Microwave-Induced Esterification Using Heterogeneous Acid Catalyst in a Low Dielectric Constant Medium

Full text of DOI:10.1021/jo990515c

1210
J . Org. Chem. 2000, 65, 1210-1214
can be overcome by the use of a monomode applicator,
Micr ow a ve-In d u ced Ester ifica tion Usin g
capable of focusing electromagnetic waves with the use
of a waveguide to achieve a homogeneous electromag-
inetic field.3 However, despite the advantages, such
equipment remains relatively unavailable in contempo-
rary organic synthesis laboratories.
Heter ogen eou s Acid Ca ta lyst in a Low
Dielectr ic Con sta n t Med iu m
Konrad G. Kabza,* Brian R. Chapados,
J ason E. Gestwicki, and J essica L. McGrath
Concomitant with the technological advances in mi-
crowave reactors, several strategies for microwave-as-
Department of Chemistry, State University of New York
College at Fredonia, Fredonia, New York 14063
sisted organic synthesis are currently in use.1-4,11
A
significant body of work concerning the applications of
microwave radiation to homogeneous reactions exists.2-4
However, heterogeneous reactions, in particular those
that involve the use of solid-state catalysts, are particu-
larly advantageous in terms of ease of use, separation,
and catalytic recycling.12 Most reports of kinetic studies
involving the use heterogeneous catalysts in microwave-
irradiated systems, suggest that selective superheating
of the catalyst may account for observations of small rate
enhancements.13-16
To effectively study the kinetics of a heterogeneous
system, absorption of microwave radiation should be
limited only to the reacting species. This can be ac-
complished through the use of a low dielectric constant
medium (i.e., hydrocarbons) as a reaction solvent.17
Additionally, the reaction should occur entirely inside the
microwave cavity to maximize irradiation of all reacting
species. This constraint poses severe practical limitations,
since adequate temperature and pressure control in such
a system is difficult to achieve.17 To overcome this
problem, we have developed a continuous-flow reactor for
heterogeneous systems, which localizes a bed of Am-
berlyst-15 cation-exchange resin contained in a radiolu-
cent polyethylene tube inside the microwave cavity
(Figure 1).
We have chosen the acid-catalyzed Fischer-type esteri-
fication of isopentyl alcohol and acetic acid as our model
system. Esterifications are of practical interest because
esters are used in the production of a wide range of
products such as cosmetics, lubricants, pharmaceuticals,
and plasticizers. This reaction represents a well-under-
stood Fischer esterification that in homogeneous systems
occurs by the AAC2 mechanism18 (Scheme 1). Since the
reaction is driven by the protonation of the carbonyl
functionality, reacting species should be localized to the
bed of acid catalyst, subject to microwave radiation. This
model is also advantageous to study because all reagents
Received March 23, 1999
In tr od u ction
During the past decade, our knowledge of microwave-
assisted organic synthesis has increased significantly.1-4
Initial studies of several reactions revealed an enhance-
ment of reaction rates in the presence of microwave
irradiation, as compared to identical reactions heated by
classical methods. Early hypotheses suggested that the
rate enhancements were due to athermal effects induced
by microwave radiation.5a-e However, subsequent inves-
tigations, in which reaction mixtures were stirred or
mixed to ensure thermal homogeneity, revealed that
reaction rates of microwave-irradiated and classically
heated reactions were comparable.6a-c These studies led
to the hypothesis that rate enhancement observed as a
result of microwave irradition is caused by superheating
of the reaction solution.7,8
Despite limitations, domestic microwave ovens are
widely used for laboratory organic synthesis.1 These
devices are multimode applicators, which operate at a
fixed maximum power level for varying periods of time
(duty cycle). The resulting electric field is thus nonuni-
form or heterogeneous, resulting from multiple reflections
inside the microwave cavity. Efforts to model the elec-
tromagnetic field inside such reactors reveals the fact
that temperature measurement of an irradiated sample
cannot be easily determined.9-10 These underlying factors
are a large cause of variation in reported rate enhance-
ments. The limitations of the domestic microwave oven
(1) Loupy, A.; Petit, A.; Hamelin, J .; Texier-Boullet, F.; J acquault,
P.; Mathe, D. Synthesis 1998, 1213-1234.
