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Ind. Eng. Chem. Res. 1998, 37, 3252-3259
Phase-Transfer Catalysis in Supercritical Carbon Dioxide: Kinetic and Mechanistic Investigations of Cyanide Displacement on Benzyl Chloride Karen Chandler, Christy W. Culp, David R. Lamb, Charles L. Liotta, and Charles A. Eckert* Schools of Chemical Engineering and Chemistry and Specialty Separations Center, Georgia Institute of Technology, Atlanta, Georgia 30332-0100
This work reports the first studies designed to examine the detailed mechanism of a phasetransfer catalyzed reaction between a supercritical CO2 phase and a solid salt phase. The nucleophilic displacement of benzyl chloride with potassium cyanide to form phenylacetonitrile and potassium chloride was carried out with a tetraheptylammonium salt as the phase-transfer catalyst. The effects of various reaction variables on the kinetics were investigated, including the amount of catalyst, the amount of potassium cyanide, the presence of acetone cosolvent, and temperature. The kinetic data, along with catalyst solubility measurements, indicate that the operating reaction mechanism is a three-phase system consisting of a supercritical CO2 phase, a catalyst-rich phase, and a solid salt phase and that the reaction actually occurs in the catalystrich phase. Further, the reaction mechanism was investigated with two additional phase-transfer catalysts, 18-crown-6 and poly(ethylene glycol), and these results are consistent with the postulated three-phase mechanism. Introduction Phase-transfer catalysis (PTC) is a powerful and widely used technique for conducting heterogeneous reactions between two or more reactants in two or more immiscible phases (Dehmlow, 1977; Weber and Gokel, 1977; Starks and Liotta, 1978; Freedman, 1986; Dehmlow and Dehmlow, 1993; Starks et al., 1994). Traditionally, polar aprotic solvents have been used to dissolve the reactants into a single phase where reactions may be carried out homogeneously. However, these solvents are frequently expensive, environmentally undesirable, and difficult to remove from the reaction products. PTC eliminates the need for these homogeneous solvents by employing a phase-transfer catalyst to transfer one of the reacting species from one phase into a second phase where reaction can occur. Generally, PTC involves the transfer of an ionic reactant from an aqueous or solid phase into an organic phase across an interfacial area, where it reacts with a nontransferred reactant. Once the reaction is complete, the catalyst must transport the ionic product back to the aqueous or solid phase to start a new catalytic cycle (Weber and Gokel, 1977; Starks et al., 1994). The classical description of the PTC cycle between an aqueous or solid phase and an organic phase is illustrated in Figure 1. Typically, polar organic solvents, such as methylene chloride, are used in PTC to obtain a high rate of ion transfer and to increase reaction rates. However, PTC has also been proven to be efficient with less polar and more environmentally acceptable solvents such as toluene, hexane, and heptane (Starks et al., 1994). Consequently, it is feasible that even nonpolar supercritical fluids (SCFs), such as CO2, might be acceptable solvents for many PTC reactions. * E-mail:
[email protected]. Phone: (404) 894-7070. Fax: (404) 894-9085.
Figure 1. PTC cycle between an aqueous or solid phase and an organic phase (Starks, 1997).
SCF solvents have an unusual combination of physical properties, making them attractive solvents for many reactions (McHugh and Krukonis, 1994; Savage et al., 1995; Eckert et al., 1996). The most widely used SCF, CO2, is inexpensive, nonflammable, and environmentally benign (Hyatt, 1984; Eckert et al., 1986). Also, since supercritical CO2 is highly compressible in the near-critical region, small changes in temperature and pressure result in large density changes and considerable solubility variations. Therefore, supercritical CO2 is easily separated from reaction products by depressurization (Subramaniam and McHugh, 1986; Kim and Johnston, 1987; Brennecke and Eckert, 1989; Eckert and Knutson, 1993). SCF solvents have solute molecular diffusivities much higher than those of liquids and viscosities 2 orders of magnitude lower than liquids (van Wasen et al., 1980; Brennecke and Eckert, 1989), both of which should make SCF solvents attractive for PTC reactions that are typically mass transfer limited in liquid solvents (Wang and Wu, 1991; Wang and Yang, 1992). Additionally, the critical properties of CO2 are very accessible (Tc ) 31 °C and Pc ) 74 bar), and supercritical CO2 can be used as the reaction solvent even when thermally labile reactants and catalysts are required (McHugh and Krukonis, 1994). The first reported example of a PTC reaction carried out in supercritical CO2 was the nucleophilic displace-
S0888-5885(97)00741-0 CCC: $15.00 © 1998 American Chemical Society Published on Web 06/27/1998
Ind. Eng. Chem. Res., Vol. 37, No. 8, 1998 3253
Figure 2. Nucleophilic displacement reaction of benzyl chloride with potassium cyanide.
