Equilibrium Reactions in Supercritical Difluoromethane

Article abstract of DOI:10.1021/jp0377026

A dielectometry technique is used to follow the extent of two equilibrium reactions in supercritical difluoromethane (se HFC32), and the validity of the technique is demonstrated in the liquid state and compared to results obtained using gas chromatography-mass spectroscopy (GC-MS). The apparent equilibrium constant for the acid-catalyzed esterification of benzoic acid with 1-butanol decreased as the pressure increased, and this was proposed to be due to clustering at lower solvent density. In supercritical carbon dioxide (sc CO ₂), the equilibrium constant was similar to that in se HFC32, despite the large difference in the dielectric constant of the fluids. The solute had a significant effect on the solution dielectric constant, such that the two solutions were similar. An acid-catalyzed aldol condensation reaction was also studied, and the apparent equilibrium constant was observed to change in a manner similar to that observed for the esterification reaction. The overall change in equilibrium constant was less than that observed for the esterification reaction and this was rationalized, in terms of the different dipole moments of the reagents in the two reactions.

Full text of DOI:10.1021/jp0377026

4922
J. Phys. Chem. B 2004, 108, 4922-4926
Equilibrium Reactions in Supercritical Difluoromethane
Andrew P. Abbott,*,† Stuart Corr,‡ Nicola E. Durling,† and Eric G. Hope†
Chemistry Department, UniVersity of Leicester, Leicester, LE1 7RH, United Kingdom, and Ineos Fluor,
Runcorn Technical Centre, The Heath, Runcorn, Cheshire, WA7 4QD, United Kingdom
ReceiVed: December 4, 2003; In Final Form: February 13, 2004
A dielectometry technique is used to follow the extent of two equilibrium reactions in supercritical
difluoromethane (sc HFC32), and the validity of the technique is demonstrated in the liquid state and compared
to results obtained using gas chromatography-mass spectroscopy (GC-MS). The apparent equilibrium constant
for the acid-catalyzed esterification of benzoic acid with 1-butanol decreased as the pressure increased, and
this was proposed to be due to clustering at lower solvent density. In supercritical carbon dioxide (sc CO2),
the equilibrium constant was similar to that in sc HFC32, despite the large difference in the dielectric constant
of the fluids. The solute had a significant effect on the solution dielectric constant, such that the two solutions
were similar. An acid-catalyzed aldol condensation reaction was also studied, and the apparent equilibrium
constant was observed to change in a manner similar to that observed for the esterification reaction. The
overall change in equilibrium constant was less than that observed for the esterification reaction and this was
rationalized, in terms of the different dipole moments of the reagents in the two reactions.
Introduction
O’Shea et al.6 probed the hydrogen bonding and polar
interactions in sc ethane, fluoroform, and CO2 by measuring
the tautomeric equilibrium of 4-(phenylazo)-1-naphthol in these
solvents. The less-polar tautomer was dominant in ethane,
almost-equal amounts of the tautomers were observed in CO2,
and in fluoroform, the more-polar tautomer was observed to be
dominant. These shifts in equilibrium composition favoring the
more-polar tautomer were attributed to the large quadrupole
moment of CO2 and hydrogen-bond donor ability of fluoroform.
From these results, it is suggested that pressure can be used to
control processes that involve polar molecules in some super-
critical fluids.
The recent growth in the use of supercritical (sc) fluid solvents
as media for chemical synthesis1 has inspired several research
groups to examine chemical equilibria to probe intermolecular
interactions in supercritical fluids. Solvents influence reaction
thermodynamics through the environment produced around the
solute. Among the most important solvent properties that
characterize this reaction environment are the polarity and the
polarizability. The solvent polarity corresponds to the permanent
dipole-dipole interactions, whereas polarizability is indicative
of inductive forces, where the solute molecule induces a dipole
in the solvent. Thus, measuring pressure effects on equilibria
in supercritical fluids can give insight into molecular interac-
tions.
Kimura and co-workers2-4 addressed the issue of how fluid
structure influences chemical reactions by examining the effect
of solvent density on the equilibrium constant for the dimer-
ization of 2-methyl-2-nitrosopropane in CO2, CClF3, CHF3,
argon, and xenon. The results showed that the equilibrium
constant in CO2, CClF3, and CHF3 increased as the density in
the gas phase decreased in the low-density supercritical region
and then increased again as the density was increased. It was
suggested that these observations were due to the different
dominant molecular interactions of the fluid within each of these
density regions.