(2) Stuerga, D. A. C.; Gaillard P. J ournal of Microwave Power and
Electromagnetic Energy, 1996, 31, 87-100.
(3) Strauss, C. R.; Trainor, R. W., Aust. J . Chem. 1995, 48, 1665-
1692.
(4) Westaway, K. C.; Gedye, R. N., J . Microwave Power Electromag.
Energy. 1995, 30, 219-230.
(5) (a) Pollington, D. S.; Bond, G.; Moyes, R. B.; Whan, D. A.;
Candlin, J . P.; J ennings, J . R. J . Org. Chem. 1991, 56, 1313. (b)
Thiebaut, J . M.; Roussy, G.; Maire, G.; Garin, F. International
Conference on High-Frequency Microwave Processing and Heating,
Arnhem, The Netherlands, 1989. (c) Berlan, J .; Giboreau, P.; Lefeuvre,
S.; Marchand, C. Tetrahedron Lett. 1991, 32, 2363. (d) Sun, W.-C.;
Guy, P. M.; J ahngen, J . H.; Rossomando, E. F.; J ahngen, E. G. E. J .
Org. Chem. 1988, 4414. (e) Bose, A. K.; Manhas, M. S.; Ghosh, M.;
Raju, V. S.; Tabei, K.; Urbanczyk-Lipkowska, Z. Heterocycles 1990, 30,
741.
(6) (a) Raner, K. D.; Strauss, C. R.; Vyskoc, F.; Mokbel, L. J . Org.
Chem. 1993, 950. (b) Laurent, R.; Laporterie, A.; Dubac, J .; Berlan,
J .; Lefeuvre, S.; Audhuy, M. J . Org. Chem. 1992, 57, 7099. (c) J ahngen,
E. G. E.; Lentz, R. R.; Pesheck, P. S.; Sackett, P. H. J . Org. Chem.
1990, 55, 3406.
(9) (a) Stuerga, D.; Gaillard P. Tetrahedron 1996, 52, 5505-5510.
(b) Berlan, J . Radiat. Phys. Chem. 1995, 45, 581-589.
(10) (a) Ayappa, K. G. Reviews in Chemical Engineering 1997, 13,
1-69. (b) Saillard, R.; Poux, M.; Berlan, J .; Audhuypeaudecerf, M.
Tetrahedron 1995, 51, 4033-4042.
(11) Kingston, H. M.; Haswell, S. J . Microwave-Enhanced Chemistry;
Fundamentals, Sample Preparation and Applications; American Chemi-
cal Society: Washington, D.C., 1997; pp 16-17.
(12) Xu, Z. P.; Chuang, K. T. Can. J . Chem. Eng. 1996, 74, 493-
500.
(13) Gedye, R. N.; Wei, J . B. Can. J . Chem. 1998, 76, 525-532.
(14) Shibata, C.; Kashima, T.; Ohuchi, K. J pn. J . Appl. Phys. 1996,
35, 316.
(15) Chemat, F.; Esveld, D. C.; Poux, M.; Di-Martino, J . L. J .
Microwave Power Electromag. Energy 1998, 33, 88-94.
(16) Holzwarth, A.; Lou, J .; Hatton, T. A.; Laibinis, P. E. Ind. Eng,
Chem. Res. 1998, 37, 2701-2706.
(17) Mingos, D. M. P. Chem. Ind. 1994, 1 Aug, 596-599.
(18) March, J . Advanced Organic Chemistry: Reactions, Mecha-
nisms, and Structure; Wiley: New York, 1992; pp 378-383.
(7) (a) Kingston, H. M.; J assie, L. B. Introduction to Microwave
Sample Preparation Theory and Practice; American Chemical Soci-
ety: Washington, D.C., 1988. (b) Baghurst, D. R.; Mingos, D. M. P. J .
Chem. Soc., Chem. Comm. 674, 1992.
