Bis(chloromethyl) - American Chemical Society

Ind. Eng. Chem. Res. 2005, 44, 5417-5426

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Phase-Transfer-Catalyzed Etherification of 4,4′-Bis(chloromethyl)-1,1′-biphenyl with 1-Butanol by Polymer-Supported Catalysis Maw-Ling Wang* Department of Environmental Engineering, Hung Kuang University, Shalu, Taichung County, Taiwan 433, Republic of China

Ze-Fa Lee and Feng-Sheng Wang Department of Chemical Engineering, National Chung Cheng University, Min Hsiung, Chiayi County, Taiwan 621, Republic of China

The synthesis of 4,4′-bis(butanoxymethyl)-1,1′-biphenyl from the reaction of 4,4′-bis(chloromethyl)-1,1′-biphenyl and 1-butanol catalyzed by a polymer with quaternary ammonium groups (triphase catalysis) was carried out in a chlorobenzene/aqueous solution of a KOH two-phase medium. The polymer-supported phase-transfer catalysts were prepared using free-radical polymerization of styrene (St) and 4-vinylbenzyl chloride (4-VBC), followed by quaternized copolymer beads with various tertiary amines. The copolymer particles thus produced are uniform without sieving. This work emphasizes the comparison of the reactivity of the various functional groups attached to the copolymer beads. The effects of the various reaction conditions such as the agitation speed, amount of water, triphase catalyst, potassium hydroxide, organic solvents, temperature, and reusability of the triphase catalyst on the conversion and the reaction rate were investigated. Experimental results show that the triphase catalysts with quaternary ammonium groups facilitate the etherification. A comparison of the reactivity between twophase and triphase catalysis in synthesizing 4,4′-bis(butanoxymethyl)-1,1′-biphenyl was made. Introduction Reactions of hydrophilic compounds with lipophilic compounds are often carried out by using expensive dipolar aprotic solvents, which can dissolve both nonpolar organic and polar inorganic species. However, there is another method, phase-transfer catalysis (PTC), that also facilitates those reactions between a watersoluble reagent and an organic-soluble substance. Quaternary ammonium and phosphonium compounds of appropriate total carbon numbers in alkyl groups have the unique ability to dissolve in both aqueous and organic liquids, thus making these compounds a good choice for most PTC applications. Thus, PTC is a useful tool to increase efficiency, to improve safety, and to reduce environmental impact. Thousands of papers and patents have expanded the use of PTC to a wide range of reactions and processes.1-4 Without such a catalyst, two-phase reactions are often slow or do not occur at all. In comparison with the traditional methods, the biggest advantages in using PTC are as follows: no need for expensive aprotic solvents, simpler workup, shorter reaction time, and lower reaction temperatures. Accordingly, quaternary salts, crown ethers, and cryptands5 have been extensively used as the catalysts6,7 in recent years. However, the separation and recovery of catalysts from solution are difficult with the two-phase solutions. In addition, some of the ammonium and phosphonium * To whom correspondence should be addressed. Tel.: 8864-2631-8652 ext 4175. Fax: 886-4-2652-9226. E-mail: chmmlw@ sunrise.hk.edu.tw.

salts sometimes form stable emulsions, which are also difficult to separate from the two-phase solutions. Fortunately, these problems can be overcome by triphase catalysis (TPC), in which the catalyst is immobilized on the solid support. The term “triphase catalyst” for reaction systems where the phase-transfer catalyst is bound to a solid support was first introduced by Regen8,9 in investigating the cyanide displacement reaction. From an industrial point of view, insoluble catalysts can be easily separated from the reaction medium by filtration or centrifugation. A polymer is the most suitable support for immobilizing the PTC.10,11 The performance of the supported catalyst is strongly dependent on the physical and chemical nature of the immobilized materials.12 Ethers are commercially attractive because of their extensive applications in the fine chemicals industry, such as anti-inflammatory, analgesic, and antipyretic drugs,13 ecologically clean additives to motor oils, nontoxic and high-octane gasoline additives,14-16 plasticizer,17 and perfumery.18 The Eley-Rideal mechanism19 was previously proposed in order to explain the etherification reaction. However, only 8.6% conversion is obtained from the reaction of 4,4′-bis(chloromethyl)-1,1′biphenyl and 1-butanol in the absence of catalyst. In this work, the etherification of 4,4′-bis(chloromethyl)1,1′-biphenyl with 1-butanol, which is catalyzed by a polymer-supported phase-transfer catalyst in an organic solvent/alkaline aqueous solution two-phase medium, is investigated. The reaction is greatly enhanced by adding a small quantity of catalyst. We observed two sequential substitution reactions in the organic solution

10.1021/ie040063g CCC: $30.25 © 2005 American Chemical Society Published on Web 06/07/2005

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Ind. Eng. Chem. Res., Vol. 44, No. 15, 2005

Figure 1. SEM micrograph of copolymerization (St/4-VBC) particles without a cross-linking agent.

