GREEN OXIDATION OF BORNEOL TO CAMPHOR
WITH OXONE®
Background: Terpenes and Terpenoids
Terpenes are a class of hydrocarbon natural products that can formally be described as being
constructed from 5-carbon isoprene units. Terpenoids are similar, but can contain other nonhydrocarbon functional groups such as hydroxyls and carbonyls. The isoprene unit is one of the
common “building blocks” used to construct biological molecules. Nature doesn’t use the
isoprene molecule itself, but rather the structurally-related compounds isopentenyl
pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP).
OPP
isoprene
DMAPP
OPP =
OPP
IPP
O
O
O P O P O
O
O
From these simple building blocks, an amazing number and variety of terpene and terpenoid
products can be formed. Scheme 1 on the next page outlines the biosynthesis of borneol and
camphor from DMAPP and IPP.
Camphor has the distinction of being one of the first natural terpene products isolated from
nature with a rich and colorful history. It can be found in the camphor tree (cinnamomum
camphora), an evergreen tree found in Asia, and from many other plant sources. Camphor can
be synthetically produced from the oil of turpentine. Humans have found a wide range of uses
for camphor including medicinal applications (antimicrobial, anesthetic, cough suppressant),
plasticizer, embalming fluid, pyrotechnics, moth repellent, and preservative in pharmaceuticals
and cosmetics. See if you can find camphor on the label of any of your products at home.
-H+
-PPO
OPP
DMAPP
OPP
OPP
H
IPP
OPP
OPP
linalool synthase
linalool pyrophosphate
GPP
H 2O
-H+
[O]
OH
borneol
O
camphor
Scheme 1: Biosynthesis of Borneol and Camphor
The objective of this experiment is to oxidize (1S)-borneol to (1S)-camphor. This reaction has
practical utility, because the (1S)-enantiomer of borneol is much cheaper than the (1R)- ($0.97/g
vs. $95/g), but the (1S)-enantiomer of camphor is much more expensive than the (1R)- ($17/g vs.
$0.36/g). Therefore, if the oxidation can be done cheaply and in high yield, it can provide a
cheaper source of (1S)-camphor.
The Reaction:
Sodium hypochlorite (NaClO; household bleach) is a relatively cheap and environmentallyfriendly oxidizing agent capable of converting alcohols to ketones. In the presence of acid,
hypochlorous acid is presumably formed, which could oxidize the alcohol via the following
mechanism:
However, household bleach can vary in concentration, diminishing over time. Also, its
noxious vapors are an inhalation hazard. In this experiment, hypochlorite will be generated in
situ by oxidizing chloride (from NaCl) with Oxone®. This reagent, a product of DuPont, is a very
cheap, easy to handle, solid oxidant. Oxone® is a “triple salt” (2KHSO5.KHSO4.K2SO4)
containing potassium peroxymonosulfate (KHSO5) as the active oxidizing agent. In this
experiment, it us used to oxidize chloride to hypochlorite:
KHSO5 + Cl- + H+ à KHSO4 + HOCl
Because chloride is then regenerated when the alcohol reacts with hypochlorous acid, only a
catalytic amount of chloride is needed for the reaction.
Procedure3
Oxone® is a strong oxidant; do not inhale the dust. The aqueous components of an organic
Oxone® reaction are oxidizing and acidic and should be quenched with sodium bisulfite and then
neutralized with sodium bicarbonate before disposal.
NOTE: carefully measure the amounts of solvent using a pipette. The rate-determining step of
the reaction is second order, so the rate dramatically decreases with an increase in the solvent
volumes.
Your goal by the end of Day 1 is to have your crude product drying in a dessicator. On Day 2
you will purify your product by sublimation.
Clamp a 50-mL round bottom flask to a ring stand and position a magnetic stirrer beneath it.
Place a medium stir bar in the flask and add 1.0 g (6.5 mmol) of (1S)-borneol. Add 4 mL ethyl
acetate and begin stirring to dissolve the borneol. Add 2.4 g (3.9 mmol) of Oxone® (which
corresponds to 7.8 mmol of KHSO5) to the flask with continued stirring. Then add 0.08 g (1.4
mmol) NaCl, followed by 1.5 mL of deionized water. Allow the reaction to stir at room
temperature for 50 minutes. Then add an additional 0.03 g (0.5 mmol) NaCl. Continue to stir
for 10 more minutes. Note any changes in color or temperature during the entire procedure.
By the end of this time the oxidation should be complete and excess oxidant can be destroyed.
Add 15 mL of deionized water to the reaction and continue stirring to dissolve most of the salts.
Slowly add a spatula tip of solid sodium bisulfite to reduce the oxidants that remain. Test the
aqueous layer (not organic) by dipping a glass rod into it and then touching a piece of starchiodide paper. A blue-black color (positive test) indicates the presence of excess oxidant; add
small amounts of sodium bisulfite if the aqueous layer tests positive, until a negative test is
achieved (no color change).
Workup
Carefully transfer contents to a separatory funnel. Add 1 to 2 mL of ethyl acetate to the reaction
flask, swirl, and add this wash to the separatory funnel as well. Shake and invert the separatory
funnel and separate the layers by draining the aqueous layer from the bottom. Pour the organic
layer out of the top into a clean 50-mL Erlenmeyer flask. Extract the aqueous layer twice more,
with 5 mL of ethyl acetate each time. Return the combined organic phases to the separatory
funnel and wash three times with 5-mL portions of saturated aqueous sodium chloride solution
(brine). Pour the organic phase into a clean Erlenmeyer flask and dry over anhydrous sodium
sulfate.
Filter the solution into a tared Erlenmeyer flask. In the hood, heat gently on a hot plate and flow
a light stream of air over the solution to remove the ethyl acetate solvent. Excessive heating or
air flow can lead to sublimation and product loss, so it is important to monitor the concentration
step carefully, especially near the end when the solid product begins to form. Record a crude
mass before drying.
Desiccation
First, break up any large chunks of your product and/or material adhered to the walls of the flask
to aid in desiccation. Label your flask with your name and “Camphor”. Cover the mouth of the
flask with a Kimwipe using a rubber band, and place it in a CaCl2-containing dessicator. Rest the
Erlenmeyer flask inside a small beaker to keep it upright.
Next laboratory period, record the mass again to determine if excess water and/or solvent was
removed. Set aside a small amount of crude product for IR and potentially NMR analysis.
Sublimation
Your TA will demonstrate how to set up a small-scale sublimation apparatus. Purify your crude
camphor by sublimation. Collect the sublimed material onto a tared watch glass and obtain the
mass. Save the material for your TA’s inspection.
IR Interpretation
Obtain IR spectra for your crude and final products. Qualitatively assess the extent of
conversion in your crude product. Is your IR spectrum of your sublimed product consistent with
what you would expect?
1H
NMR Interpretation
You will be provided with 1H NMR spectra for borneol, camphor, one student’s crude camphor
product, and one student’s sublimed camphor product. Determine the percent conversion of
borneol to camphor in the crude sample, and assess the quality of the crude and final product. It
is not necessary to identify the chemical shift, splitting patterns, or coupling constants for every
single proton of these compounds since the spectra are quite complex. However, by identifying
signals that are diagnostic for each compound, and by integrating these signals, you can arrive at
a ratio of product to starting material. Also look for any evidence of impurities such as ethyl
acetate.