ment of benzyl chloride with bromide ion in the presence of two phase-transfer catalysts, tetraheptylammonium bromide and 18-crown-6 (Dillow et al., 1996). In the current investigation, the nucleophilic displacement reaction of benzyl chloride with potassium cyanide to form phenylacetonitrile and potassium chloride is reported (Figure 2). Cyanide displacement on benzyl chloride was chosen as the model irreversible SN2 reaction studied in supercritical CO2 because of its simplicity. Also, cyanide displacement reactions on benzyl halides have been reported previously in traditional liquid solvents by several investigators (Cook et al., 1974; Zubrick et al., 1975; Reeves and White, 1976; Liotta et al., 1987, 1997). The reaction studied here is of great practical interest because the product, phenylacetonitrile, is an important starting material for various industrially important syntheses, including extensive use in the preparation of a variety of pharmaceuticals (Starks et al., 1994). PTC Mechanisms Most PTC reactions reported in the literature involve an aqueous liquid phase and an organic liquid phase (liquid-liquid PTC) or a solid phase and an organic liquid phase (solid-liquid PTC). In their most basic forms, the mechanisms of both cases are represented by Figure 1. Selecting a phase-transfer catalyst is often challenging for both types of reactions, and many different catalyst features must be considered, including activity, stability, availability, cost, toxicity, recovery, and disposal (Starks et al., 1994). In liquid-liquid PTC, some of the most commonly used catalysts are quaternary ammonium salts (Starks, 1971; Starks and Owens, 1973; Solaro et al., 1980; Ragaini et al., 1988; Wang and Wu, 1991; Makosza, 1997). Generally, they are easily separated from reaction products and reasonably inexpensive but may undergo decomposition by internal displacement at high temperatures and by Hofmann degradation in the presence of strong bases. Furthermore, the size of a quaternary salt is important. If the quaternary cation is small, the salt is relatively hydrophilic and will partition mainly into the aqueous phase, but salts with larger organic chains are more lipophilic and will partition into the organic phase where reaction occurs (Gibson and Weatherburn, 1972; Brandstrom, 1977; Starks et al., 1994). Solid-liquid PTC was developed to overcome the problem of water of hydration that sometimes accompanies the catalyst from the aqueous to the organic phase in liquid-liquid PTC. Quaternary ammonium salts are usually effective for solid-liquid PTC as well as liquid-liquid PTC (Dehmlow, 1977; Fair, 1985; Pradhan and Sharma, 1990; Dehmlow and Dehmlow, 1993; Starks et al., 1994). Also, nonionic catalysts, such as crown ethers and poly(ethylene glycol) (PEG), have been proven effective for many solid-liquid PTC reactions (Cook et al., 1974; Liotta and Harris, 1974; Liotta et al., 1974, 1987, 1997; Childs and Weber, 1976; Dehmlow, 1977). Crown ethers and PEG complex with salts such that both the cations and anions are trans-
ferred to the organic phase, where the anions are activated for reaction. In both liquid-liquid and solid-liquid PTC, a threephase PTC system can occur if the phase-transfer catalyst has limited solubility in both phases. The reaction often occurs in the catalyst-rich third phase, but examples also exist where reaction still occurs in the organic phase. Several examples of three-phase liquid-liquid PTC behavior have been described using both insoluble liquid catalysts and catalysts bound to insoluble supports (Regen, 1976; Neumann and Sasson, 1984; Mason et al., 1990; Dutta et al., 1997; Ohtani et al., 1997). In solid-liquid PTC, the formation of a third phase on the solid salt is typically caused by the presence of water in the system, and the third phase has been termed the omega phase (Liotta et al., 1987, 1997; Pradhan and Sharma, 1990). Three-phase PTC reactions often have advantages over conventional twophase PTC reactions, such as accelerated rates and simplified catalyst recovery (Wang and Weng, 1988; Mason et al., 1991; Starks et al., 1994). In this investigation, reaction kinetics and catalyst solubility data were studied in order to gain an understanding of the important mechanistic features involved in solid-SCF PTC. The nucleophilic