Cyclohexane

Conformations
 The “Flat” Conformation Of Cyclohexane
Flat cyclohexane is very strained (about 20 kcal/mol). Not
only is there angle strain (with internal angles at 120°,
above the ideal angle of 109°) but every C-C bond is
eclipsed, so there is also tremendous torsional strain. In
solution, the flat conformation of cyclohexane is generally
of too high an energy to be observed.
 The “Half Chair” Conformation Of Cyclohexane
If one takes one end of the cyclohexane and “pulls” it up, then we will have a
“half-chair” conformation of cyclohexane. If you try this with a model you
will note that there will be rotations about 4 different C-C bonds, and this will
result in them no longer being completely eclipsed. Furthermore the bond
angles upon doing so will more closely resemble the ideal tetrahedral bond
angles of 109°.

This results in significantly less torsional strain and angle strain. The strain
energy relative to a theoretical “unstrained” ring is about 10.8 kcal/mol.
 The “BOAT” Conformation of Cyclohexane
Taking the other end of the half-chair and pulling it up
creates a structure which resembles a boat (or, as I modestly
propose, a hammock). There is no longer significant angle
strain, since all internal angles can now be 109 degrees.
There is still torsional strain, however, as if you look
carefully you will see that along two different C-C bonds,
the C-H bonds are all eclipsed [there’s a total of 4 eclipsing
H-H interactions].
Furthermore, there is an additional source of strain in the
hydrogens of the “prows” of the boat.
In the boat conformation these hydrogens are held together in
such close proximity that their electron clouds come close
enough together to repel, an effect known as Van Der Waals
strain.
Sometimes this interaction is known as the “flagpole”
interaction. The ring strain in the boat is about 7.0 kcal/mol.
The “Twist Boat” Conformation Of Cyclohexane
. A significant portion of Van Der Waals strain of the boat can
be relieved by a slight rotation of the bonds, resulting in a
conformation known as the “twist boat”.
Drawings don’t do it adequate justice – for this one you really
need to build a model to see how a slight twisting of the
structure can result in less strain. There is still significant
torsional strain since there are two C-C bonds about which the
hydrogens are not perfectly staggered.
 The “Chair” Conformation Of Cyclohexane
If one starts with the “half chair” and then pulls the “flat” end
in the opposite direction of the carbon that is poking out of the
plane, the result is a structure with 4 carbons in the same plane
and one carbon each poking above and below the plane. This
resembles a deck chair, so it goes by this name.
• The chair is a perfectly unstrained molecule. There are no
eclipsing interactions; the conformation along each C-C
bond is staggered.
• Furthermore the orientations of the atoms about each carbon
are perfectly tetrahedral. Since it lacks ring strain and is of
lowest energy, the chair conformation is the dominant
conformation that cyclohexane will be found in solution.

The chair conformation is the most important

conformation of cyclohexane to understand.
Energy Diagram: The 5 Key Conformations Of
Cyclohexane
Putting all of these conformations together, we can obtain this
chart, with highest energy at the top:
 A Newman Projection Of The Cyclohexane Chair

Newman projection of the cyclohexane chair conformation. Notice

how the orientation about each C-C bond is staggered

This is an important clue as to the stability of this conformation:

unlike other conformations of cyclohexane, the orientation about
each C–C bond is staggered, which means that torsional strain is
minimized.
Groups Pointing Straight Up And Straight Down Are In The
“Axial” Position
First, do you see how some groups point straight up and
straight down? Those are called the “axial” groups. See how
axial alternates, up-down-up-down-up-down (12 o’clock to 6
o’clock and back again).
Groups Pointing Off To The Side Are In The “Equatorial” Position
Then, there are groups which point off to the side. We call these the
“equatorial” groups, as they are in line with certain of the bonds of the
ring. They alternate from “somewhat up” (10 o’clock and 2 o’clock, if
you use a clock face analogy) to “somewhat down” (8 o’clock and 4
o’clock).
Important Point: Equatorial Groups Can Be “Up” And “Down”
Too
Here’s the thing. Each carbon has one “up” group and one “down” group, and
also one “axial” group and one “equatorial” group. So if a carbon is attached to
a group that is “axial up”, the down group must be equatorial. Likewise a
carbon attached to an “axial down” group must have an “up” group that is
equatorial.

