Download Expt 3. Molecular modeling of cycloalkanes

CHEM 350
Principles of Organic Chemistry I Lab
Prof. T. Nalli, WSU
Expt #3 - Molecular Modeling of Cycloalkanes
Relevant Reading – Smith, Chapter 4.11-4.13, 2.1-2.6, 3.1-3.2, 3.4-3.5, 3.9, 10.13. Pavia,
Expts 16b, 16c.
Overview
Cyclic structures present conformational complexities not present in acyclic molecules.
In this lab you will use models and Chem3D modeling software to explore the
conformations of some cyclic alkanes, especially cyclohexane and its mono- and disubstituted derivatives.
Definitions
Strain - Any factor that increases the potential energy of a molecule.
Torsional Strain - Strain associated with an eclipsed single bond.
Steric Strain - Strain due to two atoms being too close to each other in space. If the
distance between the atoms is less than the sum of the Van der Waal's radii of the atoms
then there is steric strain.
Angle Strain - Strain due to bond angles in a molecule not being able to attain ideal
values (i.e., the values predicted by VSEPR theory). Due to a combination of extra
electron pair repulsion (bonding electron pairs too close) and/or poor orbital overlap
resulting in weak, bent bonds.
Ring Strain - The strain associated with a cyclic structure. This could be due to one or
more of the three fundamental types of strain, torsional, steric, and angle.
PROCEDURES
Record all data, observations, and structural drawings directly in the lab notebook as
you do this experiment. Make all models both with the Molymod kit and on the
computer in Chem3D. Chem3D instructions are consistently given in italics throughout
this handout.
Conformations of Cyclohexane
1. The Chair
Construct a model of cyclohexane by joining six carbons in a ring and then adding two
hydrogens to each carbon. First try to make the six carbons all lie in one plane. Note
your observations carefully on this hypothetical planar form of cyclohexane. (Making a
planar model of cyclohexane using ChemOffice will be next to impossible so don’t try.)
By rotating some of the bonds you should be able to make your cyclohexane model look
like the figure below. The model should sit firmly on the desktop with three hydrogens
serving as legs. This model represents the chair conformation of cyclohexane.
H
H
H
H
H
H
H
H
H
H
H
H
In ChemOffice, the best way to build a complex structure is to first draw the molecule using
ChemDraw. Start up ChemDraw, click the cyclohexane tool (the hexagon) and then click in the
drawing area. Click the selection tool and either "lasso" the molecule or double click on it. A
dotted line box appears around the structure. (Or use Ctrl-A to “select all”). Copy (Ctrl-C or
<edit>, <copy>) the selection and then paste (Ctrl-V or <edit>, paste>) into the new model
window in Chem 3D. You should now have a model of cyclohexane in the chair conformation.
MM2-minimize the energy and record the total energy in your notebook.
Examine the cyclohexane chair conformation carefully and practice drawing it. (The
instructor will present some methods for helping you master this.) Next look for
“strain” in the molecule.
 Sight down each of the carbon-carbon bonds in the molecule. Are the
bonds staggered or eclipsed? Draw a Newman projection for one of the CC bonds. Simply use "CH2" for bonds that lead back into the ring. Does the
Newman projection you draw depend on which bond you pick?
 Do any of the bonds in your model appear to be bent? You can check the
bond angles in Chem3D by clicking <analyze> <show measurements> <show
bond angles>.
 Do any of the atoms in the model appear to be particularly close together?
(You can view a space-filling model in Chem3Dby selecting <View> <Settings>
and selecting “Space Filling”under Model Type.)
Use your observations to conclude as to what types of strain (see definitions)
cyclohexane possesses, if any.
Try to describe the symmetry elements present in the cyclohexane chair. Also note that
three of the hydrogens point straight up and three point straight down. These
hydrogens are said to be in axial positions. (Imagine the ring as a wheel. These
hydrogens point out in the same direction as the axis of the wheel would.) The other six
hydrogens radiate outward along the perimeter of the ring. These hydrogens are in
equatorial positions. If you numbered the six carbons of the ring, which carbons would
have axial hydrogens that are on the same side of the ring. Once again, draw the chair
conformation of cyclohexane and this time label all of the hydrogens as equatorial (eq)
or axial (ax).
