Macquarie University
CHEM3601 - Advanced Synthesis
FEI LIU
EXPERIMENT 4
Wagner-Meerwein Rearrangements
Pre-lab:
The commercial conversion of camphene (3,3-dimethylbicyclo [2.2.1] heptane) to isobornyl
acetate (1,7,7-trimethylbicyclo[2.2.1]heptan-exo-2-ol acetate is a classic example of a
Wagner-Meerwein rearrangement. This reaction was first discovered in the bicyclic terpenes
so we have chosen such a system to demonstrate the reaction even though it occurs in many
other systems. Rearrangement is common in neopentyl-(Me3CCH2-) neophyl-(PhCMe2CH2-)
systems where normal nucleophilic substitution is difficult due to steric hindrance; for
example:
CH 3
OH
H 2O/H+ /Δ
CH 3 OTs
CH 3 CH 3
The product formed by addition of acetic acid to camphene is a secondary acetate rather than
the expected tertiary acetate. The explanation for this seemingly unlikely reaction is that the
two cations (rearranged and unrearranged) are in resonance in what is called a “non-classical”
carbocation. The question now becomes; why does the acetate attack the secondary centre
instead of the tertiary?
H 2O/H+ /Δ
HOAc
AcO
H
As part of the prelab for this experiment, look up the mechanism of this rearrangement and
make a molecular model of the carbocation and show yourself how the migration of only
one bond can cause the movement of so many groups. In addition, prepare a flow-diagram
outlining the steps in the labwork and showing the fate of every reagent and solvent. Lastly,
obtain an SDS for every reagent and complete a risk assessment before coming to lab.
Lab work:
In a 50 mL Erlenmeyer flask dissolve 3 g of camphene in 7 mL of glacial acetic acid. Add
0.4 mL (8 drops) of 30% sulfuric acid and warm the flask on the steam bath with frequent
swirling for 15-20 minutes. Add 4 mL of water, mix well, and allow to cool. Transfer the
mixture to a large test tube and rinse the flask with a little water to remove the last traces of
product. Use a Pasteur pipette to withdraw most of the lower aqueous layer. Wash the crude
product first with water, then saturated sodium bicarbonate and finally water. Dry the product
with anhydrous calcium chloride and transfer the clear liquid into a 10 mL round-bottom flask
from a semi-micro glassware kit using a Pasteur pipette, leaving the CaCl2.xH2O behind.
Attach a Hickman still head, thermometer and condenser, add a couple of boiling chips and
distil the product. Transfer the distillate to a tared sample vial. Collect the product and record
the exact boiling point and yield. Label your product and store.
Obtain an infrared spectrum of your product and compare it to that of the starting material.
Post-lab:
Prepare a succinct report following the instructions provided in the lab manual.
Show your working for the theoretical and experimental yields. In addition, discuss the IR
spectra you recorded and answer all the following questions.
1.
What is the mechanism for the reaction of camphene to isoborneol acetate (show all
details and intermediates and transition states)?
2.
Explain why the exo-isomer only is produced from this reaction even though this is
obviously the most hindered face. [Hint: look at the “non-classical” carbocation
intermediate].
3.
Explain, using mechanisms, why dehydration of isoborneol gives camphene.
4.
Draw the structure of 1,6,6-trimethylbicyclo[3.1.1]heptan-2-ol acetate. Why is this
product not formed from camphene + acetic acid?