Studies in the literature on aldol and esterification reactions
in supercritical fluids are very limited. Ikariya and co-workers
reported the catalytic asymmetric Mukaiyama aldol reaction of
a ketene silyl acetal of thioester in sc CHF3 and CO2.7 The
reaction proceeded to give the silylated aldol product in
moderate yields. The yield and enantioselectivity of the reaction
were influenced by the solvent used. A maximum in enantio-
selectivity and yield of 88% and 46%, respectively, was
observed for the reaction in sc CHF3. On comparison with CO2,
the reaction proceeded only slightly to give 8% of the aldol
product and also a reduced enantioselectivity of 72%. The low
yield in sc CO2 was reported to be due to its low polarity, which
results in low solubility of the acid catalyst in this medium.
Ellington and co-workers8,9 used UV-Vis spectroscopy to
find the apparent bimolecular rate constant for the esterification
of phthalic anhydride with methanol in sc CO2 at temperatures
of 313 and 323 K and pressures of 97.5-166.5 bar. This reaction
was chosen as a representative reaction between a dilute solute
(phthalic anhydride) and a typical co-solvent (methanol) in sc
CO2. At 313 K, the calculated bimolecular rate constants
exhibited a 4-fold increase with a decrease in pressure, from
145.8 bar to 97.5 bar. At 323 K, a 25-fold increase in the rate
constant was observed when the pressure was decreased from
166.5 bar to 97.5 bar. The enhanced reaction rate constants at
lower pressures were attributed to the local concentration of
Chemical equilibria have also been related to hydrogen
bonding in supercritical fluids. Gupta and co-workers5 studied
the hydrogen bonding between methanol and triethylamine in
sc SF6, where a pronounced solvent effect was observed. The
equilibrium for methanol-triethylamine association increased
as the pressure decreased toward the critical point, with the
pressure effect being most dominant around the critical point.
* Author to whom correspondence should be addressed. E. mail:
andrew.abbott@le.ac.uk.
† University of Leicester.
‡ Ineos Fluor, Runcorn Technical Centre.
10.1021/jp0377026 CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/17/2004

Equilibrium Reactions in sc HFC32
J. Phys. Chem. B, Vol. 108, No. 15, 2004 4923
methanol around the phthalic anhydride molecules exceeding
the average bulk methanol concentration. Using estimated local
densities and local compositions, it was shown that the observed
increase in rate constant could be accounted for.
The esterification of acetic acid and ethanol in compressed
CO2 was studied at 333 K over a range of pressures10 and found
to reach equilibrium in 3 h under supercritical conditions and
in 6 h under subcritical conditions. Results showed that the
apparent equilibrium constant (KX) increased as the pressure
increased in the gas phase and reached a maximum in the critical
region where the system becomes one phase. After the critical
point was passed, KX decreased as the pressure increased. The
observed increase in KX at low pressures was explained, with
respect to the degree of clustering/local density enhancement
at these pressures. At high pressures, where clustering is
insignificant, KX for the reaction was similar to that of the
reaction in the absence of CO2.
In the present study, we report the first equilibrium reactions
in supercritical difluoromethane (sc HFC32) (critical temperature
of Tc ) 78.1 °C; critical pressure of pc ) 57.8 bar). This solvent
has previously been shown to be useful, because of its high
dielectric constant11 and large polarizability change with pres-
sure.12,13 A recent study has also shown that HFC 32 is a strong
hydrogen-bond donor close to the critical pressure14 and has
demonstrated high solubility for polar aromatic solutes.15
Figure 1. Comparison of measured and calculated conversion for the
esterification reaction.
capacitance of the solution. For this to occur, the products also
must remain in solution as the reaction proceeds.
With these limitations in mind, the esterification reagents used
were benzoic acid, 1-butanol, and p-Tos acid as the catalyst.
