Last modified 9/7/12
Chem 223 Lab
Borohydride Reduction of Camphor
Ketones are conveniently reduced to secondary alcohols by metal hydride reducing agents such
as sodium borohydride or lithium aluminum hydride. In this experiment you will reduce camphor
with sodium borohydride. The reaction produces two products, borneol and isoborneol. If the
borohydride approaches camphor from the ‘underneath’ side (endo attack), then isoborneol will
result, but if attack is from the top (exo attack), then borneol is produced.
CH3
CH3
CH3
Borneol
H+
BH4-
H3C
CH3
H3C
CH3
O
BH4-
H
OH
CH3
H+
Isoborneol
OH
H3C
H
The reaction product will be purified by sublimation and the composition determined by nuclear
magnetic resonance and the results will be compared to predictions made by molecular
modeling.
Part A: Building Borneol and Isoborneol with Spartan: bring Thinkpad and power supply
to lab. Results used to answer post-lab questions.
1. Open the program Student Spartan. YOU MUST HAVE
DOWNLOADED THIS BEFORE PRE-LAB LECTURE.
2. Open a new file using the dropdown menu File→New.
3. On the bottom right-hand side of the screen beside the word “Rings”
select cyclohexane from the dropdown menu. Click in the middle of
the screen. A chair conformation of cyclohexane should appear.
Click and drag on any gray atom to rotate the molecule.
4. Now click on the sp3 hybridized carbon in the table and add an sp3 C
to one of the axial positions on cyclohexane. The methyl group is
bonded to C-1 and will itself become C-7 in the bicyclic ring system.
5. Make a bond between an open valence on the methyl group and the
equatorial valence directly across the ring (on C-4) using the ‘make
bond’ icon ( ). (Click on the icon and then on the two open
valences.) This should produce a distorted bicycloheptane system.
Upon clicking the minimize button ( ), you should be given a more
normal bicycloheptane.
axial methylcyclohexane
10
CH3
7
4
5
1
6
H3C
Sample bicycloheptane ring
9
H3C
3
2
8
isoborneol
6. Finish the molecule by adding three sp3
C’s and the O that will become the OH.
distorted
“normal”
OH
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(Add OH exo for isoborneol or endo for borneol.) Recall the Spartan will assume that any
remaining open valences are bonds to H.
7. Click
.
8. Click
and carefully check the structure you have built. If you need to alter the structure,
click
to get back into the builder.
9. Save the file as either borneol or isoborneol, depending on which one you built.
Finding the Lowest Energy Conformations of Borneol and Isoborneol:
10. You should have either borneol or isoborneol open. For clarity, close any other files.
11. Use the dropdown menu Setup  Calculations. Choose "Equilibrium Conformer". Click
submit.
12. Once the calculation is complete, use the dropdown menu Display→Output to view the
results. Scroll down the display window until you see “Lowest Energy Conformation.” Write
down the energy value, which is given in kJ/mole.
13. Run a new calculation to obtain the molecule’s heat of formation. Use the dropdown menu
Setup  Calculations. Choose "Equilibrium Geometry" with the “Semi-Empirical” PM3
model. Click submit.
14. Once the calculation is complete, use the dropdown menu Display→Output to view the
results. Scroll down the display window until you see “Heat of Formation.” Write down the
energy value, which is given in kJ/mole.
15. If you have not already done so, build the second reaction product. It is easy to convert
borneol to isoborneol (and vice versa). First, change the file name to the name of the
compound you will make. Then go to the builder ( ). Delete ( ) the oxygen. Choose the
divalent oxygen in the chart and then add the O to the other position (endo if it was exo or
exo if it was endo.) Minimize the energy ( ) and view the new structure ( ).
16. Repeat steps 10-14 for the other molecule.
To View and Capture the Lowest Energy Conformation Images:
17. Close all Spartan files.
18. Open the file containing the minimized E conformer of either borneol or isoborneol.
19. Use the dropdown menu Model  Tube to display the molecule in a less bulky format.
20. Position the molecule in the Spartan window EXACTLY as you wish it to appear in Word.
21. Under the dropdown menu File→Save Image As. Click OK and save the file on your laptop.
Insert this file as an image into your lab report so your TA can see your lowest energy
conformation of each molecule. Under Above the molecule, write its name, and below it give
its heat of formation in kJ/mol.
