Chapter 4
Introduction
• Stereochemistry
• It is the systematic study of the threedimensional shapes of molecules and
properties that arise from these shapes
• The three-dimensional shapes of molecules
result from many forces
• Conformations are different shapes that a
molecule may assume.
• Conformers are conformational isomers.
• They are in equilibrium at room temperature.
• They can’t usually be isolated because they
interconvert too rapidly
• Alkanes
• have C-C single bonds formed by s overlap of
sp3 hybrid orbitals
• Rotation is possible around s bonds because of
their cylindrical symmetry => Many Conformers
I. Conformations
A.
Ethane
B.
Propane
C.
Butane
A. Ethane
• Conformers interconvert rapidly and a structure
is an average of conformers
• Representing three dimensional conformers in two
dimensions is done with standard types of drawings
• Molecular models are
three dimensional
objects that enable us
to visualize conformers
Representing Conformations
There are two representations:
• Sawhorse representation
• Newman projection
Representing Conformations
• Sawhorse representations
show molecules at an angle,
showing a molecular model
– C-C bonds are at an angle
to the edge of the page
– all C-H bonds are shown
• Newman projections show
how the C-C bond would
project end-on onto the
paper
– Bonds to front carbon are
lines going to the center
– Bonds to rear carbon are
lines going to the edge of
the circle
Ethane’s Conformations
• The most stable conformation of ethane has all six C–
H bonds away from each other (staggered).
• The least stable conformation has all six C–H bonds
as close as possible (eclipsed) in a Newman
projection.
Ethane’s Conformations
• The barrier to rotation between conformations is small
(12 kJ/mol; 2.9 kcal/mol)
• The eclipsed conformers are 12 kJ/mol higher in
energy than the staggered conformers – energy due
to torsional strain
Ethane’s Conformations
• The torsional strain (12 kJ/mol) of the eclipsed
conformers are due to 3 H-H eclipsing interactions.
• Each H-H interaction contributes 4.0 kJ/mol
B.
Propane
• Propane (C3H8) has
torsional barrier around
the carbon–carbon
bonds (14 kJ/mol).
• Eclipsed conformer of
propane has two
ethane-type H–H
interactions and an
interaction between C–
H and C–C bond
• The torsional strain (14 kJ/mol) of the eclipsed
conformers are due to 2 ethane-type H-H interactions
and an interaction between C–H and C–C bond.
• The C–H and C–C bond interaction contributes
6.0 kJ/mol (= 14 – (2 x 4.0))
Practice Problem: Make a graph of potential energy versus
angle of bond rotation for propane, and
assign values to the energy maxima
Practice Problem: Draw Newman projections of the most stable
and least stable conformations of
bromoethane
C.
Butane
• As the alkane becomes larger, the conformations
become more complex.
• Butane has eclipsed and staggered conformers
with different energy level around C2-C3:
Butane’s Conformations
• anti conformation is the most stable conformation
of butane
• It has two methyl groups 180° away from each other
Butane’s Conformations
• Rotation around the C2–C3 gives eclipsed
conformation
Butane’s Conformations
• gauche conformation is the staggered conformation
with methyl groups 60° apart.
• Although it has no eclipsing interactions, it is 3.8 kJ/mol higher in
energy than the anti conformation.
• This is due to steric strain.
Butane’s Conformations
• The steric strain (3.8 kJ/mol) of the gauche
conformation is due to the repulsive interaction that
occurs when atoms are forced together than their
atomic radii allow.
Butane’s Conformations
• The least stable eclipsed conformation is one
in which the methyl groups are too close.
• 19 kJ/mol is due to steric and torsional strain.
For any alkane, the most favorable conformation is:
the staggered arrangement on C-C bonds and
large substituents arranged anti to one another.
One particular conformer is
more stable than another
means a large percentage
of molecules will be found a
in more stable conformation
than in a less stable one.
Practice Problem: Consider 2-methylpropane (isobutane).
