Watching microwave-promoted chemistry: reaction monitoring using a digital camera interfaced with a scientific microwave apparatus

Article abstract of DOI:10.1016/j.tetlet.2007.10.097

By interfacing a digital camera with a scientific microwave unit it is possible to monitor macroscopic effects as reactions proceed, including color and viscosity changes, evolution of gases, metal-mediated couplings, and arcing.

Full text of DOI:10.1016/j.tetlet.2007.10.097

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 195–198
Watching microwave-promoted chemistry:
reaction monitoring using a digital camera
interfaced with a scientific microwave apparatus
a
a,
b
*
Matthew D. Bowman, Nicholas E. Leadbeater and T. Michael Barnard
a
Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269-3060, USA
b
CEM Corporation, 3100 Smith Farm Road, Matthews, NC 28106, USA
Received 17 September 2007; revised 16 October 2007; accepted 18 October 2007
Available online 24 October 2007
Abstract—By interfacing a digital camera with a scientific microwave unit it is possible to monitor macroscopic effects as reactions
proceed, including color and viscosity changes, evolution of gases, metal-mediated couplings, and arcing.
ꢀ
2007 Elsevier Ltd. All rights reserved.
The use of scientific microwave apparatus for prepara-
tive organic chemistry is becoming increasingly com-
mon. Microwave heating offers advantages such as
short reaction times and good yields of desired products.
There are two main categories of scientific microwave
apparatus. Monomode microwave units have been used
with great success for small-scale reactions using sealed
glass tubes up to a working volume of approximately
be useful, but would add an extra degree of safety. When
using domestic microwave ovens, it can be possible to
watch reactions using the naked eye. However, it is
not possible to monitor key parameters such as temper-
ature, pressure, and microwave power. Also, it is inher-
ently unsafe to perform chemistry in a domestic
microwave oven since they are not designed for prepara-
tive chemistry and are not built to withstand a vessel
failure. However, using scientific microwave apparatus
it is possible to monitor very closely a range of parame-
ters and they are safe to use for chemistry. However, the
design of a scientific monomode microwave is such that
the cavity is sealed and you cannot see your reaction
mixture. Here we show how, by interfacing a digital
camera with a monomode microwave apparatus, it is
possible to watch reactions as they take place and we
highlight the benefits this brings.
1
5
0 mL or open round-bottom flasks to a volume of up
to 125 mL. Multimode apparatus has been used for scal-
ing up reactions as well as performing chemistry in
multiple vessels. When performing chemistry using a
microwave unit, in particular a monomode apparatus,
it is not generally possible to monitor a reaction as it
proceeds. Some approaches have been developed,
including the use of Raman spectroscopy as a tool for
2
in situ monitoring of reactions. We have used this to
probe both organic and organometallic reactions and
found that the ones we have investigated reach comple-
tion in a matter of seconds. While Raman spectroscopy
is a useful tool, something that preparative chemists do
conventionally is watch their reactions as they proceed.
Macroscopic phenomena such as changes in color, vis-
cosity, or the dissolution or deposition of solids can be
indicative of product formation or, in some cases,
decomposition. Thus, when using microwave heating,
to be able to see a reaction as it runs would not only
To perform our experiments, a commercially available
monomode microwave apparatus was interfaced with a
3
4
,5
digital camera.
The microwave unit contained an
access port in the side of the cavity, through which a
1.3 megapixel camera could be interfaced. The face of
the lens was positioned outside the cavity wall. To be
able to watch reactions as they proceed it was clearly
necessary to illuminate the microwave cavity. This was
achieved by placing white light LEDs in the bottom of
the microwave cavity these providing enough light to
illuminate a vessel. The end of the camera lens was pro-
tected with a plastic cover in case of a vessel failure in
the microwave cavity. The camera was connected to a
*
Corresponding author. Tel.: +1 860 617 3518; fax: +1 860 486
981; e-mail: nicholas.leadbeater@uconn.edu
2
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.097