22. Repeat steps 17-21 for the other reaction product.
Part B: Reaction Procedure
Place 2 mL of methanol in a 10 mL rb flask, and add 0.5 g of camphor. Swirl until the camphor
dissolves, and then add 0.3 g of sodium borohydride. CAUTION. Do not add the borohydride
all at once; divide it into four or five portions and add over a period of about five minutes, with
swirling. Cool the flask in an ice bath, as necessary, to keep at room temperature. After the last
portion of borohydride has been added, heat to gently boiling for one minute on a hotplate.
Pour the hot reaction mixture into a 50 mL beaker that is about 2/3 full of crushed ice. Complete
the transfer by rinsing the reaction flask with 2 mL of methanol. Swirl the beaker occasionally,
and when the ice melts, collect the white solid by suction filtration and allow the material to air
dry for about 30 minutesa. You could hasten the drying by blotting the crystals with a dry paper
towel and gentle warming on a hotplate. Purify the material by sublimation. Transfer the
crystals to a dry100 mL beaker. Place the beaker directly on a hot plate and make a ‘tent’ of
Last modified 9/7/12
aluminum foil around the sides of the beaker and the base of the hotplate. In this manner, when
heat is applied, the sides, as well as the bottom, of the beaker will be heated. Atop the beaker
place a clean (on the outside!) 100 mL round-bottomed flask half-full of room-temperature water.
The bottom of this flask should make contact with the top of the beaker. Apply heat. You
should notice the appearance of product on the upper sides of the beaker and on the bottom of
the flaska. Periodically check the temperature of the water in the flask; if it warms to above 40o,
add crushed ice via a powder funnel such that the temperature drops below 30. Ideally, all the
material would sublime onto the flask. However, it is likely that some of your product will remain
on the side of the beaker. When no more white material remains in the bottom of the beaker
discontinue heating and scrape the product off the bottom of the flaskb,c. Add to this product any
crystals that you can scrape from the upper sides of the beaker. Determine your yield and turn
in the product in a labeled vial to the instructor. At the end of the lab a representative sample
will be taken to the NMR lab for analysis.
a
If the product is wet, water droplets will appear on the bottom of the round-bottomed flask. Do
not despair; simply blot the surface dry and continue.
b
If you have too much product for sublimation, it may be necessary to momentarily interrupt the
process to scrape sublimate off into a vial and then continue with the remainder.
c
Some inorganic boron-containing residue may remain in the bottom of the flask.
Product Analysis (ON YOUR OWN TIME WITH MNova)
View, integrate, and print the 1H NMRs of authentic samples of camphor, borneol and
isoborneol locatedon the lab website. Examine the spectra to find places where they differ.
Probably the best place to distinguish between borneol and isoborneol is between 3.4 and 4.2 ,
but you may find another that you like better. View the spectrum of the reaction product.
Determine the composition of the product (camphor, borneol, and isoborneol) by analysis of the
integrated spectrum. Report the composition of the product. Is there any unreacted camphor
present? Include printed copies of your processed NMRs with your lab report, as well as a
section called NMR analysis where you explain how you analyzed the product mixture.
Postlab Questions
1. Find the lowest energy conformer of both borneol and isoborneol and its energy. Include a
printout in your report that shows each lowest energy conformation and its energy in
kcal/mole.
a. Which compound is more stable, borneol or isoborneol?
b. Can you suggest the likely source of the strain that is present in the less stable
isomer? Hint: Use Spartan to look for crowding as evidenced by distorted bond
angles. You’ll need to measure bond angles with Spartan. With a structure open,
click
and then 3 atoms. Spartan will display the angle in the bottom right corner
of the screen. Be careful when selecting the atoms. The angle displayed is the
angle about the 2nd atom you choose, so choose them in order!
2. Is the lower energy product the major product of the reaction based on NMR data? Is the
reaction proceeding under thermodynamic or kinetic control?
H
CH3
3. If the borohydride reduction is performed on the compound shown to the
right, the exo vs. endo percents are almost exactly reversed as compared to
camphor. Suggest an explanation for this reversal in product
stereochemistry.
4. Give a method other than 1H NMR that could be used to look for unreacted
camphor in this experiment.
H3C
O