displacement reaction between a solid salt, potassium cyanide, and an organic reactant, benzyl chloride, was investigated in supercritical CO2 using a tetraheptylammonium salt as a catalyst. Replacement of the usual organic liquid phase by CO2 results in a significant decrease in catalyst solubility, because the dielectric constant and cohesive energy density of CO2 are considerably less than those of even nonpolar organic solvents. Therefore, it is increasingly likely that a three-phase system could form, with the reaction occurring in the catalyst-rich phase. In many SCF applications, small amounts of polar cosolvents are used to modify the solvent properties of supercritical CO2. Cosolvents are known to have very high local concentrations in the vicinity of the solute molecules. Consequently, the addition of cosolvents can enhance solute solubilities and reaction rates and selectivities (Dobbs et al., 1987; Eckert et al., 1993; Eckert and Knutson, 1993; Ekart et al., 1993; Van Alsten and Eckert, 1993; Dillow et al., 1997). Because the potential to tailor SCFs for reactions is increased by the addition of cosolvents, it might be desirable to use cosolvents for industrial PTC reactions using SCF solvents. Therefore, reaction kinetics were measured both with and without the addition of a cosolvent, acetone, to determine the influence of organic cosolvents on solid-SCF PTC reactions. Experimental Methods Materials. SFC Grade carbon dioxide (99.99%) was obtained from Matheson Gas Products. Trace amounts of water in the carbon dioxide were removed using a gas purifier (Model 450B) with a filter cartridge (Type 451), also obtained from Matheson. The reactants, benzyl chloride (99%) and potassium cyanide (97%, ACS Reagent), and the reaction product, phenylacetonitrile (99+%), were obtained from Aldrich Chemical Co. and were used without further purification. The phasetransfer catalyst, tetraheptylammonium chloride (98%), and the calibration standard, p-toluic acid (98%), were also obtained from Aldrich. HPLC Grade acetone (99.9+%) was used as a cosolvent in several reactions, and trace amounts of water in the acetone were removed
3254 Ind. Eng. Chem. Res., Vol. 37, No. 8, 1998
Figure 3. Schematic of the PTC reaction apparatus.
using molecular sieves (4A, 1.6 mm pellets). Both the acetone and molecular sieves were obtained from Aldrich. Apparatus. Figure 3 shows a schematic of the PTC reaction apparatus. The reactor was a stainless steel, batch reactor (Parr Instrument Co., Model 4561) with a maximum working pressure of 208 bar and a maximum working temperature of 350 °C. Stirring was provided by a magnetic drive (Parr, Model A1120HC) equipped with a paddle-type impeller, and stainless steel balls were added to the reactor to increase agitation. The seal between the stirrer and the reactor was made with a silver gasket, and the seal between the reactor body and the reactor head was made with a flat Teflon gasket held in a confined recess in the reactor head. The internal volume of the reactor, with the stirrer and stainless steel balls, was determined to be approximately 285 mL by filling the reactor with pure CO2 at constant temperature and pressure and using a wet test meter to measure the volume of CO2 in the reactor. A three-mode temperature controller and tachometer (Parr, Model 4842) were used to control the temperature of the reactor to (1 °C and the stirring speed to (5 rpm. The temperature inside the reactor was monitored with a type J thermocouple, and heat was provided by a hightemperature heating mantle housed in an aluminum shell. A digital pressure transducer (Heise, Model 901B) was used to monitor constantly the reactor pressure, and a safety rupture disk, made of Inconel, was used to ensure the pressure in the reactor remained below the reactor pressure rating. The Parr reactor was modified by replacing all of the standard valves and fittings with low-volume HiP valves and fittings to decrease the reactor dead volume. The CO2 was supplied by a high-pressure syringe pump (Isco, Inc., Model 500D) through stainless steel tubing (3.18 mm o.d. and 1.52 mm i.d.) to one inlet port on the reactor head. The benzyl chloride was delivered to the reactor through a second inlet port using a pressure generator (High Pressure Equipment Co, Model 87-65) and stainless steel tubing (1.59 mm o.d. and 0.762 mm i.d.). A third port was used as the outlet for sampling. Small internal diameter tubing (1.59 mm o.d. and 0.127 mm i.d.) extending approximately 3 cm into the reactor was used as the sample-withdrawal line. A two-position valve (Valco Instruments Co. Inc.) and a 250 µL sample loop were used to collect the samples. Experimental Procedure. Because small amounts of water have been shown to have extreme effects on reaction kinetics for solid-liquid PTC reactions, efforts