2. The Boat
By grasping one of the carbons with an axial hydrogen pointing down and forcing it to
point up (bond rotations are required), you should be able to get your model to look
like a boat. (See figure below.) This conformation of cyclohexane is referred to as the
boat.
boat
Arriving at the boat conformation of cyclohexane using this software is difficult so use the one in
the file that the instructor emails you. Click <File>, <Open>, and double click on the boat.C3D
file in the folder which contains your email attachments.
Look carefully for strain in the boat conformation using the same process as described
above for the chair (the bulleted list on the previous page). Record all observations and
data in the notebook. Depict any strain you find with a structural drawing, e.g., a
Newman projection for torsional strain. Also make sure to compute the relative energy
of this conformation by clicking <MM2> <Minimize Energy> <Run>.
Other conformations of cyclohexane include the half chair and the twist conformations:
half chair
twist
3. The Twist
The twist can be arrived at by starting with the boat, grasping the carbons that would
represent the bow and stern of the boat, and pulling them slightly away from each other
and in opposite directions with respect to the plane of symmetry which they lie in. (See
figure below).
In Chem3D, take your boat and run an energy minimization (<MM2>, <Minimize Energy>)
setting the Minimum RMS Gradient to 0.001. Make sure to record the resulting energy in your
notebook. The model you now have is the twist.
Look carefully for strain in the twist conformation using the same process as before.
Record all observations and data in the notebook. Depict any strain you find with a
structural drawing, e.g., a Newman projection for torsional strain.
4. The Half Chair
The half chair can be arrived at by stopping halfway on the way from the chair to the
boat. At this point, five of the carbons lie in the same plane. Make a model of the halfchair.
Arriving at the half chair conformation of cyclohexane using this software is difficult so use the
one in the file that the instructor emails you. Click <File>, <Open>, and double click on the half
chair.C3D file in the folder which contains your email attachments.
Look carefully for strain in the half chair conformation using the same process as before.
Record all observations and data in the notebook. Depict any strain you find with a
structural drawing, e.g., a Newman projection for torsional strain.
Determine the energy of the half chair by selecting <MM2> <Compute Properties> and
selecting Steric Energy Summary and <Run>. Now run an energy minimization (<MM2>,
<Minimize Energy> <Run>). What conformation do you end up with?
Conformations of Monosubstituted Cyclohexanes
For the remainder of the lab consider chair conformations only.
Remove an equatorial hydrogen from the cyclohexane model and add a CH3 group in
its place to form methylcyclohexane. In Chem3D start with the cyclohexane chair, and use
the atom tool (The “A”) to select one of the equatorial hydrogens and then type "CH3" and hit
enter. Run an energy minimization and record the steric energy.
Carefully draw the structure represented by the model.
Now grasp and invert any carbon (C-1) to form a boat conformation. Then take C-4 and
invert it to remake a chair conformation. This process inverts the chair conformation
and is called chair flipping (See figure below).
Flipping the chair to the boat and then flipping the boat to the other chair is impossible using this
software. The instructor will demonstrate these ring flips using a physical model and a computer
animation.
Carefully draw the structure represented by this model. Generalize as to what chair
flipping does to substituents in terms of their equatorial/axial status.
Notice that chair flipping is accomplished easily by single bond rotations and so
happens easily at room temperature (like any conformational interconversion).
Observe both chair conformations of methylcyclohexane looking for strain. You’re your
observations using structural diagrams as appropriate to show any strain present.
Which chair conformation of methylcyclohexane is more stable? Why?
Conformations of Disubstituted Cyclohexanes
1,2-Dimethylcyclohexane (diequatorial)
Starting with the above model in the chair conformation with the methyl group
equatorial, replace the equatorial hydrogen on an adjacent ring carbon (C-2) with a
second methyl group. Force the ring to be planar for a moment and observe whether
the methyl groups are on the same side of the ring, “cis”, or on opposite sides, “trans”.
