4. Organic Compounds:
Cycloalkanes and their
Stereochemistry
Why this chapter?
Because cyclic molecules are commonly encountered
in all classes of biomolecules:
-Proteins
-Lipids
-Carbohydrates
-Nucleic
acids
We’ve discussed open-chained compounds up to this point
 Most organic compounds contain rings of carbon atoms
e.g.
- Prostaglandins

-
Steroids
2
Cycloalkanes
Cycloalkanes
 Are cyclic alkanes.
 Have 2H fewer than the open chain. (CnH2n)
 Are named by using the prefix cyclo- before
the name of the alkane chain with the same
number of carbon atoms.
3
4.1 Naming Cycloalkanes


Cycloalkanes are saturated cyclic hydrocarbons
Have the general formula (CnH2n)
4
Cycloalkanes
The structural formulas of cycloalkanes are usually
represented by geometric figures,
Cyclopropane
HH
C
H C
H
C H
H
Cyclopentane
Cyclobutane
H
H C
H
C H
H C
H
C H
H
Cyclohexane
5
Naming Cycloalkanes


Find the parent. # of carbons in the ring.
Number the substituents
6
Naming Cycloalkanes
7
Learning Check
Name each of the following:
1.
CH3
CH2─CH3
2.
Cl
8
Solution
Name each of the following:
1.
CH3
methylcyclopropane
CH2─CH3
2.
1-chloro-3-ethylcyclohexane
Cl
9
Learning Check
What is the IUPAC name for the following molecule?
1.
2.
3.
4.
5.
1-(2-methylbutyl)cyclopentane
2-(3-methylbutyl)cyclopentane
2-(2-methylbutyl)cyclopentane
(1,2-dimethylpropyl)cyclopentane
(2,2-dimethylpropyl)cyclopentane
Solution
What is the IUPAC name for the following molecule?
1.
2.
3.
4.
5.
1-(2-methylbutyl)cyclopentane
2-(3-methylbutyl)cyclopentane
2-(2-methylbutyl)cyclopentane
(1,2-dimethylpropyl)cyclopentane
(2,2-dimethylpropyl)cyclopentane
Learning Check
How many secondary hydrogens are there in the
cycloalkane shown below?
1.
2.
3.
4.
5.
2
3
4
5
6
Solution
How many secondary hydrogens are there in the
cycloalkane shown below?
1.
2.
3.
4.
5.
2
3
4
5
6
4.2 Cis-Trans Isomerism in Cycloalkanes
Cycloalkanes are less flexible than open-chain
alkanes
 Much less conformational freedom in
cycloalkanes (can’t rotate around single bonds)

14
Cis-Trans Isomerism in Cycloalkanes

-
Because of their cyclic structure, cycloalkanes have 2 faces as
viewed edge-on
“top” face
“bottom” face
Therefore, isomerism is possible in substituted cycloalkanes
There are two different 1,2-dimethyl-cyclopropane isomers
15
Stereoisomerism

Compounds which have their atoms
connected in the same order but differ in
3-D orientation
16
Learning Check
Glucosamine (R = H), a naturally occurring substance found in the
exoskeleta of marine invertebrates, is believed by some to be helpful in
relieving arthritic symptoms in humans. What are, respectively, the
relative positions of the amino group to the CH2OH substituent and OR
group?
OH
HO
HO
1.
2.
3.
4.
5.
O
glucosamine
OR
NH2
cis, cis
trans, trans
cis, trans
trans, cis
cannot be determined from this kind of perspective drawing
Solution
Glucosamine (R = H), a naturally occurring substance found in the
exoskeleta of marine invertebrates, is believed by some to be helpful in
relieving arthritic symptoms in humans. What are, respectively, the
relative positions of the amino group to the CH2OH substituent and OR
group?
OH
HO
HO
1.
2.
3.
4.
5.
O
glucosamine
OR
NH2
cis, cis
trans, trans
cis, trans
trans, cis
cannot be determined from this kind of perspective drawing
4.3 Stability of Cycloalkanes: Ring Strain

Rings larger than 3 atoms are not flat

Cyclic molecules can assume nonplanar conformations
to minimize angle strain and torsional strain by ringpuckering

Larger rings have many more possible conformations than
smaller rings and are more difficult to analyze
Stability of Cycloalkanes: The Baeyer
Strain Theory