were made to ensure that no water was present during the reactions in this investigation (Liotta et al., 1987, 1997; Pradhan and Sharma, 1990; Starks et al., 1994). Before the reactor was loaded for each run, it was dried in a vacuum oven overnight to remove any water that was adsorbed on the reactor walls. The reactor was then sealed and pressurized with CO2 to approximately 70 bar at 100 °C. All of the lines were flushed with CO2 several times to ensure that all of the water was removed from the tubing. After cooling and depressurization, the reactor was loaded in a drybox under a nitrogen (Air Products and Chemicals, Inc.) atmosphere. The solid reactant, potassium cyanide, was ground to a fine powder in the reactor. The catalyst, tetraheptylammonium chloride, was also added in the drybox, as was the acetone for the reactions carried out with a cosolvent. The reactor was removed from the drybox, and the nitrogen atmosphere in the reactor was replaced with gaseous CO2. To achieve reproducible kinetic data, the reactor contents were stirred (200 rpm) for approximately 16 h at 35 °C and atmospheric pressure. In addition to obtaining a constant salt particle size, this step allowed the reversible ion exchange reaction between the catalyst, tetraheptylammonium chloride, and the potassium cyanide to reach equilibrium (Liotta et al., 1987; Esikova and Yufit, 1990). This was particularly important for this reaction, because the actual catalyst for the displacement reaction was tetraheptylammonium cyanide, which is not commercially available and must be produced in situ. At the beginning of each run, the temperature was raised to the desired reaction temperature (50 or 75 °C) and the system was pressurized to 138 bar with CO2. Once the reaction conditions were stable, the second reactant, benzyl chloride, was introduced at the reaction pressure using a high-pressure syringe pump. At a given reaction time, three samples were removed from the system. For each sample, the sample loop was flushed with approximately two volumes of reaction fluid to ensure that representative samples were obtained. The total pressure drop for each set of samples (three samples plus venting) was less than 0.5 bar. No more than six sets of samples were removed from the reaction system for any given run, and the pressure was controlled at 138 ( 2 bar. Sample Analysis. Each sample was depressurized into 3 mL of cold acetone, and the sample loop was rinsed with an additional 2 mL of acetone. The acetone contained a known amount of calibration standard, p-toluic acid. The amounts of benzyl chloride and phenylacetonitrile in each sample were determined using a gas chromatograph (GC) (Varian Associates, Model 3400) equipped with a flame ionization detector (FID). A 15 m × 0.53 mm DB-17 column with a 1.0 µm film thickness (J & W Scientific Inc.) was used to achieve component separation. Previously prepared calibration curves were used to determine the concentrations of both benzyl chloride and phenylacetonitrile from the resulting GC peak areas. Results and Discussion Effect of Catalyst Amount. The nucleophilic displacement reaction of benzyl chloride with potassium cyanide was carried out at 75 °C and 138 bar. The initial concentration of benzyl chloride was 0.055 mol/ L, and a five times excess (0.078 mol) of potassium
Ind. Eng. Chem. Res., Vol. 37, No. 8, 1998 3255