(8) Mingos, D. M. P. Res. Chem. Intermed. 1994, 20, 85.
10.1021/jo990515c CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/03/2000

Notes
J . Org. Chem., Vol. 65, No. 4, 2000 1211
Ta ble 2. Ra te Con sta n ts for th e P r od u ction of Isoa m yl
Aceta te vs Ca ta lyst Wa ter Con ten t
catalyst water contenta
rate constantb (k/min-1
)
0
5
10
20
2.3 × 10-1
1.8 × 10-1
1.2 × 10-1
8.2 × 10-2
a
b
Water content is reported in % (w/w). Rate constants were
determined using a Langmuir-Hinshelwood model.12
Ta ble 3. Ca ta lyst Wa ter Con ten t Mea su r ed by TGA
calcd catalyst
water contenta
actual catalyst
water contentb
dry
5
1.5
7c
10
20
9
18
F igu r e 1. Continuous flow setup for esterification of isopentyl
alcohol and acetic acid using microwave radiation.
a
Water content is reported in % (w/w), calculated from the
Sch em e 1. P r op osed Mech a n ism for th e
Acid -Ca ta lyzed Ester ifica tion of Isop en tyl Alcoh ol
w ith Acetic Acid ; AAC2 Mech a n ism Is P r efer r ed for
Rea ction s w ith Sm a ll R Gr ou p s a n d Little Ster ic
Hin d r a n ce9
weight change upon addition of water to the resin. Dry resin was
b
taken directly out of vacuum sealed package. Water content
measured by isothermal gravimetric analysis (TGA). c Sample size
was only 5 mg, compared to an average of 30 mg for all other
samples.
Ta ble 1. Con tr ol Exp er im en t To Com p a r e Ca ta lytic
Efficien cy of Ion -Exch a n ge Resin to Aqu eou s Su lfu r ic
Acid
F igu r e 2. Enlargement of polyethylene reaction tube contain-
ing Amberlyst-15 cation-exchange resin.
trial
isoamyl acetate (mg/mL)a
1
2
190.2 ( 7.8b
192.2 ( 18.5c
a point of studying progressively hydrated catalysts. In
principle, water present in the catalystic resin could
facilitate superheating of the resin, leading to an in-
creased reaction rate under microwave radiation. In
addition, the presence of water could facilitate proton
transfer and thus influence the reaction kinetics. To test
the effect of water contained within the resin upon
reaction progress, we measured rates of reactions heated
by microwave radiation and classical heating, in the
presence of catalytic resin loaded with varying amounts
of water.
a
b
Average of time points (10, 20, 30, 60). Reactions were
performed using 2.6 mL of concentrated sulfuric acid (42.5 mequiv
H+). c Reactions were performed using 20.0 g (wet weight) of AG
SOW-X8 resin (42.5 mequiv H+).
and products are soluble in hexane (low dielectric con-
stant). The product, isoamyl acetate, is also easily as-
sayed by gas chromatography.
Amberlyst-15 was shown previously12 to be an effective
catalyst for the Fischer-type synthesis of esters in a
heterogeneous, aqueous system. In fact, to compare the
Amberlyst-15 catalytic activity with that of liquid H2SO4,
we have performed a control experiment (Table 1), which
indicated similar efficiences in ester formation for both
hetero- and homogeneous systems. A strictly water-free
system for Fischer-type esterification is unattainable.
Even the factory-dried Amberlyst-15 resin contains traces
of moisture (Tables 2 and 3). In addition, the resin is
highly hygroscopic and readily adsorbs water from the
air upon short exposure to ambient conditions.
Exp er im en ta l Section
Gen er a l In for m a tion . The experimental setup (Figures 1
and 2) was a closed system consisting of a polyethylene reaction
tube, Teflon tubing (4.5 mm i.d.), and a glass reaction vessel.
Teflon and polyethylene were used inside the microwave to
ensure transparency toward microwave radiation.11 A purge
valve was installed in the external reaction vessel to maintain
constant ambient pressure inside the system.