Sighting along the C2-C1 bond:
a. Draw a Newman projection of the most stable
conformation
b. Draw a Newman projection of the least stable
conformation
c. Make a graph of energy versus angle of rotation
around the C2-C1 bond
d. Since a hydrogen-hydrogen eclipsing interaction
costs 4.0 kJ/mol and a hydrogen-methyl eclipsing
interaction costs 6.0 kJ/mol, assign relative
values to the maxima and minima in your graph
Practice Problem: Sight along the C2-C3 bond of 2,3-dimethyl-butane, and draw a Newman projection of
the most stable conformation.
Practice Problem: Draw a Newman projection along the C2-C3
bond of the following conformation of 2,3dimethylbutane, and calculate a total strain
energy
II. Stability of Cycloalkanes
A.
The Baeyer Strain Theory
B.
Heat of Combustion
C.
The Nature of Ring Strain
D.
Cyclopropane: An Orbital View
A. 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.
• Angle strain is the strain introduced in a molecule
when a bond angle deviates from
the ideal tetrahedral value, 109°.
• Rings from 3 to 30 C’s do exist, despite Baeyer’s theory.
B. Heat of Combustion
• Heat of Combustion (DH) – is the amount of
heat released when the compound burns
completely with O2.
• The more strain energy, the higher the DH and the
less stable the alkane
Strain Energy and Heat of Combustion
• The higher the n (# CH2), the higher the DH
• Therefore, one must compare DH/n rather than DH
Strain Energy =
of Cycloalkane
[
n DH/n cycloalkane - DH/n reference alkane
]
Baeyer’s theory is not fully correct
• Cyclopropane and cyclobutane are strained as predicted.
• Cyclopentane is more strained than predicted.
• Cyclohexane is strain-free.
Practice Problem: Figure 4.8 shows that cyclopropane is more
strained than cyclohexane by 115 kJ/mol.
Which has the higher heat of combustion on
a per-gram basis, cyclopropane or
cyclohexane?
C. The Nature of Ring Strain
• Rings larger than 3 atoms are not flat.
• They adopt puckered three-dimensional conformations that allow
bond angles to be nearly tetrahedral
• 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
• Cyclopropane has high torsional strain (in addition
to angle strain).
• This is because C-H bonds on neighboring atoms
are eclipsed.
Summary: Types of Strain
These contribute to the overall energy of a cycloalkane:
• Angle strain – is caused by expansion or
compression of bond angles away from the normal
109o tetrahedral value
• Torsional strain – is caused by eclipsing of bonds on
neighboring atoms
• Steric strain – is caused by repulsive interactions
between nonbonded atoms in close proximity
Practice Problem: Each H-H eclipsing interaction in ethane costs
about 4.0 kJ/mol. How many such interactions
are present interactions are present in
cyclopropane? What fraction of the overall
115 kJ/mol (27.5 kcal/mol) strain energy of
cyclopropane is due to torsional strain?
Practice Problem: cis-1,2-Dimethylcyclopropane has a larger
heat of combustion than trans-1,2dimethylcyclopropane. How can you account
for this difference? Which of the two
compounds is more stable?
D.
Cyclopropane: An Orbital View
• Cyclopropane was first prepared by reaction of
Na with 1,3-dibromopropane:
Cyclopropane
• 3-membered ring must have planar structure
• It is symmetrical with C–C–C bond angles of 60°
• All C-H bonds are eclipsed
Bent Bonds of Cyclopropane
• Cyclopropane requires that sp3 based bonds are
bent
• The orbitals cannot point directly toward each other;
they overlap at a slight angle
• Cyclopropane bonds are weaker and more reactive
Bent Bonds of Cyclopropane
• Structural analysis of cyclopropane shows
that electron density of C-C bond is displaced
outward from internuclear axis
III. Conformations of Cycloalkanes
A.
Cyclobutane
B.
Cyclopentane
A.