It took awhile for me to appreciate that equatorial groups can be “up” and
“down” too – even though they don’t point “straight” up and down.
Let’s go back to the “top” view of the cyclohexane. The groups which are
“up” will be coming “towards” us in the page – wedges , in other words,
since we’re looking from the top down. The groups which are “down” will
be pointing away from us (dashes). First, let’s take that top view of
cyclohexane and put dots where the axial groups are (they’re either
pointing towards us [pink] or away from us [yellow]). And let’s colour the
bonds to the equatorial group whether they point towards us (green) or
away from us (blue).

Here’s the “top down” picture, colour coded for attempted clarity, and
arbitrarily calling the carbon at the top “Carbon #1” and numbering
clockwise.
Mapping Out “Axial Up”, “Axial Down”,
“Equatorial Up”, “Equatorial Down” On A
Cyclohexane Chair
The Two Chair Conformations Of 1-Methyl
Cyclohexane
The Cyclohexane Chair Flip Energy Diagram
The Energy Barrier For A Cyclohexane Chair Flip
Is Small Enough To Allow The Two
Conformations To Interconvert At Room
Temperature

For example, let’s take 1-methylcyclohexane.

Let’s say we start with the chair on the left
(methyl is axial) and a chair flip converts it
into the chair on the right (methyl is
equatorial).

First of all, note that these are NOT mirror

images of each other – they are different
conformations.
Being quite rigid molecules, you would expect “axial” 1-
methylcyclohexane to have slightly different properties than
“equatorial” 1-methylcyclohexane.

If you could isolate the “axial” conformer, for instance, you’d

expect it to have a slightly different melting point and boiling point
than the “equatorial” conformer, since the molecules will stack
differently with each other.

Furthermore, with other cyclohexanes, the axial and equatorial

conformers even have different reactivity
 Substituted Cyclohexanes – Axial vs
Equatorial
1. Brief Review On The Cyclohexane Chair Conformation
•Cyclohexane Undergoes A Conformational Interconversion Known As
A Chair Flip. In this chair flip, all axial groups become equatorial, and
all equatorial groups become axial. [but all “up” groups remain up, and
all “down” groups remain down].
•The two chair forms of cyclohexane itself are completely
indistinguishable, but this is not true in most cases. For example, in 1-
methylcyclohexane, one chair conformer has an axial methyl group, and in
the other the methyl group is equatorial. These are conformational isomers,
or simply, “conformers”.
•At room temperature, these two conformations are in rapid equilibrium with each other.
There is an activation barrier of about 10 kcal/mol for this interconversion, since the high-
energy “half-chair” conformer is an intermediate in this process. Trying to observe both
conformations of 1-methylcyclohexane at room temperature with a device for taking
“molecular snapshots” (an NMR spectrometer is what we use – more precise details on this
in future posts) results in a blurred picture. Like an old camera trying to take pictures of
spokes on a moving bicycle wheel, the “shutter speed” is too slow, and the result is that the
images blend together to give an average. Using this device, it’s simply not possible to see
both cyclohexane conformers of 1-methylcyclohexane at room temperature.
•At very low temperatures (about 80 degrees above absolute zero) equilibrium between the
two chair forms stops, because there isn’t enough thermal energy available to ascend the
activation barrier of 10 kcal/mol.
In 1-Methylcyclohexane, The
Ratio of the Equatorial Methyl
Conformer to the Axial Methyl
Conformer Is 95:5

Very interesting! This must mean that the

equatorial conformation is of lower energy
than the “axial” conformation.
The “Equatorial” Methyl Conformation Encounters Fewer
Gauche Interactions Than the Axial Methyl Conformation
Let’s look at the Newman projection of the chair. Imagine looking
along the C-1 to C-2 bond (which is coplanar with the C-4 to C-5
bond). Here’s what you’d see.
Note that in the conformation where methyl is axial, there is a gauche
interaction between the axial methyl group and C-3. This is absent in the
conformation where methyl is equatorial. This gauche interaction is an
example of van der Waals strain, which is what makes the axial conformer
higher in energy.

There is actually a second gauche interaction if you look along C-1 to C-6 .
This gauche interaction is with C-5.
A simple way to keep track is to think of it as the methyl group interacting
with the other ‘axial’ hydrogens, at C-3 and C-5. These are called “diaxial
interactions” since they are steric interactions between axial substituents.