Benzoic acid was observed to have a high solubility in sc HFC
32 (at 363 K and 100 bar, the solubility was 0.542 mol dm-3),
which is considerably in excess of the concentrations used in
these experiments (0.04 mol dm-3). The 1-butanol and p-Tos
acid were readily soluble in the solvents under the reaction
conditions.
The dielectrometry technique was used to monitor the solution
concentration of reagents in liquid dichloroethane (DCE),
because of its similar dielectric properties to HFC 32 (for DCE,
ꢀ ) 10.37 at 278 K; for HFC 32, ꢀ ) 8.99 at 363 K and 200
bar). The results were compared to those obtained using GC-
MS. The reaction was followed over a 2-h period, using
dielectrometry and GC-MS. Dielectrometry measurements were
measured in situ, and for the GC-MS measurements, 2-mL
aliquots of the reaction solution were taken. The actual reaction
conversion was obtained from the GC-MS results at specific
time intervals. The conversion value from the dielectrometry
measurements was calculated from knowledge of the final
conversion of the reaction, from GC-MS, and the capacitance
value at each time interval. The measured (GC-MS) and
calculated (dielectrometry) conversions for this esterification
reaction are shown in Figure 1. This figure shows that the
dielectometry readings correlate well with those from GC-MS,
signifying that the dielectrometry technique is suitable for
following the progress of this reaction.
Experimental Procedure
The high-pressure apparatus used in this study was the same
as that described previously.15 HFC 32 (Ineos Fluor, 99.99%)
and CO2 (BOC, 99.9%) were used as received. The esterification
of benzoic acid (Scientific and Chemical Supplies, Ltd., 98%)
with 1-butanol (Fisher, 98%), using p-toluenesulfonic (p-Tos)
acid as the catalyst, was performed using reagent concentrations
of 0.04 mol dm-3. The acid-catalyzed aldol condensation of
cyclohexanone (Aldrich, 98%) was performed using p-Tos acid
as the catalyst. All experiments were conducted at 363 K and
in the pressure range of 60-220 bar. The reactants were placed
into the doser and the acid catalyst was placed in the reaction
vessel. This was then heated to the desired temperature and
subsequently pressurized, forcing the reactants from the doser
into the reaction vessel. The total time taken for the vessel to
reach the reaction pressure was <1 min. The system was left
to react for the desired time and where applicable capacitance
measurements were taken. The products were trapped by
depressurization into a larger volume autoclave, which also
stopped the reaction and the products were analyzed by gas
chromatography-mass spectroscopy (GC-MS) (Perkin-
Elmer).
Results and Discussion
The esterification reaction was then performed in sc HFC 32
as the reaction solvent. It is assumed that this esterification
reaction follows the mechanism shown in Scheme 1. Using an
optical cell, it was visually observed that the reaction was
homogeneous under all conditions studied in this work. The
dielectrometry technique was used to follow the progress of
the benzoic acid esterification reaction as a function of time,
and the results are shown in Figure 2 at selected pressures. The
uncertainty of the conversion is no greater than (2%. Figure 2
shows that this dielectrometry technique is useful for following
equilibrium reactions, because the point at which the reaction
reaches equilibrium can be easily observed. This figure shows
that the reaction has reached equilibrium in 2 h or less, under
the conditions studied. The reaction was performed for up to 6
h without any appreciable change in yield. Therefore, in the
Esterification Reaction. It has previously been shown that
a dielectrometry technique can be used to determine the
solubility of solutes in supercritical fluids.15 Therefore, it is
logical that the same technique can be used to follow the changes
in solution concentration during a reaction, because it is a rapid,
in situ method for measuring capacitance changes of reaction
systems. Dielectrometry is not affected by solution concentra-
tion, high pressure, and turbidity restraints that are present with
spectroscopic techniques. However, note that there are some
limitations: (i) it can only be used with reagents that are readily
soluble, because accurate capacitance measurements can only
be obtained in homogeneous solutions, and (ii) a large difference
in dielectric constant between the reactants and products is
necessary, so that product formation produces a change in the

4924 J. Phys. Chem. B, Vol. 108, No. 15, 2004
Abbott et al.
SCHEME 1. The Mechanism for Esterification between
Benzoic Acid and 1-Butanol
Figure 2. Ester conversion with time for a variety of pressures in
difluoromethane (HFC 32) at 363 K.
rest of this work, a reaction time of 2 h was used to ensure that
the system had reached equilibrium.