All esterification reactions were run at 40 ( 3 °C in nondis-
tilled hexane (Fischer). The total volume of the system was 120
mL, and the flow rate of the reaction mixture was held constant
at 88 mL/min. Gas chromatography data was collected using a
GOW-MAC (GC series 350) gas chromatograph connected to an
integrator (HP 3390A).
In studies of microwave-assisted chemical conversions
it is important to concentrate on possible factors influ-
encing reaction progress. Since 2.45 GHz microwaves are
“tuned” to heat water with high efficiency, we have made

1212 J . Org. Chem., Vol. 65, No. 4, 2000
Notes
The microwave oven used was a commercially available model
(General Electric J ES-0601T) operating at a maximum power
level of 650 W. The oven was equipped with a digital timer and
could be operated at 10 different power levels. Domestic micro-
wave ovens operate by alternating from maximum power to zero
power in timed cycles (duty cycles).7a The frequency of the
maximum power cycle is represented by a power level number.
For example, power level 2 means that the magnetron is actually
on for an average of 2 s out of every 10 s, and power level 10
represents continuous radiation.
Ad d ition of Wa ter to Ca ta lytic Resin . Amberlyst-15
cation-exchange resin (20.0 g, Aldrich) was spread out in a large
weighing dish to maximize surface area. The dish was placed
on a raised platform inside a sealable, cylindrical container
partially filled with water. The catalytic resin was allowed to
adsorb water from the vapor-saturated environment. The water
content of the resin was verified by analyzing samples using
isothermal gravimetric analysis (Dupont 951 Thermogravimetric
Analyzer) (Table 3).
F igu r e 3. Comparison of conventionally heated (9) and
microwave-irradiated ([) reactions. Each point represents the
average of three experiments. Error bars represent one
standard deviation.
Ester ifica tion of Isop en tyl Aceta te a n d Acetic Acid .
Hexane (93.6 mL) was pumped into the system and allowed to
circulate for 2 min under ambient conditions. Isoamyl alcohol
(12.0 mL, Aldrich) was added to the external flask (Figure 2)
and allowed to circulate for 30 s. Glacial acetic acid (14.4 mL,
Fischer) was added, and the microwave turned on. The initial
power level setting was 2, but this setting was alternated
between 2 and 1, to maintain a constant temperature of 40 ( 3
°C as monitored by a digital thermometer (Digi-thermo, quartz)
placed in the external flask. Since multimode applicators are
only capable of producing maximum power electromagnetic
fields, alternating between power level settings 1 and 2 produced
a “virtual power level” of 1.3-1.6 (estimated). The reaction
progress was followed by extracting 1.0 mL aliquots from the
external flask every 10 min, for 1 h. Aliquots were flushed
through columns containing Amberlite CG-400 anion-exchange
resin (100-200 mesh, chromatographic grade, Mallinckrodt) to
remove residual acetic acid and stop the reaction, and 1 µL
samples were analyzed by gas chromatography.
Conventional heating was accomplished by submerging the
reaction vessel in a constant temperature water bath maintained
at 56 °C, which resulted in a solution temperature of 40 ( 1 °C
as monitored in the external flask. All analytical procedures used
to prepare solutions for both of the processes (thermal and
microwave heating) were identical.
Ga s Ch r om a togr a p h ic An a lysis. The reaction products
were separated using a 20% DC200 (on chrom) column (80/100
mesh). The operating conditions for the gas chromatograph were
associated with multimode microwave reactors. Further-
more, this result supports the finding of several others
that if the thermal effects of microwave radiation are
eliminated, reaction rates are comparable to those of
classically heated systems.
This result is interesting, because while our results
agree with previous findings for homogeneous systems,
our understanding of heterogeneous systems is less
complete. One might predict that superheating of the
catalyst bed could create localized thermal gradients that
would influence the reaction rate but be virtually unde-
tctable by measurement of the temperature at the outlet.