Cyclobutane
• Cyclobutane has less angle strain than
cyclopropane but more torsional strain
because of its larger number of ring
hydrogens
Cyclopropane
Cyclobutane
(115 kJ/mol strain)
(110.4 kJ/mol strain)
Cyclobutane
• Cyclobutane is slightly bent out of plane - one
carbon atom is about 25° above
 The bend increases angle strain but decreases
torsional strain
B.
Cyclopentane
• Planar cyclopentane would have no angle
strain but very high torsional strain
• Actual conformations of cyclopentane are
nonplanar, reducing torsional strain
• This increases angle strain.
Cyclopentane
• Four carbon atoms are in a plane
 The fifth carbon atom is above or below the plane –
looks like an envelope
 Most of the H’s are nearly staggered
 This increases angle strain but decreases torsional
strain
Practice Problem: How many H-H eclipsing interactions would
be present if cyclopentane were planar?
Assuming an energy cost of 4.0 kJ/mol or
each eclipsing interaction, how much
torsional strain would planar cyclopentane
have? How much of this strain is relieved by
puckering if the measured total strain of
cyclopentane is 26.0 kJ/mol?
Practice Problem: Two conformations cis-1,3-Dimethylcyclobu-tane are shown. What is the difference
between them, and which do you think is
likely to be more stable?
IV. Conformations of Cyclohexanes
A.
Overview
B.
Axial and Equatorial Bonds in
Cyclohexane
C.
Conformational Mobility of
Cyclohexane
IV. Conformations of Cyclohexanes
D.
Monosubstituted Cyclohexanes
E.
Disubstituted Cyclohexanes
F.
Boat Cyclohexane
A.
Cyclohexane: Overview
• Substituted cyclohexanes occur widely in nature
• The cyclohexane ring is free of angle strain and
torsional strain
Cyclohexane
Cyclohexane has a chair conformation:
 The conformation has alternating atoms in a common
plane and tetrahedral angles (109o) between all
carbons
 All neighboring C-H bonds are staggered
 The ring is strain-free, with neither angle strain nor
torsional strain
How to Draw Cyclohexane
B.
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
• 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
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
Drawing the Axial and Equatorial Hydrogens
C.
Conformational Mobility of
Cyclohexane
• Conformational mobility: Chair conformations
readily interconvert, resulting in the exchange of
axial and equatorial positions by a ring-flip
Ring-flip
• A chair cyclohexane can be ring-flipped by keeping the
middle four carbon atoms in place while folding the two
ends in opposite directions.
• An axial substituent in one chair form becomes an
equatorial substituent in the ring-flipped chair form, and
vice-versa.
Bromocyclohexane
• When bromocyclohexane ring-flips, the bromine’s
position goes from equatorial to axial and so on
• At room temperature the ring-flip is very fast and
the structure is seen as the weighted average
Practice Problem: Draw two different chair conformations of
cyclohexanol (hydroxycyclohexane), showing
all hydrogen atoms. Identify each position as
axial or equatorial.
Practice Problem: Draw two different chair conformations of
trans-1,4-dimethylcyclohexane, and label all
positions as axial or equatorial.
Practice Problem: Identify each of the colored positions – red,
blue, and green – as axial or equatorial.
Then carry out a ring-flip, and show the new
positions occupied by each color.
D.
Monosubstituted Cyclohexanes
• The two conformers of a monosubstituted
cyclohexane are not equal in energy
• A substituent is always more stable in an
equatorial position than in axial position
• The equatorial conformer of methyl cyclohexane
is more stable than the axial by 7.6 kJ/mol.
Energy and Equilibrium
The relative amounts of the two conformers depend
on their difference in energy DE = RT ln K
• R is the gas
constant [8.315
J/(K•mol)]
• T is the Kelvin
temperature
• K is the
equilibrium
constant between
isomers
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
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
(2 x 3.8 kJ/mol)
In general, equatorial positions give more stable isomer
The exact amount of 1,3-diaxial steric strain in a specific
compound depends on the nature and size of the substituent.