In a supercritical fluid, the pressure of the system affects the
activity of reactants and products; therefore, the equilibrium
constant should be expressed in terms of mole fraction instead
of concentration, giving
γCXCγDXD
K )
(1)
γAXAγBXB
and
γCγD
Kγ )
(2)
(3)
γAγB
Figure 3. Change in ln KX with pressure for the benzoic acid
esterification reaction at 363 K.
XCXD
XAXB
KX )
interactions will be negligible, because of the high polarizability
of the cybotactic region. At lower pressures, where the solvation
sheath may be incomplete, solute-solute interactions will
increase and the activity coefficients of the solutes will decrease.
By definition,16
where XA, XB, XC, and XD are the mole fractions of species A,
B, C, and D under equilibrium conditions, respectively. KX is
the apparent equilibrium constant, and γA, γB, γC, and γD are
the respective activity coefficients of species A, B, C, and D.
Unfortunately, there is negligible data on activity coefficients
in supercritical fluids; hence, only KX values can be discussed.
Figure 3 shows the variation of KX with pressure for the
esterification of benzoic acid with 1-butanol. KX increases as
the pressure decreases, in agreement with the results for
∆G ) ∆G° + RT ln x + RT ln γ
and it has been shown that17
(4)
∆G ) ∆G° + sπ*
(5)
esterification reactions by Ellington et al.8 and Hou et al.10
A
14-fold decrease in the apparent equilibrium constant is observed
when the pressure is increased from 70 bar to 220 bar. The
increase in the KX value with decreasing pressure signifies that
Kγ must be decreasing, because the equilibrium constant (K)
should be independent of pressure, because the process is
performed at constant volume.16 It can be argued that, at 220
bar, where the solvent-to-solute ratio is ca. 400, the solution
solute-solute interactions will be negligible and it can therefore
be assumed that Kγ ) 1 and KX ) K. Such an assumption could
be made for any system where the solutes have a relatively small
dipole moment. Making this assumption, values of Kγ can be
calculated as a function of pressure. At high pressures, the
solvation sheath around the solute will be full and solute-solute
where π* is the dipolarity/polarizability parameter from the
theory of Kamlet and Taft18 and s is a susceptibility constant.
Therefore, it is logical that the change in ln Kγ should be related
to π*. Figure 4 shows that the data from Figure 3 for the
esterification reaction correlates well with the π* data published
previously.14 This esterification reaction was also performed in
conventional liquid solvents for comparison. The apparent
equilibrium constant for this reaction in DCE at 363 K was
calculated to be 0.201, which is similar to the KX values in HFC
32 at moderate pressures (KX ) 0.23 at 125 bar), where local
composition enhancement is less important. The reaction was
also performed in cyclohexane (cHex), which has a much lower
dielectric constant than DCE or HFC 32 (for cHex, ꢀ ) 2.02 at

Equilibrium Reactions in sc HFC32
J. Phys. Chem. B, Vol. 108, No. 15, 2004 4925
Figure 4. Change in Kγ with solvent polarizability (π*) for the
esterification and aldol reactions.
Figure 5. Change in ln KX with pressure for the aldol condensation
reaction of cyclohexanone in HFC 32 at 363 K.
SCHEME 2. The Mechanism for the Acid-Catalyzed
Aldol Reaction of Cyclohexanone
themselves have a significant effect on the extent of a reaction
negating, to some degree, the effect of the solvent.
Aldol Condensation Reaction. In an aldol reaction, it is the
R-carbon of an aldehyde or ketone molecule that adds to the
carbonyl carbon of another molecule of the aldehyde or ketone.
Base-catalyzed aldol reactions are most common, but acid-
catalyzed reactions are known.19,20 Under acidic conditions, the
alcohol almost always undergoes acid-catalyzed dehydration to
yield the R,â-unsaturated ketone. Scheme 2 shows the mech-
anism of the acid-catalyzed reaction of the ketone, cyclohex-
anone (compound 1), which is used in this work.