Baeyer (1885): since
carbon prefers to
have bond angles of
approximately 109°,
ring sizes other than
five and six may be
too strained to exist
Rings from 3 to 30
C’s do exist but are
strained due to bond
bending distortions
and steric
interactions
20
Summary: Types of Strain

Angle strain - expansion or compression of bond
angles away from most stable

Torsional strain - eclipsing of bonds on neighboring
atoms

Steric strain - repulsive interactions between
nonbonded atoms in close proximity
21
4.4 Conformations of Cycloalkanes
Cyclopropane




3-membered ring must have planar structure
Symmetrical with C–C–C bond angles of 60°
Requires that sp3 based bonds are bent (and weakened)
All C-H bonds are eclipsed
22
Bent Bonds of Cyclopropane

In cyclopropane, the C-C bond is displaced
outward from internuclear axis
23
Cyclobutane


Cyclobutane has less angle strain than cyclopropane but
more torsional strain because of its larger number of ring
hydrogens
Cyclobutane is slightly bent out of plane - one carbon
atom is about 25° above
◦ The bend increases angle strain but decreases torsional strain
24
Cyclopentane
Planar cyclopentane would have no angle strain but very
high torsional strain
 Actual conformations of cyclopentane are nonplanar,
reducing torsional strain
 Four carbon atoms are in a plane

◦ The fifth carbon atom is above or below the plane – looks
like an envelope
25
Learning Check
What kind of strain is relieved the most by
ring puckering in cyclopentane?
1.
2.
3.
4.
5.
torsional
steric
angle
steric and angle
torsional and steric
Solution
What kind of strain is relieved the most by
ring puckering in cyclopentane?
1.
2.
3.
4.
5.
torsional
steric
angle
steric and angle
torsional and steric
4.5 Conformations of Cyclohexane




Substituted cyclohexanes occur widely in nature
The cyclohexane ring is free of angle strain and torsional
strain
The conformation is has alternating atoms in a common
plane and tetrahedral angles between all carbons
This is called a chair conformation
28
How to Draw Cyclohexane
29
4.6 Axial and Equatorial Bonds in Cyclohexane
The chair conformation has two kinds of positions for
substituents on the ring: axial positions and equatorial
positions
 Chair cyclohexane has six axial hydrogens perpendicular
to the ring (parallel to the ring axis) and six equatorial
hydrogens near the plane of the ring

30
Axial and Equatorial Positions
Each carbon atom in cyclohexane has one axial
and one equatorial hydrogen
 Each face of the ring has three axial and three
equatorial hydrogens in an alternating
arrangement

31
Drawing the Axial and Equatorial
Hydrogens
32
Conformational Mobility of Cyclohexane

Chair conformations readily interconvert,
resulting in the exchange of axial and equatorial
positions by a ring-flip
33
Learning Check
Which of the following does not contribute
to the overall energy of a cycloalkane?
1.
2.
3.
4.
5.
torsional strain
angle strain
hydrogen bonding
steric strain
All of these contribute to the overall energy of
a cycloalkane.
Solution
Which of the following does not contribute
to the overall energy of a cycloalkane?
1.
2.
3.
4.
5.
torsional strain
angle strain
hydrogen bonding
steric strain
All of these contribute to the overall energy of
a cycloalkane.
4.7 Conformations of Monosubstituted
Cyclohexanes



Cyclohexane ring
rapidly flips between
chair conformations at
room temp.
Two conformations of
monosubstituted
cyclohexane aren’t
equally stable.
The equatorial
conformer of methyl
cyclohexane is more
stable than the axial by
7.6 kJ/mol
36
1,3-Diaxial Interactions


Difference between axial and equatorial conformers is due to steric strain
caused by 1,3-diaxial interactions
Hydrogen atoms of the axial methyl group on C1 are too close to the
axial hydrogens three carbons away on C3 and C5, resulting in 7.6 kJ/mol
of steric strain
2 x 3.8 = 7.6
37
Relationship to Gauche Butane Interactions



Gauche butane is less stable than anti butane by 3.8 kJ/mol
because of steric interference between hydrogen atoms on
the two methyl groups
The four-carbon fragment of axial methylcyclohexane and
gauche butane have the same steric interaction
In general, equatorial positions give more stable isomer
38
4.8 Conformational Analysis of Disubstituted
Cyclohexanes