Look carefully for strain interactions in this model and note your observations.
In Chem3D start with the equatorial methylcyclohexane, and use the atom tool (The “A”) to
select the equatorial hydrogen on one of the adjacent ring carbons and then type "CH3" and hit
enter. Run an energy minimization and record the steric energy.
Flip the ring to its other chair conformation. Observe the positions of the methyl groups
now. Did the methyl groups’ stereochemical relationship (i.e., cis or trans) change?
Again, look carefully for strain interactions in this model and note your observations.
Which of the two chairs do you think is more stable? Explain.
Make a model of the flipped chair in Chem3D and run an energy minimization and record the
steric energy. Check your answer to the previous question against the molecular
mechanics results (the steric energies) for the two chair forms. If it does not agree then
revisit the question and figure out where your prediction went wrong.
1,2-Dimethylcyclohexane (equatorial - axial)
Now make a model of 1,2-dimethylcyclohexane with one of the methyl groups in an
equatorial position and the other in an axial position. Force the ring to be planar for a
moment and answer the next question and decide whether the methyl groups are cis or
trans. Look for strain and note your observations.
As before build this model in Chem3D and compute the steric energy through an energy
minimization.
Flip the ring to its other chair conformation. Did the methyl groups’ stereochemical
relationship (i.e., cis or trans) change? Again, look for strain and note your observations.
Which of the two chairs do you think is more stable? Explain. It is unnecessary to build
this model in Chem3D. Why?
1,3- and 1,4-Dimethylcyclohexane
Now make a model of cis-1,3-dimethylcyclohexane. Examine ring flipping and draw
both chair conformations. Observe each carefully for strain interactions. Which chair
should be more stable? Why? Use Chem3D to test your prediction. (Build models of
both conformations, run energy minimizations on each, and compare the resulting
steric energies.)
Repeat the previous paragraph for trans-1,3-dimethylcyclohexane, cis-1,4dimethylcyclohexane, and trans-1,4-dimethylcyclohexane.
Conformations of some other Substituted Cyclohexane Rings
There are two stereoisomers of 1,3,5-trimethylcyclohexane, cis-trans-trans and all-cis.
CH3
H3C
CH3
CH3
all-cis
H3C
CH3
cis-trans-trans
Which isomer is more stable? (Make models to make sure!). Draw the molecule in its
most stable conformation.
Make a model of cis-1-bromo-4-tert-butylcyclohexane. In the most stable conformation
of this compound what type of position does the bromine find itself in? Why? Draw the
molecule in its most stable conformation.
Compared to the difference in stability between alternative chair conformations of the
other compounds examined in this experiment, the difference in stability between the
two chair conformations of cis-1-bromo-4-tert-butylcyclohexane is quite large. Explain
why.
Conformations of some other Cycloalkanes
Make a model of cyclopropane. Are there multiple conformations of the cyclopropane
ring possible like there are with cyclohexane? Identify all strain interactions present in
cyclohexane. Is this a stable molecule?
Make a model of cyclopentane. Can you find a conformation of this ring that is strainfree? Identify the type of strain present in all possible conformations of this molecule.
Make a model of cycloheptane. There are many conformers possible for this molecule.
Use Chem3D to find two conformers (energy minima!) and draw these in your
notebook. Identify the types of strain potentially present in any given cycloheptane
conformation.
Post-Lab Questions
1. Draw an energy diagram showing a cyclohexane chair flip. Go from a chair to the half
chair to the twist and then back again to the half chair and the other chair. The half chair
and boat conformations are not properly referred to as “conformers”. Why not?
2. Which isomer of dimethylcyclohexane is the most stable? Explain.
3. Indicate the preferred position (axial or equatorial) of the bromo substituent in each
of the following.
a. trans-1-bromo-4-tert-butylcyclohexane
b. cis-1-bromo-3-tert-butylcyclohexane
c. trans-1-bromo-3-tert-butylcyclohexane
d. cis-1-bromo-2-tert-butylcyclohexane
e. trans-1-bromo-2-tert-butylcyclohexane
f. 1-bromo-1-tert-butylcyclohexane