Cyclohexanone was chosen because it is a liquid that readily
dissolves into solution, which allows the reaction to be followed
by dielectrometry, and p-Tos acid was once again used as the
acid catalyst. Analysis of the product showed that the dehydra-
tion product (compound 3 in Scheme 2), rather than the aldol
dimerization product (compound 2 in Scheme 2), was isolated.
Analogous to the esterification reaction, the dielectrometry
technique was observed to give a large change in dielectric
constant accompanying the formation of products. Initial experi-
ments followed conversion, as a function of time, and this
reaction was observed to reach equilibrium in <2 h.
273 K). However, the KX value was calculated to be 0.192,
which is very similar to that in DCE.
Figure 5 shows the apparent equilibrium constants for this
reaction as a function of pressure. The KX values shown in
Figure 5 follow the same trend that was observed with the
esterification reaction described previously, where KX increases
as pressure decreases. A sharp increase in KX can be seen as
the pressure decreases toward the critical pressure pc. The
arguments applied to the esterification reaction also apply to
the results observed here for the aldol reaction, where the
increased value of KX at low pressures is thought to be due to
local composition enhancements.
The change in apparent equilibrium constant with pressure
for the aldol reaction is less than that observed for the
esterification reaction, showing only a 4-fold increase when
decreasing the pressure from 200 bar to 70 bar (cf. the 14-fold
change previously discussed). At higher pressures, note that both
the esterification and aldol reactions have similar KX values;
therefore, the main factor in causing only a 4-fold change in
rate is due to the much lower KX values observed for the aldol
reaction at low pressures. Using the same assumption about the
ideality of the solution as discussed previously, Figure 4 shows
the change in ln Kγ with π* for the aldol reaction, and, again,
a linear relationship is observed. The decrease in Kγ with π* is
To assess whether the dielectric constant of the solution has
this effect in a supercritical fluid, the esterification reaction was
performed in sc CO2 at 363 K (for CO2, ꢀ ) 1.2 at 363 K and
200 bar). Results obtained for KX are shown in Figure 3, and it
can be seen that the KX values are similar to those for HFC 32.
This is a remarkable observation, considering the vast differ-
ences in dielectric constant between the two solvents. In the
low-dielectric media such as cHex and sc CO2, it is surprising
that the reaction progresses at all, because the dissociation of
the acid catalyst should be negligible. This suggests that either
the catalyst activity is not a factor that affects the reaction rate
or the reagents affect the dielectric properties of the solution
sufficiently to allow dissociation of the acid. The starting
dielectric constant of the solution containing all the reagents in
CO2 was 5.0, which is much higher than the dielectric constant
for the pure solvent (ꢀ < 2), and significantly, it is not much
lower than the value measured for the solution in HFC32, which
was 5.48 (at 90 °C and 170 bar), showing that the latter
explanation is the cause of the apparent anomalous behavior.
Thus, although the reagents are present in a small concentration
(1 mol %), they have a marked effect on the dielectric constant
of the solution. Hence, it can be seen that the reagents

4926 J. Phys. Chem. B, Vol. 108, No. 15, 2004
Abbott et al.
less pronounced than that for the esterification reaction. The
dipole moment of cyclohexanone (µ ) 2.97 D)21 is larger than
that for the aldol product (µ ) 2.75 D) or water (µ ) 1.86 D).
Because
technique can be applied, it is a quick and simple method.
Equilibrium constants were calculated for both reactions, as a
function of pressure, and the apparent equilibrium constants
decreased as the pressure increased. The enhanced equilibrium
constants observed at low pressure were thought to be due to
local composition enhancements. The lower observed apparent
equilibrium constants for the aldol reaction, compared to those
for the esterification reaction, are explained in terms of dipolar
interactions.
γ
aldolγwater
Kγ )
(6)
2
(γketone
)
then the dipole-dipole interactions will increase and the activity
coefficients for all of the species will decrease as the polariz-
ability of the supercritical solution decreases. The same is true
for the previously mentioned esterification reaction; however,
in this case, the dipole moments of the reagents (µ ) 1.70 D
for butanol and µ ) 2.40 D for benzoic acid) are similar to
those of the products (µ ) 2.19 D for butyl benzoate). Defining
a dipole moment ratio for the reaction (Kµ) as
Acknowledgment. The authors would like to thank Ineos
Fluor, The Royal Society, and EPSRC (under GR/M67209) for
financial support.