In disubstituted
cyclohexanes the
steric effects of both
substituents must be
taken into account in
both conformations
There are two
isomers of 1,2dimethylcyclohexane.
cis and trans
In the cis isomer,
both methyl groups
are on the same face
of the ring, and
compound can exist
in two chair
conformations
39
Cis 1,2-Dimethylcyclohexane


Consider the sum of all interactions
In cis-1,2, both conformations are equal in energy
2 x 3.8 = 7.6
3.8
= 11.4 kJ
2 x 3.8 = 7.6
3.8
= 11.4 kJ
Trans-1,2-Dimethylcyclohexane



Methyl groups are on
opposite faces of the
ring
One trans
conformation has both
methyl groups
equatorial and only a
gauche butane
interaction between
methyls (3.8 kJ/mol)
and no 1,3-diaxial
interactions
The ring-flipped
conformation has both
methyl groups axial
with four 1,3-diaxial
interactions
41
Trans-1,2-Dimethylcyclohexane


Steric strain of 4  3.8 kJ/mol = 15.2 kJ/mol makes the diaxial
conformation 11.4 kJ/mol less favorable than the diequatorial
conformation
trans-1,2-dimethylcyclohexane will exist almost exclusively (>99%) in the
diequatorial conformation
3.8
2 x 3.8 = 7.6
= 15.2 kJ
2 x 3.8 = 7.6
42
Table 4-1, p. 124
Cis-1-t-butyl-4-chlorocyclohexane
2 x 1.0 = 2.0
2 x 11.4 = 22.8
44
(Haworth Projection)
OH’s preferred Equatorial
p. 126
Learning Check
a)
b)
c)
d)
e)
Which of the above molecules represents the most stable
conformation of trans-1,3-dimethylcyclohexane?
1.
2.
3.
4.
5.
a
b
c
d
e
Solution
a)
b)
c)
d)
e)
Which of the above molecules represents the most stable
conformation of trans-1,3-dimethylcyclohexane?
1.
2.
3.
4.
5.
a
b
c
d
e
Learning Check
Which of the following statements is true?
1.
2.
3.
4.
5.
An axial group encounters more steric strain than an
equatorial group.
All substituted cycloalkanes possess axial and equatorial
bonds.
Only cyclopentane rings possess axial and equatorial bonds.
Cyclohexane derivatives are more stable with axial
substituents than with equatorial substituents.
A cyclic compound cannot contain a double bond.
Solution
Which of the following statements is true?
1.
2.
3.
4.
5.
An axial group encounters more steric strain than an
equatorial group.
All substituted cycloalkanes possess axial and equatorial
bonds.
Only cyclopentane rings possess axial and equatorial bonds.
Cyclohexane derivatives are more stable with axial
substituents than with equatorial substituents.
A cyclic compound cannot contain a double bond.
Learning Check
Which of the following statements is true concerning
the isomers cis-1,2-dimethylcyclohexane and cis-1,3dimethylcyclohexane?
1.
2.
3.
4.
5.
They are not constitutional isomers.
They represent different conformations of the same
molecule.
The favored conformer of the 1,3-isomer is more stable than
that of the 1,2-isomer.
The favored conformer of the 1,3-isomer and that of the 1,2isomer are equal in energy.
The relative stability of the two molecules cannot be
determined.
Solution
Which of the following statements is true concerning
the isomers cis-1,2-dimethylcyclohexane and cis-1,3dimethylcyclohexane?
1.
2.
3.
4.
5.
They are not constitutional isomers.
They represent different conformations of the same
molecule.
The favored conformer of the 1,3-isomer is more stable than
that of the 1,2-isomer.
The favored conformer of the 1,3-isomer and that of the 1,2isomer are equal in energy.
The relative stability of the two molecules cannot be
determined.
Learning Check
What isomer of dichlorocyclohexane is represented
by the Newman projection shown below?
Cl
H
H
H
1.
2.
3.
4.
5.
1-axial; 3-axial
1-equatorial; 4-equatorial
1-equatorial; 3-equatorial
1-equatorial; 3-axial
1-equatorial; 4-axial
Cl
H
H
H
Solution
What isomer of dichlorocyclohexane is represented
by the Newman projection shown below?
Cl
H
H
H
1.
2.
3.
4.
5.