This phenomenon was reported by Chemat et al. for
esterification reactions performed in a continuous mi-
crowave reactor, catalyzed by Fe2(SO4)3 adsorbed onto
Montmorillonite clay, localized inside the microwave
cavity.15
Further evidence for selective superheating of solid
supports was reported by Gedye et al., who propose that
solid CuCl (strongly absorbs microwave radiation) present
in the addition reaction of CCl3CO2CH2CH3 and CCl4 to
styrene result in rapid heating of the reaction, thus
accounting for the observed rate enhancement.13
Shibata et al. recently reported a reduction in activa-
tion energy in the microwave-assisted decomposition of
sodium bicarbonate in water, attributing the result to
nonthermal microwave effects.14 However, as Gedye et
al. point out, the presence of solid sodium bicarbonate
suspension (20%) in solution may have resulted in
selective heating of the solid, thus accounting for the
apparent decrease in activation energy.13 This critical
observation is supported by a recent report that indicates
that the microwave heating of nonpolar solvents can be
increased by the addition of magnetic nanoparticles.16
Amberlyst-15 strongly absorbs microwave radiation
and will readily melt if irraditated at power level 10 for
more than 2 min. In addition, if the catalytic resin is
omitted from the reactor system, absorption of microwave
radiation is significantly reduced (data not shown),
suggesting that the catalytic resin is absorbing a large
amount of the microwave radiation during the reaction.
These results prompted us to test whether preloading
the catalyst with small amounts of a polar solvent would
facilitate selective superheating of the resin, resulting
in a rate enhancement. Since microwave radiation is
strongly absorbed by polar species, it follows that the
presence of additional water associated with the catalytic
resin could induce the formation of thermal gradients in
injector: 180 °C
detector: 160 °C
oven: 139 °C
approximate retention times:
hexanes: 0.8 min.
isoamyl acetate: 2.5 min.
isopentyl alcohol: 3.5 min.
flow rate: He, 50 mL/min
The injection size of all samples was 1 µL. The approximate
retention times for the three components are shown above.
Resu lts a n d Discu ssion
Effective rate comparison of microwave and classically
heated reactions is complicated by a variety of factors.
These typically include microwave absorption by polar
solvents, superheating, ineffective mixing, and inacurrate
temperature measurement. We used a nonpolar solvent
in a heterogeneous, continuous-flow system in an attempt
to minimize solvent absorption and superheating, while
maximizing the microwave absorption by reacting spe-
cies.
No comparable difference between reaction rates of
microwave-mediated and classically heated reactions was
observed (Figure 3). Although our system did not utilize
a monomode reactor, the reproducibility and precision
of our results from both microwave and classically heated
reactions at the same temperature serve as an indication
that our appartus eliminates some of the typical problems

Notes
J . Org. Chem., Vol. 65, No. 4, 2000 1213
Ta ble 4. Yield Com p a r ison s for Isoa m yl Aceta te
% difference,
water
content
(%)
homogeneous calc heterogeneous heterogeneous vs
theoretical yielda
(mg/mL)
exptl yieldb
(mg/mL)
homogeneous
reactionsc
dry
5
10
20
106
80
62
105
104
93
0
30
50
76
40
71
a
Theoretical yield for a homogeneous system was calculated
using initial concentrations of isopentyl alcohol and acetic acid
and comparable equivalents of aqueous acid. The amount of water
present in the resin was assumed to be added directly to the
b
reaction solution. Actual experimental yield for the heteroge-
neous system described in the Experimental Section. c The percent
difference represents the variance of the experimental yields (from
heterogeneous reaction) compared to the calculated theoretical
yields for a homogeneous reaction.
F igu r e 4. Comparison of varying degrees of Amberlyst-15
water content in reactions heated by microwave radiation.
Diamonds (() represent dry resin; squares (9) represent 5%
water content by mass; triangles (2) represent 10% water by
mass; and circles (b) represent 20% water content by mass.
