strain) and is therefore
less favored thermodynamically 17
 Keq R

R H

Substituent per 1,3-diaxial total strain energy eq./axial

interaction (KJ/mol) (A-value)
-F 0.5 1.0 60:40
-Cl 1.4 2.8 70:30
-Br 1.4 2.8 70:30
-I 0.85 1.7 65:34
-OH 2.1 4.2 85:15
-NH2 2.7 5.4 90:10
-N(CH3)2 4.4 8.8 97:3
-CH3 3.6 7.3 95:5
-CH2CH3 3.9 7.8 96:4
-CH(CH3)2 4.3 8.6 97:3
-C(CH3)3 >8 16 >> 99.9:0.1
-CH2C(CH3)3 4.2 8.4 97:3
-C6H5 6.3 12.6 99.5:0.5
CO2H 2.9 5.8 92:8
ΔE =-CN 0.4
-RT ln Keq, where 0.8x 10-3
R= 8.3 60:40 T= 300 °K (room temp)
KJ/mol, 18
3.11: Disubstituted Cycloalkanes: Stereoisomers
Stereochemistry: three-dimensional arrangement of atoms
(groups) in space
Isomers: different chemical compounds with the same formula
Constitutional isomers: same formula, but different
connectivity of atoms (or groups)
C5H10

ethylcyclopropane 1,2-dimethylcyclopropane

Stereoisomers: same connectivity, but different spatial

arrangement of atoms or groups
H H H CH3
H3C CH3 H3C H

cis-1,2-dimethylcyclopropane trans-1,2-dimethylcyclopropane
ΔHcomb is ~ 5KJ/mol higher for the cis isomer

trans: on opposite sides of the ring 19

cis: on the same side of the ring
3.12: Conformational Analysis of Disubstituted Cyclohexanes
1,4-dimethylcyclohexane: ΔHcomb is 7 KJ/mol lower for the trans isomer
1,3-dimethylcyclohexane: ΔHcomb is 7 KJ/mol lower for the cis isomer
1,2-dimethylcyclohexane: ΔHcomb is 6 KJ/mol lower for the trans isomer
H CH3 H2 CH3
H CH3
CH3 H H C
H CH3
C H
CH3 H H2 H

cis (one equatorial, one axial)

(2 x 3.0) + 3.0 = 9.0 KJ/mol

H CH3
H2 H H
C CH3 CH3 H H
CH3 H
C CH3 H
H2 H H H CH3

trans (two equatorial, no axial) trans (no equatorial, two axial)

3.0 KJ/mol 2 (2 x 3.0) = 12.0 KJ/mol
DG = 9.0 KJ/mol Keq = ~ 98:2

20
 1,3-dimethylcyclohexane 1,4-dimethylcyclohexane

H H
H H
CH3 CH3
H CH3 H3C
CH3 H H3C
H3C H CH3
cis
H
trans cis trans
(two equatorial) (one equatorial, one axial) (one equatorial, one axial) (two equatorial)

H CH3
H H3C H3C
H H H
CH3 H H H
CH3 CH3
CH3 CH3
cis trans cis
(two axial) (one equatorial, one axial) trans
(one equatorial, one axial) (two axial)

3.13: Medium and Large Rings (please read)

21
3.14: Polycyclic Ring Systems - contains more than one ring
fused - two rings share a pair of bonded atoms
spirocyclic - one atom common to two rings
bridged bicyclic - nonadjacent atoms common to two rings

fused spiro bridged

H H

H H
H

H H
trans-decalin cis-decalin
cis- and trans-decalin are stereoisomers, they do not interconvert 22
into each other
Cholesterol H3C H3C
H CH3 H
H3C H
HO
H H
HO H

3.15: Heterocyclic Compounds (please read)

a cyclic compound that contains an atom other than carbon in
the ring (typically N, O, S)
Drawing Structures
CYCLIC ALKANES: Substituents on a cycloalkane can be cis or trans to
each other. You should draw the ring in the plane of the paper (solid lines)
and use dashes and wedges to show whether substitutents are above or
below the plane of the ring.

correct ••
incorrect ••

cis trans

On occasion you may wish to distinguish the faces of a cycloalkane.

top face
a
a a
a a
b
b b
b b
bottom face 24
 Atropisomers

Atropisomers are stereoisomers arising because of hindered

rotation about a single bond, where energy differences due
to steric strain or other contributors create a barrier to
rotation that is high enough to allow for isolation of
individual conformers

Atropisomers of 6,6'-
dinitro-2,2'-diphenic
acid, first experimentally
described case, by
Christie and Kenner
(1922)

25
Determining the axial stereochemistry of biaryl atropisomers
can be accomplished through the use of a Newman
projection along the axis of hindered rotation.

The ortho, and in some cases meta substituents are first

assigned priority based on Cahn–Ingold–Prelog priority rules.
Starting with the substituent of highest priority in the closest
ring and moving along the shortest path to the substituent of
highest priority in the other ring, the absolute configuration is
assigned P for clockwise and M for counterclockwise. In the
example shown, A has priority over B

26
 Natural products, drug design

Many atropisomers occur

in nature. Some natural
products can be used as
drugs and an example of
this is mastigophorene A.
Mastigophorene A has
been found to aid in nerve
growth

27