1-axial; 3-axial
1-equatorial; 4-equatorial
1-equatorial; 3-equatorial
1-equatorial; 3-axial
1-equatorial; 4-axial
Cl
H
H
H
Learning Check
a)
b)
c)
d)
Which of the above structures represents the most stable
conformation of 1-tert-butyl-3,5-dimethylcyclohexane?
1.
2.
3.
4.
5.
a
b
c
d
e
e)
Solution
a)
b)
c)
d)
Which of the above structures represents the most stable
conformation of 1-tert-butyl-3,5-dimethylcyclohexane?
1.
2.
3.
4.
5.
a
b
c
d
e
e)
Learning Check
What is the energy difference between the two chair
conformations of trans-1,2-dimethylcyclohexane?
1.
2.
3.
4.
5.
zero
one gauche interaction
two gauche interactions
three gauche interactions
four gauche interactions
Solution
What is the energy difference between the two chair
conformations of trans-1,2-dimethylcyclohexane?
1.
2.
3.
4.
5.
zero
one gauche interaction
two gauche interactions
three gauche interactions
four gauche interactions
Learning Check
What happens to a substituent in a chair
conformation of cyclohexane when all bonds rotate
in a synchronized fashion?
1.
2.
3.
4.
5.
nothing, it stays where it was
it “flips” to an alternative position on the same carbon
it moves to the next carbon
the carbon to which the substituent is attached changes
hybridization
it moves from a cis to a trans position
Solution
What happens to a substituent in a chair
conformation of cyclohexane when all bonds rotate
in a synchronized fashion?
1.
2.
3.
4.
5.
nothing, it stays where it was
it “flips” to an alternative position on the same carbon
it moves to the next carbon
the carbon to which the substituent is attached changes
hybridization
it moves from a cis to a trans position
Learning Check
Dipole moments usually are measured on collections of
molecules, and represent average values for all
conformations present. Which of the following collections
of molecules will not show a dipole moment?
1.
2.
3.
4.
5.
1,2-dibromoethane
trans-1,2-dibromocyclohexane
cis-1,2-dibromocyclohexane
cis-1,4-dibromocyclohexane
trans-1,4-dibromocyclohexane
Solution
Dipole moments usually are measured on collections of
molecules, and represent average values for all
conformations present. Which of the following collections
of molecules will not show a dipole moment?
1.
2.
3.
4.
5.
1,2-dibromoethane
trans-1,2-dibromocyclohexane
cis-1,2-dibromocyclohexane
cis-1,4-dibromocyclohexane
trans-1,4-dibromocyclohexane
Learning Check
a)
b)
c)
d)
e)
Which of the above will have the highest energy after
the chair flip?
1.
2.
3.
4.
5.
a
b
c
d
e
Solution
a)
b)
c)
d)
e)
Which of the above will have the highest energy after
the chair flip?
1.
2.
3.
4.
5.
a
b
c
d
e
4.9 Conformations of Polycyclic Molecules
Decalin consists of two cyclohexane rings joined to share
two carbon atoms (the bridgehead carbons, C1 and C6)
and a common bond
 Two isomeric forms of decalin: trans fused or cis fused
 In cis-decalin hydrogen atoms at the bridgehead carbons
are on the same face of the rings
 In trans-decalin, the bridgehead hydrogens are on opposite
faces
 Both compounds can be represented using chair
cyclohexane conformations
 Flips and rotations do not interconvert cis and trans

64
65
Fig. 4-17, p. 128
Steroids
18
12
CH3
17
11
19
1
2
HO
CH3
10
3
4
9
H
5
H
13
16
14
8
Cholesterol
15
H
7
6
p. 136
OH
HO
CH3
O
OH
CH3
O
p. 129
p. 129
p. 129
p. 135
Learning Check
What are the relative geometries of ring
fusions (starting from the left) for the steroid
shown below?
H3C
H3C
1.
2.
3.
4.
5.
cis, cis, cis
cis, cis, trans
cis, trans, trans
trans. cis, cis
trans, trans, cis
H
H
H
H
R
Solution
What are the relative geometries of ring
fusions (starting from the left) for the steroid
shown below?
H3C
H3C
1.
2.
3.
4.
5.
cis, cis, cis
cis, cis, trans
cis, trans, trans
trans. cis, cis
trans, trans, cis
H
H
H
H
R