Note

pubs.acs.org/joc

Regioselectivity of Organolithium Addition to an

Enone
Austin C. Cao, Meredith McDowell, Paul S. Engel

Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005

April 23, 2016

white aerosol
and condensation
on the sides
ABSTRACT: Enones allow for both 1,2-addition
and 1,4-addition
of an incoming
nucleophile. In this
of the flask. Rapid cooling with the ice
water bath helped collect more of the
desired product. The yield was very high on
this second step, which can be attributed

Carboxylic acids can be converted to

esters through a variety of methods,
including
the
classic
Fischer
esterification 1
and
Steglich
esterification. In this experiment, we
demonstrate an alternative method,
where
the
carboxylic
acid
is
converted to its acid chloride form2
before esterification is carried out.
There are a few benefits to this
approach: the esterification takes less
time, the product requires a less
involved purification, and the reaction
is not in equilibrium, so 3the yield of
ester should be improved.
Thionyl chloride was used to convert
pivalic acid to pivaloyl chloride. After
reflux, a clear, transparent liquid with
a white aerosol above was observed.
The presence of acid chloride, the
desired intermediate, was confirmed
by
TLC
and
IR
spectroscopy.
Specifically, we observed that the OH
peak around 3500 cm-1 disappeared
while the C=O peak around 1750 cm -1
remained. During vacuum distillation,
a significant quantity of product was
lost when too much heat was applied
to the apparatus. In part, this error
occurred because the thermometer
only monitored the temperature of the
vapor and not of the solution itself.
Thus, the poor yield on this first step
can be explained by the loss of
product during distillation.
During the second step, isobutyl
alcohol was added, quickly produced a

to the irreversible reaction that occurs

between the acid chloride and the alcohol.
IR spectroscopy confirmed the presence of
isobutyl pivalate. The C-O stretch at
1200.75 cm-1 and the C=O stretch at
1732.38 cm-1 are characteristic of an ester.
While not labelled as a stretch, the small
curve around 3500 cm-1 suggests that some
unreacted alcohol may still be left in
solution. Furthermore, NMR spectroscopy
showed the presence of isobutyl pivalate,
indicating the success of this method of
esterification.

Figure 1. Mechanism for acid

chloride synthesis and esterification
of pivalic acid and isobutyl alcohol.

The Journal of Organic

Chemistry

Note

(92.5% yield) and a portion was

submitted to the
TAs for NMR
spectroscopy. 1H NMR (CDCl3):
3.84 (d, 2H), 1.94 (m, 1H),
1.23 (s, 6H), 1.20 (s, 9H), 0.93
(d, 9H).

EXPERIMENTAL
SECTION
The apparatus was set up
using a 500 mL 3-neck
round bottom flask and a
condenser.
A
thermometer
and
a
dropping
funnel
were
placed in the other two
necks, and an HCL trap
was attached to the top of
the condenser. A heating
blanket
was
placed
between the apparatus
and a heating plate, and a
magnetic stirred rod was
placed in the flask. Pivalic
acid (12 mL) was added to
the flask and heated up to
70 C. Thionyl chloride (24
mL) was placed in the
attached dropping funnel
and slowly added over 30
min. The solution was
refluxed for 90 min and
monitored
with
TLC.
Excess thionyl chloride was
removed
with
vacuum
distillation while heating at
90
C.
Product
was
collected (4.3% yield). To
carry out the esterification,
the same apparatus setup
was used the following
week. 0.56 mL of the
previously
obtained
product was added to the
flask and heated to 105 C.
After
reaching
reflux,
isopropyl alcohol (0.42 mL)
was drop-added by syringe
over 15 min. The flask was
then removed from the
apparatus and immediately
cooled in an ice water bath.
The product was then
collected and extracted
using water (2 mL) in a
separation funnel. Sodium
sulfate was used to dry any
remaining
water.
The
product
was
collected

The synthesis was scaled to

the volumes listed above,
which
differs
from
the
literature that informed this
experiment. Furthermore, the
apparatus was modified, as
detailed above, to utilize
available glassware.
ACKNOWLEDGMENTS
This project was done through
CHEM 365 Organic Chemistry
Lab with instruction from Paul
S. Engel. Special thanks to
Meredith McDowell, Marek
Buchman, and Tania Lopez for
their guidance.
AUTHOR CONTACT
Austin C. Cao
(acao@rice.edu)
Meredith McDowell
(mwm2@rice.edu)
Paul S. Engel
(engel@rice.edu)
REFERENCES
1

Engel, P.S. CHEM 365 Organic Chemistry

Lab Manual, Spring, 2016.
2
Knig, B. Reaction of cinnamic acid with
thionyl chloride to cinnamoyl chloride.
Universitt Regensburg. 2013.
3
Wells, J.D. Preparation of Isobutyl
Propionate. Townson University.