Bottom line: in two unequal conformations of a

cyclohexane ring, the conformation where
steric interactions are minimized will be
favoured.
The Experimentally Determined Equilibrium Ratio Of
Conformers Can Be Used To Calculate The Energy
Difference
Now here’s a neat consequence of this knowledge. Since this ratio of conformers
(95:5) represents a system at equilibrium, we can actually use it to calculate the
difference in energy of these two conformers using the following equation:

arrhenius-equation-shows-relationship-between-equiibrium-constant-and-
activation-energy

For a 50:50 mixture (K = 1) the energy difference ΔG would be zero.

For methylcyclohexane at room temperature (298 K) the 95:5 ratio of

equatorial to axial conformers translates to an energy difference of 1.70
kcal/mol.

In other words, the equatorial conformer is more stable by 1.70 kcal/mol.

Since there are two gauche interactions, and the strain energy is 1.70 kcal/mol,
it’s easy to calculate the value of each interaction: 0.85 kcal/mol .
Ranking The Bulkiness Of Substituents On Cyclohexanes:
“A-Values”

“A-Values” For Substituted Cyclohexanes

“A-Values” are a numerical way of rating the bulkiness of substituents on a
cyclohexane ring. The “A-Value” represents the difference in energy (in kcal/mol)
between the cyclohexane conformation bearing the group in the equatorial position
(more favored) and the cyclohexane conformation bearing the group in the axial
position. The greater the “A-value” the higher the energetic preference for the
equatorial position, and the more “bulky” the group is considered.
Ethyl (1.75 kcal/mol)
An ethyl group is one carbon larger than a methyl group. Naively, we might
think that since it’s twice as long, it has twice as much steric hindrance, and the
energy difference would be twice as big. However, the difference in energy is
only 1.75 kcal/mol (compare to methyl at 1.70 kcal/mol). This is because the
only significant diaxial interactions are with the CH 2 group. The ethyl group can
rotate such that the CH3 points away from the ring, where it does not lead to any
significant increase in strain.
Hydroxyl (OH) (0.87 kcal/mol)
Given that oxygen has a larger atomic number than carbon, it’s not unreasonable to
think that the OH group might be “bulkier” than carbon. When you think about the
source of strain in CH3, however, you realize that it’s not necessarily the size of the
carbon atom itself but the hydrogens of CH3 interacting with the axial hydrogens on
the ring that lead to strain. Oxygen, having only one hydrogen, can always rotate
such that the H is pointing away from the cyclohexane, thereby leading to very little
in the way of diaxial interactions with the ring.
Br (0.43 kcal/mol)
Along similar lines one could be forgiven for thinking that Br, being such a heavy and large
atom, might exert a large destabilizing influence when in the axial position. However, the
difference is only 0.43 kcal/mol, less than that for OH. Why might this be? The answer here
is bond length. The average C-Br bond is about 193 picometers in length (1.93 Angstroms) –
compare this to 1.50 for the bond between C and CH 3 in cyclohexane. The Br, being farther
away, will thus have less interaction with the axial hydrogens. [Note – this A value of 0.43 is
the average of two experimentally determined values [0.38 and 0.48]. ]
Interestingly, despite their great difference in size, the A values for Cl, Br, and I are all
roughly similar (about 0.43 or so). This is because the increased size is balanced by the
increased bond length – the halogens might be increasing in size along Cl <Br < I – but they
are also getting farther away.
 Isopropyl [-CH(CH3)2] (2.15 kcal/mol)
In contrast to ethyl, which has a secondary carbon
attached to the ring, the isopropyl group represents a
tertiary carbon attached to the cyclohexane. There is
a relatively small but significant increase in strain to
2.15 kcal/mol . This is because the isopropyl group
can still adopt a conformation where the C-H bond
lies over the cyclohexane ring, which does not bring it
into significant contact with the axial C-H bonds.
tert-butyl [-C(CH3)3] (4.9 kcal/mol)
This is the biggie. Look at the huge difference in energy between t-butyl
(4.9 kcal/mol) and isopropyl (2.15 kcal/mol). What might account for
that extra 2.7 kcal/mol in strain energy.

It helps to look at a figure.

Notice how there’s no way to rotate the t-butyl group such that the methyl
group is NOT pointing over the ring. A diaxial interaction between one of the
methyl groups and an axial C-H is unavoidable. Axial t-butyl groups are
strongly disfavoured.
What is the consequence of that value of 4.9 kcal/mol ? If we calculate the
equilibrium constant K , it gives us a ratio of about 10,000 : 1

In other words, the concentration of axial t-butyl is 1/10,000 of that of equatorial t-

butyl.