Double the value to arrive at the amount of strain in a monosubstiuted cyclohexane
Practice Problem: How can you account for the fact (Table 4.2)
that an axial tert-butyl substituent has much
larger 1,3-diaxial interactions than isopropyl,
but isopropyl is fairly similar to ethyl and
methyl? Use molecular models to help with
your answer.
Practice Problem: Why do you suppose an axial cyano
substituent causes practically no 1,3-diaxial
steric strain (0.4 kJ/mol). Use molecular
models to help with your answer.
Practice Problem: Look at Figure 4.18 and estimate the
percentages of axial and equatorial
conformers present at equilibrium in
bromocyclohexane
E.
Disubstituted Cyclohexanes
• In disubstituted cyclohexanes the steric effects of
both substituents must be taken into account in
both conformations before deciding which
conformation is favored.
• There are two isomers of 1,2 dimethylcyclohexane:
• cis
• trans
Conformational Analysis of 1,2-dimethylcyclohexane
cis-1,2-Dimethylcyclohexane
• In the cis isomer, both
methyl groups are on
the same face of the
ring, and compound
can exist in two chair
conformations
• Consider the sum of all
interactions
• In cis-1,2, both
conformations are equal
in energy
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 1,3diaxial interactions
• The ring-flipped conformation has
both methyl groups axial with four
1,3-diaxial interactions
• 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
Conformational Analysis of 1-Bromo-4-t-butylcyclohexane
• The large amount of steric strain caused by an axial tert-butyl
group holds the cyclohexane ring in a single conformation.
• This allows chemists to study chemical reactivity of immobile
cyclohexane rings.
Axial and Equatorial Relationships among substituents
Practice Problem: Draw the most stable chair conformation of
the following molecules, and estimate the
amount strain in each:
a. trans-1-Chloro-3-methylcyclohexane
b. cis-1-Ethyl-2-methylcyclohexane
c. cis-1-Bromo-4-ethylcyclohexane
d. cis-1-tert-Butyl-4-ethylcyclohexane
Practice Problem: Name the following compound, identify each
substituent as axial or equatorial, and tell
whether the conformation shown is the more
stable or less stable chair form (yellow-green
= Cl)
F.
Boat Cyclohexane
• Cyclohexane can also be
in a boat conformation
– It is also free of angle
strain
– It is less stable than chair
cyclohexane due to steric
and torsional strain
– ~29 kJ/mol (7.0 kcal/mol)
less stable than chair
• C-2, 3, 5, 6 are in a plane
• H on C-1 and C-4
approach each other
closely enough to
produce considerable
steric strain
• Four eclipsed H-pairs on
C- 2, 3, 5, 6 produce
torsional strain
• Boat cyclohexane is ~29 kJ/mol less stable than
chair cyclohexane.
• This value is reduced to about 23 kJ/mol by
twisting slightly, thereby relieving some torsional
strain: Twist boat conformation
Practice Problem: trans-1,3-Di-tert-butylcyclohexane is one of
the few molecules that exists largely in a
twist-boat conformation. Draw both a chair
conformation and the likely twist-boat
conformation, and then explain why the twistboat form is favored.
V. Conformations of Polycyclic
Molecules
A.
Overview
A. Overview
• Decalin consists of two cyclohexane rings joined to
share two carbon atoms (the bridgehead carbons,
C1 and C6) and a common bond
Decalin has two isomeric forms: cis fused or trans 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
• Polycyclic compounds are common, and many
valuable substances have fused-ring structures.
• Like decalin, norborane is a bicycloalkane.
• It has a conformationally locked boat cyclohexane
ring in which carbons 1 and 4 are joined by an
additional CH2 group.
• Substituted norboranes, such as camphor, are
found widely in nature.
Practice Problem: Which isomer is more stable, cis-decalin or
trans-decalin? Explain.
Chapter 4