References and Notes
(1) Jessop, P. G.; Leitner, W. Chemical Synthesis Using Supercritical
Fluids; Wiley-VCH: Weinheim, Germany, 1999.
(2) Kimura, Y.; Yoshimura, Y.; Nakahara, M. J. Chem. Phys. 1989,
90, 5679.
(3) Kimura, Y.; Yoshimura, Y. J. Chem. Phys. 1992, 96, 3085.
(4) Kimura, Y.; Yoshimura, Y. J. Chem. Phys. 1992, 96, 3824.
(5) Gupta, R. B.; Combes, J. R.; Johnston, K. P. J. Phys. Chem. 1993,
97, 707.
(6) O’Shea, K.; Kirmse, K. M.; Fox, M. A.; Johnston, K. P. J. Phys.
Chem. 1991, 95, 7863.
(7) Mikami, K.; Matsukawa, S.; Kayaki, Y.; Ikariya, T. Tetrahedron
Lett. 2000, 41, 1931.
(8) Ellington, J. B.; Park, K. M.; Brennecke, J. F. Ind. Eng. Chem.
Res. 1994, 33, 965.
(9) Ellington, J. B.; Brennecke, J. F. J. Chem. Soc., Chem. Commun.
1993, 1094.
(10) Hou, Z.; Han, B.; Zhang, X.; Zhang, H.; Liu, Z. J. Phys. Chem. B
2001, 105, 4510.
(11) Abbott, A. P.; Eardley, C. A.; Tooth, R. J. J. Chem. Eng. Data
1999, 44, 112.
µ
aldolµwater
Kµ )
(7)
2
(µketone
)
a value of 1.00 is obtained for the esterification reaction whereas
the value for the aldol reaction is 0.58. To account for the trends
observed in Figure 4, the decrease in the denominator in eq 7
with solvent polarizability must be proportionately larger than
that for the corresponding expression for the esterification
reaction (hence, Kγ does not decrease to the same extent with
the more-polar reagents). In the absence of any activity
coefficient data, this is difficult to quantify; however, interest-
ingly, the ratio of the Kµ values for the two reactions (0.58) is
very similar to the ratio of the two slopes in Figure 4 (0.52),
showing that the change in apparent equilibrium constant with
pressure is dependent on the dipolar properties of the reagents.
Hence, solute dipolar interactions seem to affect the position
of equilibrium, and this observation is consistent with the
assumptions made previously8,10 for similar reactions in super-
critical solutions.
(12) Abbott, A. P.; Eardley, C. A. J. Phys. Chem. B 1998, 102, 8574.
(13) Abbott, A. P.; Eardley, C. A. J. Phys. Chem. B 1999, 103, 2504.
(14) Abbott, A. P.; Corr, S.; Durling, N. E.; Hope, E. G. J. Phys. Chem.
B 2003, 107, 10628.
(15) Abbott, A. P.; Corr, S.; Durling, N. E.; Hope, E. G. J. Chem. Eng.
Data 2002, 47, 900.
(16) Atkins, P.; de Paula, J. Physical Chemistry, 7th ed.; Oxford
University Press: New York, 2002.
(17) Taft, R. W.; Abraham, M. H.; Doherty, R. M.; Kamlet, M. J. J.
Am. Chem. Soc. 1985, 107, 3105.
(18) Kamlet, M. J.; Abboud, J.-L. M.; Taft, R. W. J. Am. Chem. Soc.
1977, 99, 6027.
(19) Mahrwald, R.; Gundogan, B. J. Am. Chem. Soc. 1998, 120, 413.
(20) Simth, M. B.; March J. March’s AdVanced Organic Chemistry, 5th
ed.; Wiley: New York, 2001.
Conclusions
The first examples of an esterification and aldol condensation
reaction in supercritical difluoromethane (sc HFC 32) are
presented here. Using these reactions as examples, the successful
application of the in situ dielectrometry technique to follow
equilibrium reactions was demonstrated. The advantages and
disadvantages of applying this technique to follow reactions
were discussed; however, it could be seen that when this
(21) Dipole moments calculated using a molecular modeling package
(Spartan Pro, Wave Function, Inc., Irvine, CA).