This value is so small that we often think of the t-butyl group as “locking” the
cyclohexane ring in a position where the t-butyl is equatorial.

As we’ll see, this will have very important consequences for future reactions you’ll
learn such as substitution and elimination, which can be sensitive to stereochemistry.
It’s nice to have some shorthand. For a mono-substituted cyclohexane, the energy
difference between axial and equatorial conformers with a given substituent is
known as its A-value.
For example, the A value of methyl is 1.70 , ethyl is 1.75, OH is 0.87, Br is 0.43,
i-Pr is 2.15, and t-Bu is 4.9 .
A-values are useful because they are additive. We can use them to figure out the
energy differences between di- and trisubstituted cyclohexanes.
 Conformations of Monosubstituted Cyclohexanes

Even though cyclohexane rings flip rapidly between chair conformations at

room temperature, the two conformations of a monosubstituted cyclohexane
aren’t equally stable. In methylcyclohexane, for instance, the equatorial
conformation is more stable than the axial conformation by 7.6 kJ/mol (1.8
kcal/mol). The same is true of other monosubstituted cyclohexanes: a
substituent is almost always more stable in an equatorial position than in an
axial position.
You might recall from your general chemistry course that it’s possible to
calculate the percentages of two isomers at equilibrium using the equation
ΔE = –RT ln K, where ΔE is the energy difference between isomers, R is
the gas constant [8.315 J/(K·mol)], T is the Kelvin temperature, and K is
the equilibrium constant between isomers. For example, an energy
difference of 7.6 kJ/mol means that about 95% of methylcyclohexane
molecules have an equatorial methyl group at any given instant while only
5% have an axial methyl group. Figure plots the relationship between
energy and isomer percentages.
 The energy difference between axial and equatorial conformations is
due to steric strain caused by 1,3-diaxial interactions. The axial methyl
group on C1 is too close to the axial hydrogens three carbons away on
C3 and C5, resulting in 7.6 kJ/mol of steric strain

Interconversion of axial and equatorial methylcyclohexane,

represented in several formats. The equatorial conformation is more
stable than the axial conformation by 7.6 kJ/mol.
The 1,3-diaxial steric strain in substituted methylcyclohexane is already
familiar.
Gauche butane is less stable than anti butane by 3.8 kJ/mol (0.9 kcal/mol)
because of steric interference between hydrogen atoms on the two methyl
groups. Comparing a four-carbon fragment of axial methylcyclohexane
with gauche butane shows that the steric interaction is the same in both
(Figure 4.15). Because axial methylcyclohexane has two such
interactions, it has 2 × 3.8 = 7.6 kJ/mol of steric strain. Equatorial
methylcyclohexane has no such interactions and is therefore more stable.
The origin of 1,3-diaxial interactions in
methylcyclohexane. The steric strain between
an axial methyl group and an axial hydrogen
atom three carbons away is identical to the
steric strain in gauche butane. (To display
clearly the diaxial interactions in
methylcyclohexane, two of the equatorial
hydrogens are not shown.)
The exact amount of 1,3-diaxial steric strain in a given substituted
cyclohexane depends on the nature and size of the substituent.
Not surprisingly, the amount of steric strain increases through the series H3C− <
CH3CH2− < (CH3)2CH–<< (CH3)3C−, paralleling the increasing size of the alkyl
groups. Note that the values given in Table 4.1 refer to 1,3-diaxial interactions of
the substituent with a single hydrogen atom. These values must be doubled to
arrive at the amount of strain in a monosubstituted cyclohexane
Monosubstituted cyclohexanes are always more stable with their
substituent in an equatorial position, but the situation with disubstituted
cyclohexanes is more complex because the steric effects of both
substituents must be taken into account. All steric interactions for both
possible chair conformations must be analyzed before deciding which
conformation is favored.