cyanide was used in each run. Also, a 5 mol % concentration of acetone was added as a cosolvent. Four catalyst amounts were investigated including 8.8 × 10-6, 1.6 × 10-4, 4.0 × 10-4, and 1.6 × 10-3 mol. The catalyst amounts ranged from 0.06 to 10% of the concentration of the limiting reactant, benzyl chloride. The phase behavior of CO2 and benzyl chloride at the reaction conditions was estimated using the PengRobinson equation of state (EOS), where the critical properties of benzyl chloride were calculated using the Joback method (Reid et al., 1987). On the basis of the resulting vapor-liquid equilibrium curve, the concentration of benzyl chloride used in this investigation was in the one-phase region at the reaction conditions. The addition of acetone would alter the vapor-liquid equilibrium curve, but the solubility of the benzyl chloride would increase. Therefore, at the experimental conditions with the addition of 5 mol % acetone, the initial concentration of benzyl chloride would still be in the one-phase region. The 5 mol % acetone that was added in each run was based on the density of pure CO2, which was calculated using an EOS developed by Ely et al. (1989). The CO2/acetone mixture densities were calculated using the Peng-Robinson EOS with one interaction parameter regressed from the experimental data of Tilly et al. (1994). PTC reactions require both a transfer step and an intrinsic reaction step, and depending on the reaction conditions, either step can be rate limiting. The nucleophilic displacement reaction between a solid salt and benzyl chloride in supercritical CO2 no longer depends on stirring speed above 100 rpm for this system (Dillow et al., 1996), which indicates that the reaction is kinetically controlled. All of the reactions reported in this investigation were carried out with a stirring rate of 200 rpm to ensure that the reaction was not mass transfer limited. Assuming the reaction step is rate limiting, the rate expression for the nucleophilic displacement reaction is given by
d[R - X] ) k[Q+Y-][R - X] dt
(1)
where t is the reaction time and k is the rate constant. Pseudo-first-order kinetics have been determined repeatedly for numerous liquid-liquid, solid-liquid, and even three-phase PTC reactions. However, firstorder behavior can be expected only if an excess of Yis present, which makes the concentration of Q+Yeffectively constant in the reacting phase. For this case, eq 1 reduces to
d[R - X] ) k1[R - X] dt
(2)
where k1 is the pseudo-first-order rate constant. The assumptions made in deriving eq 2 are consistent with the reaction conditions used in this investigation. The stirring rate was twice that needed to eliminate mass-transfer limitations, and a large excess of potassium cyanide was present in the reaction system. The first-order, irreversible rate expression that was used to determine rate constants is given by
k1t ) ln(CA0/CA)
(3)
where CA0 is the initial concentration of the limiting
Figure 4. Effect of the catalyst amount on the conversion of benzyl chloride at 75 °C and 138 bar with 5 mol % acetone: (() no catalyst; (1) 8.8 × 10-6 mol of catalyst; (2) 1.6 × 10-4 mol of catalyst; (b) 4.0 × 10-4 mol of catalyst; (9) 1.6 × 10-3 mol of catalyst.
Figure 5. Evidence of irreversibility and pseudo-first-order kinetics at 75 °C and 138 bar with 5 mol % acetone: (1) 8.8 × 10-6 mol of catalyst; (2) 1.6 × 10-4 mol of catalyst; (b) 4.0 × 10-4 mol of catalyst; (9) 1.6 × 10-3 mol of catalyst.
reactant, benzyl chloride, and CA is the concentration of benzyl chloride at time t. The conversion of benzyl chloride as a function of time is presented in Figure 4 for the four different amounts of catalyst studied in this investigation. Also, the reaction was carried out under identical reaction conditions without catalyst, and these data are also presented in Figure 4. The error bars shown in Figure 4, as well as all of the other figures, represent the 95% confidence intervals of the average of three samples. In the absence of catalyst, the reaction proceeded for 48 h with a conversion of only 5%. On the other hand, the run with the highest amount of catalyst (1.6 × 10-3 mol) went to completion (100% phenylacetonitrile) in less than 10 h. These results demonstrate the activity of the phase-transfer catalyst. Evidence of irreversibility and pseudo-first-order kinetics is shown in Figure 5, where the graph of ln(CA0/CA) versus time for all of the catalyst amounts produces straight lines, justifying the use of eq 3 to calculate pseudo-first-order rate constants. The pseudo-first-order rate constants for each of the four catalyst amounts are presented in Table 1; the data are an average of at least three runs and are reported with standard deviations.