196
M. D. Bowman et al. / Tetrahedron Letters 49 (2008) 195–198
PC and controlled using computer software. Reactions
were performed in sealed 10 mL glass tubes and were
recorded digitally. The videos are cited in the text here
and either the full experiment or else excerpts can be
found in Supplementary data.
based ionic liquids where the excess of halide is difficult
to remove completely. This has prompted the use of
microwave-mediated approaches for the preparation of
ionic liquids and several reports have appeared in the
8
literature. For our study, we prepared a solution of
N-methylimidazole and 1-bromopropane in toluene.
Heating this to a target temperature of 160 ꢁC, using
an initial microwave power of 300 W, and monitoring
the reaction using the camera, the formation of 1-pro-
pyl-3-methylimidazolium bromide ([BMIM]Br) was
evident. The initially clear solution first becomes cloudy
and then, after about 45–50 s, the yellow ionic liquid
starts to separate out of solution. The reaction, per-
formed on a 10 mmol scale, is complete after 90 s micro-
wave heating [video 5].
As a starting point, we studied the effects of microwave
heating on a reaction vessel containing water. Compared
to using a hotplate to heat a reaction mixture, micro-
wave irradiation leads to heating on a molecular level.
Since the microwave energy is interacting with the mole-
cules at a very fast rate, the molecules do not have time
to relax and the heat generated can, for short times, be
much greater than the overall recorded temperature of
6
the bulk reaction mixture. In essence, there will be
instantaneous localized superheating. We wanted to
see if this localized superheating could be physically
seen. To do this, we placed 2 mL water in a 10 mL glass
tube, put a septum on the vessel and placed it into the
microwave cavity. We then programmed the apparatus
to heat the water to a target temperature of 150 ꢁC.
Looking at the video of the experiment [video 1], locali-
zed heating is clearly apparent upon microwave irradi-
ation. We found that this became more significant
once the bulk temperature of the water was above
Our next reaction for study was the hydrolysis of ethyl
benzoate in aqueous ethanol containing potassium
hydroxide. In this case we wanted to follow the reaction
9
colorimetrically. Using a 1:1 stoichiometric ratio of
ethyl benzoate to potassium hydroxide and by adding
phenolphthalein to the solution, we proposed that it
would be possible to watch for disappearance of the
purple coloration, indicating point when all the KOH
was consumed by the benzoic acid formed in the hydro-
lysis reaction (Scheme 2). Heating the reaction mixture
to a target temperature of 120 ꢁC, using an initial micro-
wave power of 200 W, and monitoring the reaction
using the camera, we find that the hydrolysis is complete
within 35–40 s of irradiation [video 6].
1
30 ꢁC. To be able to see the superheating more clearly,
we performed an analogous experiment using 6 M
sodium hydroxide into which we had placed a small
quantity of fluorescein [video 2]. Again superheating is
apparent upon microwave irradiation. It is important
to note that both of these experiments were performed
in the absence of stirring. With stirring, more homo-
geneous heating is observed.
The use of microwave irradiation in polymer chemistry
is an emerging field of research, which is attracting
attention not only because reactions can be greatly
accelerated but because polymers with novel properties
Polar solvents absorb microwaves effectively while non-
polar solvents do not. To see the effect of this on the
superheating we performed an experiment using two
immiscible solvents, dichloromethane and aqueous
sodium hydroxide (containing fluorescein for clarity).
Since the density of dichloromethane is greater than that
of water, the organic solvent sits below the aqueous.
Heating this using microwave irradiation, localized
superheating is clearly seen, but only in the more
polar, aqueous layer [video 3]. Repeating the experiment
but using toluene in place of dichloromethane puts the
organic layer above the aqueous layer and again
localized heating is seen to originate solely from the
more polar, aqueous layer [video 4].
1
0
can be prepared. We wanted to study a polymerization
reaction using our reaction monitoring apparatus. We
chose the free-radical polymerization of methyl acrylate
1
1
for our study. Using azobisisobutyronitrile (AIBN) as
an initiator we expected to be able to see the decompo-
sition of this to give 2-cyanoprop-2-yl radicals and nitro-
gen gas and then the rapid polymerization of the alkene
to give polymethylacrylate. Performing the reaction
solvent-free, heating to a target temperature of 80 ꢁC,
using an initial microwave power of 150 W, and moni-
toring the reaction using the camera, we find that the
AIBN initiates the polymerization after about 45 s of
irradiation, this corresponds to a bulk temperature of
7
5 ꢁC and then the process being complete within 80 s
We moved from our foundation experiments to moni-
toring reactions. We first looked at the preparation of
an ionic liquid (Scheme 1). Conventional synthesis of
ionic liquids has several disadvantages. First, long reflux
times are often needed to obtain reasonable yields. Also,
the purification of the ionic liquid is often problematic
and large quantities of organic solvents are required to
extract impurities. This is especially true with halide
[video 7]. Performing the reaction using water as a
solvent the decomposition of AIBN is again clearly seen
as is the onset of polymerization, this time after approx-
imately 25 s of microwave irradiation. The polymeriza-
tion reaction is complete after a total time of 45–50 s
had elapsed [video 8] (Scheme 3).
7
O
O
MW
MW
O K
-
+
O
Br
Pr
N
N
+
N
N
+
Br
toluene
KOH, EtOH / H2O
Scheme 1.
Scheme 2.