Each point represents the average of three experiments. Error
bars represent one standard deviation.
ment, water is free to diffuse into and out of the resin,
creating a quasi-homogeneous system and thus satisfying
the proposed kinetic model.12 However, in our system,
the nonpolar nature of hexane could prevent water
molecules present in the pores of the resin from escaping,
blocking access to sulfonic acid groups. This overall lack
of accessibility to the resin would cause a decrease in
reaction rate. This prediction is consistent with studies
of water hydration in Amberlyst-15 resin that suggest
the presence of a constant amount of bulk water present
in the pores of the resin.19
On the basis of the fact that the esterification reaction
is a reversible one, as described in eqs 1 and 2, the
CH3COOH + (CH3)2CHCH2CH2OH yk1z
k-1
F igu r e 5. Comparison of varying degrees of Amberlyst-15
water content in reactions heated by conventional water bath.
Diamonds (() represent dry resin; squares (9) represent 5%
water content by mass; triangles (2) represent 10% water by
mass; and circles (b) represent 20% water content by mass.
Each point represents the average of three experiments. Error
bars represent one standard deviation.
(CH3)2CHCH2CH2OOCCH3 + H2O (1)
[(CH3)2CHCH2CH2OOCCH3][H20]
Keq
)
) 6.2 (2)
[CH3COOH][(CH3)2CHCH2CH2OH]
presence of extra water in hydrated catalytic resins (5%,
10%, 20% w/w) could shift the equilibrium toward the
reactants. This, however, is not supported by experimen-
tal findings as compiled in Table 4. In fact, these data
indicate that the more hydrated resins are more efficient
in product ester formation than would be expected for
an idealized homogeneous system. These results indicate
the complexity of dealing with the kinetics of a hetero-
geneous system and suggest an interesting starting point
for future studies.
the catalytic resin, leading to superheating and an
increased reaction rate. Surprisingly, we observed that
increasing the amount of water present within the
catalytic resin significantly decreased the reaction rate,
regardless of the method of energy input (Figures 4 and
5). This result indicates that the ability of water to
enhance the formation of thermal gradients is not the
most important factor controlling the reaction rate in
this system. In fact, the data graphically represented
in Figure 4 provided us with numerical values com-
puted from the initial (linear) portions of the curves in
accordance to a Langmuir-Hinschelwood model (Table
2). Obtained rate constants were on the same order as
those reported by Xu et al., who used a fully aqueous
system.12
Previous studies on the esterification of acetic acid and
methanol in a heterogeneous, aqueous system suggest
that such a system can be treated as homogeneous for
the purpose of kinetic measurement.12 This treatment
assumes that absorption by the resin, Amberlyst-15, is
weak for all components. We have empirically observed
that absorption of water and other solvents by Amberlyst-
15 causes the resin to swell up to several times its normal
size. This is caused by solvent molecules entering the
porous space within the resin. In an aqueous environ-
Con clu sion s
In conclusion, we have found that our model hetero-
geneous esterification reaction behaves comparably under
both microwave and thermal conditions. Furthermore,
the presence of water in the catalytic resin caused an
overall reduction in the reaction rate, independent of the
type energy input. These findings provide further evi-
dence that if the reaction mixture is thoroughly circu-
lated, chemical reactions seem to behave similarly re-
gardless of the source of energy that drives them. These
data support our previous studies, which also indicated
a lack of energy type preference for the reaction kinet-
(19) Toteja, R. S. D.; J angida, B. L.; Sundaresan, M.; Venkatara-
mani, B. Langmuir 1997, 13, 2980-2982.

1214 J . Org. Chem., Vol. 65, No. 4, 2000
Notes
ics.20 Although we had no method of testing for the
selective superheating of the reaction solution or the
catalytic resin, if superheating did occur, it had no effect
on the reaction rate. Further study of a similar system
in a monomode reactor and a more accurate method of
temperature measurement within the solid-state catalyst,
such as an infrared sensor/camera or thermocouple, are
needed before a difinitive conclusion can be reached.
These data, coupled with kinetic studies of macroreticular
resins in a microwave environment, will further our
understanding of heterogeneous microwave catalysis.
Ack n ow led gm en t. We would like to thank SUNY
and the SUNY Fredonia Chemistry Department for
financial support of this research.
(20) Kabza, K. G.; Gestwicki, J . E.; McGrath, J . L.; Petrassi, H. M.
J . Org. Chem. 1996, 61, 9599-9602.
J O990515C