3256 Ind. Eng. Chem. Res., Vol. 37, No. 8, 1998 Table 1. Pseudo-First-Order Rate Constants for the Reaction of Benzyl Chloride with Potassium Cyanide as a Function of Catalyst Amounta catalyst amount (mol) 10-6
8.8 × 1.6 × 10-4 4.0 × 10-4 1.6 × 10-3
catalyst % of initial benzyl chloride (mol %)
k1 × 106 (s-1)
0.06 1.0 2.5 10
0.44 ( 0.07 9.7 ( 0.9 42 ( 3 155 ( 3
a Reaction conditions: temperature, 75 °C; pressure, 138 bar; cosolvent, 5 mol % acetone; density, 13.5 mol/L; stirring speed, 200 rpm; 0.055 mol/L benzyl chloride; 0.078 mol potassium cyanide.
Figure 7. Three-phase PTC system with a catalyst-rich surface phase under dynamic conditions.
Figure 6. Effect of the catalyst amount on the pseudo-first-order rate constant at 75 °C and 138 bar with 5 mol % acetone.
The lowest catalyst amount reported in Table 1 (8.8 × 10-6 mol) is the estimated solubility of the catalyst in supercritical CO2 with 5 mol % acetone cosolvent at 75 °C and 138 bar. This solubility measurement was made for tetraheptylammonium bromide using a continuous flow apparatus (Dillow et al., 1996). In this investigation, the catalyst was tetraheptylammonium cyanide, which was formed in situ by the ion exchange between tetraheptylammonium chloride and potassium cyanide. Because tetraheptylammonium cyanide was not available commercially, solubility measurements on this specific catalyst were not possible. However, the ease of transfer of bromide and cyanide ions is very similar in organic solvents, and therefore, the solubilities of the two catalysts were assumed to be approximately similar (Starks et al., 1994). As shown in Table 1, the rate constant continuously increased as the amount of catalyst was increased. Furthermore, a graph of the pseudo-first-order rate constant versus the amount of catalyst (Figure 6) suggests that the rate of reaction was linearly dependent on the amount of catalyst even at 2 orders of magnitude above the estimated solubility of the catalyst. The low catalyst solubility in the supercritical CO2 phase and the linear increase in rate constant 2 orders of magnitude above the estimated solubility limit indicate that the reaction mechanism involved the formation of a catalyst-rich third phase in which the reaction actually occurred. A simplified representation of the hypothesized three-phase system under dynamic reaction conditions is shown in Figure 7. Small particles of the solid phase were surrounded by the catalyst phase, and the organic compounds, benzyl chloride and phenylacetonitrile, partitioned between the CO2 phase and the catalyst-rich phase. Even though no water was
present in the reaction system, the catalyst-rich phase on the salt surface could still be considered an omega phase. Catalyst Solubility. The hypothesis that the cyanide displacement on benzyl chloride occurred in a catalyst-rich phase on the surface of the solid phase is dependent on the assumption that the solubility of tetraheptylammonium cyanide is of the same order of magnitude as the solubility of tetraheptylammonium bromide in supercritical CO2. To verify this assumption, two additional experiments were performed. In the first experiment, Fourier transform infrared (FT-IR) spectroscopy was used to measure the IR spectrum of a supercritical CO2 phase in contact with solid potassium cyanide and tetraheptylammonium chloride. The potassium cyanide and the tetraheptylammonium chloride were premixed, and a high-pressure IR cell was loaded with a large excess of the mixture. The cell was pressurized with CO2 and brought to standard reaction conditions. The catalyst has a very large number of C-H bonds, and therefore, the C-H vibrational modes should be evident in the IR region even at very low catalyst concentrations, such as the measured solubility of tetraheptylammonium bromide. IR spectra of the CO2 phase were taken over several hours, but the C-H vibrational modes of the catalyst were not observed, indicating that the solubility of tetraheptylammonium cyanide is no higher than the measured solubility of tetraheptylammonium bromide. Quaternary ammonium salts readily undergo decomposition at temperatures as low as 100 °C. Therefore, when solutions of tetraheptylammonium chloride in acetone were injected into a GC coupled with a mass spectrometer (MS), the catalyst decomposed in the injector (275 °C) and the decomposition products were identified. In the second experiment, samples from a kinetic run with 4.0 × 10-4 mol of catalyst were analyzed using the GC-MS. The samples were collected from the supercritical CO2 phase, and a filter was present just before the sample line to ensure no entrainment of the solid phase occurred during sampling. Therefore, the catalyst would be in the samples only if it were solubilized in the supercritical CO2 phase. Although the decomposition product, N,N-diheptyl-1heptanamine, is detectable by the GC-MS 1 order of magnitude below the catalyst concentration in the reaction system, it was not detected in the actual samples. This further indicates that the catalyst was
Ind. Eng. Chem. Res., Vol. 37, No. 8, 1998 3257 Table 2. Pseudo-First-Order Rate Constants for the Reaction of Benzyl Chloride with Potassium Cyanide Using a Catalyst Amount of 4.0 × 10-4 mol (2.5 mol % of the Initial Benzyl Chloride)a temp (°C)
potassium cyanide amount (mol)
acetone cosolvent (mol %)
density (mol/L)
k1 × 106 (s-1)
75 75 75 50 50
0.078 0.039 0.078 0.078 0.078
5 5 none 5 none
13.5 13.5 9.22 16.5 15.2
42 ( 3 39 ( 1 72 ( 7 0.81 ( 0.09 1.3 ( 0.1
a Reaction conditions: pressure, 138 bar; stirring speed, 200 rpm; 0.055 mol/L benzyl chloride.