M. D. Bowman et al. / Tetrahedron Letters 49 (2008) 195–198
197
O
the solvent meniscus is observed and then this is
followed by significant arcing. At this point the input
of microwave power was stopped manually. In this case
the vessel did not fail since the pressure inside the tube
was not excessive. The camera allows reactions in which
arcing is a possibility to be closely monitored and
stopped before vessel failure.
MeO
O
MW
OMe
+
AIBN
n
+
MW
N
N
N
N
N2
N
In summary, we show here that, by interfacing a digital
camera with a scientific microwave unit, it is possible to
monitor macroscopic effects as reactions proceed. These
include color and viscosity changes, evolution of gases,
metal-mediated couplings and arcing. The application
of the apparatus to these and other reactions and the
ability to see a reaction as it runs is something that will
aid chemists in performing their microwave-promoted
chemistry.
Scheme 3.
Transition metal-catalyzed reactions can be performed
very efficiently using microwave heating and palla-
dium-mediated reactions have attracted particular atten-
tion.1 For this reason, and because it is a more
challenging reaction to probe, we included a Suzuki cou-
2
1
3
pling in our study. We have shown previously that
Suzuki reactions can be performed using water as the
solvent, ppm levels of a ligandless palladium salt as
the catalyst, sodium carbonate as base, and tetrabutyl-
ammonium bromide as a phase-transfer agent.14 The
mixture is heated to 150 ꢁC and the reaction is complete
within the period of 1–3 min, depending on the substrate
used. Using these conditions, we performed the coupling
Acknowledgments
CEM Corporation is thanked for provision of micro-
wave apparatus and camera. Funding from the Univer-
sity of Connecticut is acknowledged.
0
of 4 -bromoacetophenone and phenylboronic acid with
the in situ camera monitoring (Scheme 4). First we ran
the reaction without stirring [video 9]. When the reac-
tion mixture is placed into the microwave cavity it is
cloudy. Within 20 s of microwave heating, a layer forms
on the top of the water and it appears that the reaction is
taking place there. Upon cooling at the end of the reac-
tion, the product crystallizes out on top of the water
layer. A 95% yield of 4-acetylbiphenyl was obtained.
When the reaction is run with stirring, again a second
phase forms upon heating and, at the end of the reaction
the product crystallizes out on top of the water layer
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2
007.10.097.
References and notes
. (a) A number of books have been published recently. See:
[
video 10]. The product yield was comparable regardless
of whether the reaction mixture was or was not stirred.
1
Microwaves in Organic Synthesis; Loupy, A., Ed.; Wiley-
VCH: Weinheim, 2006; (b) Kappe, C. O.; Stadler, A.
Microwaves in Organic and Medicinal Chemistry; Wiley-
VCH: Weinhiem, 2005.
One safety issue when using metal catalysts in conjunc-
tion with microwave heating is that deposition of metal
on the surface of a glass tube can lead to arcing and
superheating. This in turn can result in localized melting
of the glass and a pinhole fracture of the tube. If the
contents of the vessel are under pressure, a small frac-
ture can lead to a catastrophic destruction of the tube.
While metal deposition is not a major issue when using
low levels of metal catalysts, as the concentration
increases so does the potential for an issue. To illustrate
this, we heated a solution of palladium acetate in tolu-
ene using a microwave power of 150 W and monitored
the effects using the camera [video 11]. To accentuate
any effects, the mixture was not stirred. The formation
of metallic palladium is observed after 3.5 min together
with some observable superheating. After 4 min, deposi-
tion of palladium metal on the surface of the glass above
2. Pivonka, D. E.; Empfield, J. R. Appl. Spectrosc. 2004, 58,
41.
3. (a) Leadbeater, N. E.; Smith, R. J.; Barnard, T. M. Org.
Biomol. Chem. 2007, 822; (b) Leadbeater, N. E.; Smith, R.
J. Org. Lett. 2006, 8, 4589; (c) Barnard, T. M.; Leadbeater,
N. E. Chem. Commun. 2006, 3615.
4
5
. King, E. E. U.S. Patent: US 2007/0062934 A1.
. Microwave reactions were conducted using a commer-
cially available monomode microwave unit (CEM Dis-
cover S-class). A 1.3 megapixel camera was interfaced with
the microwave unit by means of an access port in the side
of the microwave cavity. The face of the lens was
positioned outside the cavity wall and protected with a
plastic cover. Three white light LEDs were placed at the
bottom of the microwave cavity to illuminate the reaction
vessel. The use of external lighting meant that it was also
necessary to have a means for preventing the illumination
source from saturating the infrared temperature detector.
The camera was connected to a PC via an USB 2.0
interface and controlled using computer software. Using
this, it was possible to record temperature, pressure, and
microwave power profiles at the same time as the video
images.
COMe
MW, [Pd]
+
Ph B(OH)2
Ph
COMe
H2O, TBAB
Na2CO3
Br
Scheme 4.