Let’s look at 1,2-dimethylcyclohexane as an example. There

are two isomers, cis-1,2-dimethylcyclohexane and trans-1,2-
dimethylcyclohexane, which must be considered separately. In
the cis isomer, both methyl groups are on the same face of the
ring and the compound can exist in either of the two chair
conformations shown in Figure .(It may be easier for you to
see whether a compound is cis- or trans-disubstituted by first
drawing the ring as a flat representation and then converting it
to a chair conformation.)
Conformations of cis-1,2-dimethylcyclohexane. The two
chair conformations are equal in energy because each has
one axial methyl group and one equatorial methyl group.
Both chair conformations of cis-1,2-dimethylcyclohexane have one axial
methyl group and one equatorial methyl group. The top conformation in
Figure 4.16 has an axial methyl group at C2, which has 1,3-diaxial
interactions with hydrogens on C4 and C6. The ring-flipped conformation
has an axial methyl group at C1, which has 1,3-diaxial interactions with
hydrogens on C3 and C5. In addition, both conformations have gauche
butane interactions between the two methyl groups. The two
conformations are equal in energy, with a total steric strain of 3 × 3.8
kJ/mol = 11.4 kJ/mol (2.7 kcal/mol).
In trans-1,2-dimethylcyclohexane, the two methyl groups are on opposite sides of the
ring and the compound can exist in either of the two chair conformations shown in
Figure 4.17. The situation here is quite different from that of the cis isomer. The top
conformation in Figure 4.17 has both methyl groups equatorial with only a gauche
butane interaction between them (3.8 kJ/mol) but no 1,3-diaxial interactions. The ring-
flipped conformation, however, has both methyl groups axial. The axial methyl group
at C1 interacts with axial hydrogens at C3 and C5, and the axial methyl group at C2
interacts with axial hydrogens at C4 and C6. These four 1,3-diaxial interactions produce
a steric strain of 4 × 3.8 kJ/mol = 15.2 kJ/mol and make the diaxial conformation 15.2
− 3.8 = 11.4 kJ/mol less favorable than the diequatorial conformation. We therefore
predict that trans-1,2-dimethylcyclohexane will exist almost exclusively in the
diequatorial conformation.
Conformations of trans-1,2-
dimethylcyclohexane. The conformation with
both methyl groups equatorial (top) is favored
by 11.4 kJ/mol (2.7 kcal/mol) over the
conformation with both methyl groups axial
(bottom).
The same kind of conformational analysis just carried out for cis- and
trans-1,2-dimethylcyclohexane can be done for any substituted
cyclohexane, such as cis-1-tert-butyl-4-chlorocyclohexane (see Worked
Example 4.3). As you might imagine, though, the situation becomes
more complex as the number of substituents increases. For instance,
compare glucose with mannose, a carbohydrate present in seaweed.
Which do you think is more strained? In glucose, all substituents on
the six-membered ring are equatorial, while in mannose, one of the
−OH groups is axial, making it more strained.
A summary of the various axial and equatorial relationships among
substituent groups in the different possible cis and trans substitution
patterns for disubstituted cyclohexanes is given
 Conformation analysis of 2-bromocyclohexanone

The conformational analysis of 2-halocyclohexanones has

been investigated since the 1950s, when Allinger and
Allinger1 noted the difficulty in identifying the carbonyl
bands for the 2-bromocyclohexanone isomers
• The conformational behavior of 2-bromocyclohexanone
can be interpreted as follows.
• In the vapor phase and in non-polar solvents, three factors
may contribute to a preference for the axial conformation

• A steric effect between the lone pairs of the oxygen and

the - substituent and a repulsive dipole–dipole interaction
(both in the equatorial conformer) and an interaction
between the nBr and p*CO orbitals.
• In polar solvents, the second factor will be decreased and
the equatorial conformer becomes more stable and has the
larger population.
• In polar solvents, the second factor will be
decreased and the equatorial conformer
becomes more stable and has the larger
population.
• However, the predominance of the equatorial
conformer is also favored by the occurrence of
an attractive nO –nBr interaction through the
bonds via the σ*CC orbital and by the charge
stabilization for the equatorial conformer in
polar solvents, owing to the higher acidity of
the axial -hydrogen, in comparison with the
corresponding equatorial -hydrogen.
• Moreover, the axial conformation presents 1,3-
diaxial repulsion between bromine atom and
the syn axial hydrogens.
Overall stabilization effects in axial-X conformation of
2‑halocyclohexanones clearly increases in the order of
F < Cl < Br < I.
However, the ‘gauche effect’ participates, which is
stabilizing the equatorial conformation in largest
extent for F, also for Cl, has almost zero effect for Br,
and has a negative effect for I.