not soluble in the CO2 phase at the amounts present in the reactions. Effect of Potassium Cyanide Amount. The reaction was carried out under identical conditions with 4.0 × 10-4 mol of catalyst (2.5% of the benzyl chloride concentration) and half the amount of potassium cyanide (0.039 mol) used in the first set of reactions. The pseudo-first-order rate constants for this reaction and the reaction with the same amount of catalyst and 0.078 mol of potassium cyanide are reported in Table 2. Examination of the dependence of the pseudo-first-order rate constant on the amount of potassium cyanide in the reaction system revealed that decreasing the amount of the salt by half produced no significant changes in the rate of reaction. This result might seem inconsistent with typical surface phase reactions. However, estimates of the surface area of the solid phase indicated that, even at half the initial potassium cyanide amount, the catalyst was the limiting reagent. Therefore, an increase in the amount of potassium cyanide would not increase the number of sites for reaction. This conclusion is also supported by the first set of reactions, where an increase in the amount of catalyst above 4.0 × 10-4 mol increased the rate of reaction, again indicating that the catalyst was the limiting amount. Effect of Cosolvent. The nucleophilic displacement reaction of benzyl chloride with potassium cyanide was carried out at two temperatures, 50 and 75 °C, and at a pressure of 138 bar, both with and without acetone. The conversion of benzyl chloride as a function of time for the reactions with and without cosolvent is presented in Figure 8, and the pseudo-first-order rate constants are reported in Table 2. The reactions were carried out again with 4.0 × 10-4 mol of catalyst and 0.078 mol of potassium cyanide. At both temperatures, the rate of reaction increased when no acetone was present in the reaction system. Again, this result is consistent with the premise that a three-phase system formed and reaction occurred in the catalyst-rich third phase. On the basis of all of the presented kinetic data, it is postulated that the catalyst-rich third phase formed on the solid surface, as depicted in Figure 9. The long alkyl groups attached to the quaternary cations greatly enhanced the organic character of the solid surface. Therefore, the organic reactant, benzyl chloride, could partition between the supercritical CO2 phase and the catalyst phase. Undoubtedly, the addition of acetone affected the organic character of both phases. However, because polar cosolvents have very high local concentrations in the vicinity of solute molecules in supercritical CO2, it is likely that the addition of acetone affected the organic character of the CO2 phase more than it affected the organic character of the long alkyl groups of the
Figure 8. Effect of the presence of acetone and temperature on the conversion of benzyl chloride using 4.0 × 10-4 mol of catalyst at 138 bar: (b) 75 °C with 5 mol % acetone; (O) 75 °C with no acetone; (9) 50 °C with 5 mol % acetone; (0) 50 °C with no acetone.