198
M. D. Bowman et al. / Tetrahedron Letters 49 (2008) 195–198
6
. For a review on the concepts see: Gabriel, C.; Gabriel, S.; nitrogen gas occurred when the bulk temperature of the
Grant, E. H.; Halstead, B. S.; Mingos, D. M. P. Chem.
Soc. Rev. 1998, 27, 213.
. In a 10 mL glass tube were placed N-methylimidazole
reaction mixture reached 72 ꢁC, this being followed by a
significant increase in viscosity as polymerization
occurred. The reaction was repeated using identical
reaction conditions but with the addition of water
(1 mL) to the tube prior to sealing.
7
(
6
0.25 mL, 3.14 mmol), 1-bromopropane (0.60 mL,
.61 mmol), and toluene (1.0 mL). The tube was sealed
with a septum and placed into the microwave cavity.
Using an initial microwave power of 300 W, the reaction
mixture was heated to a target temperature of 160 ꢁC and
held there until a total time of 5 min had elapsed. Upon
cooling to room temperature, the ionic liquid product was
isolated by decanting, washed with ethyl acetate
12. For a recent review see: Olofsson, K.; Nilsson, P.; Larhed,
M. In Microwaves in Organic Chemistry; Loupy, A., Ed.;
Wiley-VCH, 2006, Chapter 15, p 685.
0
13. In a 10 mL glass tube were placed 4 -bromoacetophenone
(199 mg, 1.0 mmol), phenylboronic acid (122 mg,
1.0 mmol), Na CO (392 mg, 3.7 mmol), tetrabutylammo-
2 3
(
2 · 5 mL) and its identity confirmed by comparison of
nium bromide (322 mg, 1.0 mmol), palladium stock solu-
tion (0.5 mL of a 20 ppm solution in water), and water
(1.5 mL) to give a total volume of water of 2 mL and a
total palladium concentration of 5 ppm. The vessel was
sealed with a septum and placed into the microwave
cavity. Using an initial microwave power of 150 W, the
reaction mixture was heated to a target temperature of
150 ꢁC and held there until a total reaction time of 5 min
had elapsed. The reaction was repeated using identical
reaction conditions but with the addition of a magnetic
stir bar to the tube prior to sealing. After allowing the
mixture to cool to room temperature, the reaction vessel
was opened and the contents poured into a separating
funnel. Water (30 mL) and ethyl acetate (30 mL) were
added and the organic material extracted and removed.
After further extraction of the aqueous layer with ethyl
acetate, combining the organic washings and drying them
NMR data with that in the literature.
8
9
. See, for example: (a) Varma, R. S.; Namboodiri, V. V.
Chem. Commun. 2001, 643; (b) Khadilkar, B. M.; Rebeiro,
G. L. Org. Process. Res. Dev. 2002, 6, 826; (c) Deetlefts,
M.; Seddon, K. R. Green Chem. 2003, 5, 181.
. In a 10 mL glass tube containing a magnetic stir bar were
placed ethyl benzoate (0.25 mL, 1.74 mmol), KOH
(
(
0.5 mL of a 3 N solution in water, 1.5 mmol), ethanol
0.5 mL), and phenolphthalein solution (0.1 mL). The tube
was sealed with a septum and placed into the microwave
cavity. Using an initial microwave power of 200 W, the
reaction mixture was heated to a target temperature of
1
20 ꢁC and held there until the color of the solution
changed from purple to colorless (35–40 s).
1
1
0. For a recent review see: Hoogenboom, R.; Schubert, U. S.
Macromol. Chem. Rapid Commun. 2007, 28, 368.
1. In a 10 mL glass tube containing a magnetic stir bar were
placed methyl acrylate (2.0 mL, 22.2 mmol) and AIBN
4
over MgSO , the ethyl acetate was removed in vacuo
leaving the crude product, which was isolated and
characterized by comparison of NMR data with that in
the literature.
(
6.0 mg, 36.5 lmol). The tube was sealed with a septum
and placed into the microwave cavity. Using an initial
microwave power of 150 W, the reaction mixture was
heated to a target temperature of 80 ꢁC and held there
until a total time of 90 s had elapsed. Evolution of
14. Arvela, R. K.; Leadbeater, N. E.; Sangi, M. S.; Williams,
V. A.; Granados, P.; Singer, R. S. J. Org. Chem. 2005, 70,
161.