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
 Weve 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 Cyclobutane
HH H H
H C C H
C
H C C H
H C C H
H H H H

Cyclopentane 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

CH2CH3
2.

Cl

8
Solution
Name each of the following:

1. CH3
methylcyclopropane

CH2CH3
2.
1-chloro-3-ethylcyclohexane
Cl

9
Learning Check
What is the IUPAC name for the following molecule?

1. 1-(2-methylbutyl)cyclopentane
2. 2-(3-methylbutyl)cyclopentane
3. 2-(2-methylbutyl)cyclopentane
4. (1,2-dimethylpropyl)cyclopentane
5. (2,2-dimethylpropyl)cyclopentane
Solution
What is the IUPAC name for the following molecule?

1. 1-(2-methylbutyl)cyclopentane
2. 2-(3-methylbutyl)cyclopentane
3. 2-(2-methylbutyl)cyclopentane
4. (1,2-dimethylpropyl)cyclopentane
5. (2,2-dimethylpropyl)cyclopentane
Learning Check
How many secondary hydrogens are there in the
cycloalkane shown below?

1. 2
2. 3
3. 4
4. 5
5. 6
Solution
How many secondary hydrogens are there in the
cycloalkane shown below?

1. 2
2. 3
3. 4
4. 5
5. 6
4.2 Cis-Trans Isomerism in Cycloalkanes
Cycloalkanes are less flexible than open-chain
alkanes
Much less conformational freedom in
cycloalkanes (cant 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
O glucosamine
HO
HO OR
NH2
1. cis, cis
2. trans, trans
3. cis, trans
4. trans, cis
5. 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
O glucosamine
HO
HO OR
NH2
1. cis, cis
2. trans, trans
3. cis, trans
4. trans, cis
5. 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 ring-
puckering

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
Cs 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 CCC 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. torsional
2. steric
3. angle
4. steric and angle
5. torsional and steric
Solution
What kind of strain is relieved the most by
ring puckering in cyclopentane?

1. torsional
2. steric
3. angle
4. steric and angle
5. 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. torsional strain
2. angle strain
3. hydrogen bonding
4. steric strain
5. 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. torsional strain
2. angle strain
3. hydrogen bonding
4. steric strain
5. 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 arent
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 1,2-
dimethylcyclohexane.
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)

OHs 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. a
2. b
3. c
4. d
5. e
Solution

a) b) c) d) e)

Which of the above molecules represents the most stable

conformation of trans-1,3-dimethylcyclohexane?
1. a
2. b
3. c
4. d
5. e
 Learning Check
Which of the following statements is true?

1. An axial group encounters more steric strain than an

equatorial group.
2. All substituted cycloalkanes possess axial and equatorial
bonds.
3. Only cyclopentane rings possess axial and equatorial bonds.
4. Cyclohexane derivatives are more stable with axial
substituents than with equatorial substituents.
5. A cyclic compound cannot contain a double bond.
 Solution
Which of the following statements is true?

1. An axial group encounters more steric strain than an

equatorial group.
2. All substituted cycloalkanes possess axial and equatorial
bonds.
3. Only cyclopentane rings possess axial and equatorial bonds.
4. Cyclohexane derivatives are more stable with axial
substituents than with equatorial substituents.
5. 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-1,3-
dimethylcyclohexane?

1. They are not constitutional isomers.

2. They represent different conformations of the same
molecule.
3. The favored conformer of the 1,3-isomer is more stable than
that of the 1,2-isomer.
4. The favored conformer of the 1,3-isomer and that of the 1,2-
isomer are equal in energy.
5. 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-1,3-
dimethylcyclohexane?

1. They are not constitutional isomers.

2. They represent different conformations of the same
molecule.
3. The favored conformer of the 1,3-isomer is more stable than
that of the 1,2-isomer.
4. The favored conformer of the 1,3-isomer and that of the 1,2-
isomer are equal in energy.
5. 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 Cl

H H
1. 1-axial; 3-axial H H
2. 1-equatorial; 4-equatorial
3. 1-equatorial; 3-equatorial
4. 1-equatorial; 3-axial
5. 1-equatorial; 4-axial
 Solution
What isomer of dichlorocyclohexane is represented
by the Newman projection shown below?
Cl H
H Cl

H H
1. 1-axial; 3-axial H H
2. 1-equatorial; 4-equatorial
3. 1-equatorial; 3-equatorial
4. 1-equatorial; 3-axial
5. 1-equatorial; 4-axial
Learning Check

a) b) c) d) e)

Which of the above structures represents the most stable

conformation of 1-tert-butyl-3,5-dimethylcyclohexane?
1. a
2. b
3. c
4. d
5. e
Solution

a) b) c) d) e)

Which of the above structures represents the most stable

conformation of 1-tert-butyl-3,5-dimethylcyclohexane?
1. a
2. b
3. c
4. d
5. e
Learning Check
What is the energy difference between the two chair
conformations of trans-1,2-dimethylcyclohexane?

1. zero
2. one gauche interaction
3. two gauche interactions
4. three gauche interactions
5. four gauche interactions
Solution
What is the energy difference between the two chair
conformations of trans-1,2-dimethylcyclohexane?

1. zero
2. one gauche interaction
3. two gauche interactions
4. three gauche interactions
5. 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. nothing, it stays where it was

2. it flips to an alternative position on the same carbon
3. it moves to the next carbon
4. the carbon to which the substituent is attached changes
hybridization
5. 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. nothing, it stays where it was

2. it flips to an alternative position on the same carbon
3. it moves to the next carbon
4. the carbon to which the substituent is attached changes
hybridization
5. 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. 1,2-dibromoethane
2. trans-1,2-dibromocyclohexane
3. cis-1,2-dibromocyclohexane
4. cis-1,4-dibromocyclohexane
5. 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. 1,2-dibromoethane
2. trans-1,2-dibromocyclohexane
3. cis-1,2-dibromocyclohexane
4. cis-1,4-dibromocyclohexane
5. 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. a
2. b
3. c
4. d
5. e
Solution

a) b) c) d) e)

Which of the above will have the highest energy after

the chair flip?
1. a
2. b
3. c
4. d
5. 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
11 17
19 13
CH3 H 16
1 9 14 Cholesterol
2 15
10 8
H H
7
HO 3 5
4 6

p. 136
 OH

O
CH3
HO OH
CH3

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 R
H3C
H
1. cis, cis, cis
2. cis, cis, trans H H
3. cis, trans, trans
4. trans. cis, cis H
5. trans, trans, cis
Solution
What are the relative geometries of ring
fusions (starting from the left) for the steroid
shown below?
H3C R
H3C
H
1. cis, cis, cis
2. cis, cis, trans H H
3. cis, trans, trans
4. trans. cis, cis H
5. trans, trans, cis