Figure 9. Three-phase PTC system with a catalyst-rich third phase that greatly enhances the organic character of the solid salt surface.
catalyst. Consequently, the addition of acetone changed the distribution coefficient of benzyl chloride between the supercritical CO2 phase and the catalyst phase and therefore decreased the rate of reaction. Effect of Temperature. The effect of temperature on the conversion of benzyl chloride is also depicted in Figure 8. The activation energies with and without acetone are the same within the limits of experimental error, 35 ( 2 and 36 ( 2 kcal/mol, respectively. The activation energies are quite large for a catalytic process, but PTC is not a typical catalytic process where the catalyst provides an alternative pathway with a lower activation energy. In PTC, the phase-transfer catalyst is used primarily to bring the reactants together. Nevertheless, activation energies for most kinetically controlled PTC reactions typically range from 10 to 25 kcal/mol (Solaro et al., 1980; Balakrishnan and Ford, 1983; Wang and Weng, 1988; Pradhan and Sharma, 1990). However, the temperature dependence of PTC reactions is very complicated, particularly for three-phase systems where small temperature changes often result in large changes in the composition of each phase. One example of unusual temperature sensitivity was reported for a three-liquid-phase PTC system, where an activation energy as high as 57 kcal/mol was attributed to the destabilization of the third phase and precipitation of the catalyst (Mason et al., 1991). Conversion with Different Catalysts. The nucleophilic displacement reaction of benzyl chloride with potassium cyanide was carried out at 75 °C and 138 bar
3258 Ind. Eng. Chem. Res., Vol. 37, No. 8, 1998
occurring in a catalyst-rich phase could provide several important advantages over conventional two-phase systems. Supercritical CO2 could be used as the reaction solvent with traditional PTC catalysts, despite low solubility in the CO2 phase. Therefore, organic cosolvents would not be required to increase the solubilities of the catalysts. Furthermore, catalyst removal and recovery procedures are often simplified in three-phase PTC systems. Acknowledgment We greatly appreciate the financial support of the Environmental Protection Agency (Grant No. 822730) and E. I. DuPont de Nemours. We also thank Dr. Barry L. West, Dr. Sergei G. Kazarian, and Dr. David M. Bush for their help and advice. Figure 10. Conversion of benzyl chloride using three-phasetransfer catalysts (4.0 × 10-4 mol) at 75 °C and 138 bar in the absence of acetone: (O) tetraheptylammonium cyanide; (4) 18crown-6; (0) PEG.
in the presence of two nonionic catalysts, 18-crown-6 and PEG. The same amount of catalyst, 4.0 × 10-4 mol, was used in each reaction, and the reactions were run in the absence of cosolvent. Under these reaction conditions, neither catalyst was soluble in the supercritical CO2 phase. Previously, solubility measurements showed pure 18-crown-6 to be highly soluble in supercritical CO2 but essentially insoluble when complexed with potassium bromide, even with 5 mol % acetone (Dillow et al., 1996). Likewise, the PEG molecular weight was large (3000-3700), and therefore should not be soluble in supercritical CO2. As shown in Figure 10, reaction occurred with both 18-crown-6 and PEG, but at a slower rate than with tetraheptylammonium cyanide. Again, these results indicate that three phases existed in the reaction system and reaction occurred in the catalyst-rich third phase. The slower rate of reaction with the nonionic catalysts could be a result of many factors, such as different distribution coefficients of benzyl chloride between the CO2 phase and the catalyst phase and variations in anion transport and activation by the different catalysts. The mechanistic differences between tetraheptylammonium cyanide, 18crown-6, and PEG are being investigated. Conclusions The use of supercritical fluids to replace organic solvents in PTC reactions provides new opportunities for environmentally benign processing of heterogeneous reactions, but an understanding of the mechanistic properties of model PTC reactions will be required in order to implement SCF technology in commercial PTC processes. In this investigation, the mechanism of the nucleophilic displacement reaction of benzyl chloride with potassium cyanide was studied between a supercritical CO2 phase and a solid salt phase with a tetraheptylammonium salt as the phase-transfer catalyst. The kinetic data and catalyst solubility measurements indicated that the reaction mechanism involved a catalyst-rich third phase on the surface of solid salt phase, where the reaction actually occurred. In addition, the reaction was carried out with two other catalysts, 18-crown-6 and PEG, and the results from these reactions were also consistent with the proposed mechanism. A three-phase PTC system with reaction
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Received for review October 20, 1997 Revised manuscript received May 14, 1998 Accepted May 14, 1998 IE970741H