to obtain a monosubstituted product [4-(butanoxymethyl)-4′-(chloromethyl)-1,1′-biphenyl] and a disubstituted product [4,4′-bis(butanoxymethyl)-1,1′-biphenyl]. The effects of the various reaction conditions on the conversion and the reaction rate to synthesize 4-(butanoxymethyl)-4′-(chloromethyl)-1,1′-biphenyl and 4,4′bis(butanoxymethyl)-1,1′-biphenyl were carried out. In addition, the apparent rate constants of the two sequential reactions in the organic solution were determined. Experimental Section Materials. 4,4′-Bis(chloromethyl)-1,1′-biphenyl, Dowex 1X8-50 ion-exchange resin, ethanol, tertiary amines [3-(dimethylamino)-1-propylamine (3-DMA-1-PA), 3-(diethylamino)-1-propylamine (3-DEA-1-PA), 3-(dimethylamino)propionitrile (3-DMAPN), and 2-(diethylamino)acetonitrile (2-DEAAN), triethylamine (TEA), tripentylamine (TPA), and trioctylamine (TOA)], quaternary ammonium salts [tetraethylammonium bromide (TEAB), tetrabutylammonium bromide (TBAB), and tetraoctylammonium bromide (TOAB)], 1-butanol, methanol, potassium hydroxide, sodium hydroxide, biphenyl, styrene (St), 4-vinylbenzyl chloride (4-VBC), divinylbenzene (DVB), and organic solvents are all chemicals of analytical grade. Procedure. (1) Preparation of 2 mol % CrossLinking Porous Polymer-Supported Particles. Poly(vinylpyrrolidone) (0.1 g), cetyl alcohol (0.121 g), and 2,2′-azobis(isobutyronitrile) (initiator; 0.164 g) were dissolved in absolute ethanol (80 mL) using ultrasonic irradiation. Then, St (10.2 g), DVB (cross-linking agent; 0.325 g), and 4-VBC (3.815 g) were added to the solution. The mixture was purged with dry nitrogen for 5 min, and the sealed flask was placed in a constant-temperature shaker. Subsequently, the thermostat temperature was increased to 65 °C, and the agitation speed was maintained at 130 rpm for 2 days. The free-radical copolymerization was started in the mixed solution to produce the precipitated copolymer products. These precipitated copolymer products were repeatedly washed with 1% NaOH, 1% HCl, and deionized water five times. Copolymer particles were recovered by filtration and dried in a vacuum oven. Regular particles having an average diameter of about 5 µm without any sieving were obtained and scanned with a JEOL JSM-5410 instrument at a 10-kV accelerating voltage, as shown in Figures 1 and 2.

Figure 2. SEM micrograph of copolymerization (St/DVB/4-VBC) particles with 2 mol % cross-linking. Table 1. Molar Equivalent Activity of the Quaternization of the Copolymer Beadsa

type of catalyst TEA TPA TOA 3-DMA-1-PA 3-DEA-1-PA 3-DMAPN 2-DEAAN Dowex 1X8-50 (commercially available)b

molar equivalence of activity of catalysts (mequiv/g) 0.7002 0.2965 0.2881 0.2452 0.1729 0.2035 0.0631 1.6000

a 0.5 g of copolymer beads (2 mol % cross-linking agent) was placed in a flask with 5 mL of DMF; after 30 min, 5 mL of HNO3 (5 M) was added; the mixture was diluted with deionized water (50 mL). b Adding 2 mL of ammonium iron sulfate (2 M) as the indicator, the solution is treated with 0.02 N NH4SCN and 0.01 N AgNO3 (titration).

(2) Immobilization of Phase-Transfer Catalysts. The copolymer beads (30 g) with a 2 mol % cross-linking agent were equilibrated in N,N-dimethylformamide (DMF; 50 mL) for 12 h at 130 rpm and 50 °C. Then, tertiary amines (30 mL), which are listed in the Materials section, were added to the solution placed in a constant-temperature shaker for 7 days. The quaternized copolymer beads were collected by filtration and washed five times with diethyl ether and methanol consecutively. Finally, the copolymer particles were dried under reduced pressure at 50 °C. The ion pair of the quaternized polymer-supported catalyst forces the analysis of the number of active sites by directly measuring the content of the anion (e.g., halide ions, etc.). Therefore, the indirect Volhard method, which is suitable for analyzing the content of the halide ions, is used. First, an Ag+ aqueous solution in large excess is added to the triphase catalyst, which contains halide ions for reactions. The residues of the Ag+ ions after the reaction are then titrated by a SCN- standard solution, using Fe2+ as the indicator. The equivalent activities of the quaternized resins are listed in Table 1. (3) Experimental Section of the Kinetic Runs. The etherification of 4,4′-bis(chloromethyl)-1,1′-biphenyl was conducted with polymer-supported PTC. The reactor was a 150-mL three-necked Pyrex flask for feeding the reactants, taking samples, and agitating the solu-

Ind. Eng. Chem. Res., Vol. 44, No. 15, 2005 5419

tion. A constant-temperature bath was used for maintaining the desired temperature. In a typical experiment, predetermined quantities of 4,4′-bis(chloromethyl)1,1′-biphenyl (1.01 g, 4 mmol), 1-butanol (11.12 g, 150 mmol), potassium hydroxide (20 g), a polymer-supported catalyst (0.5 mmol), and biphenyl (internal standard; 0.46 g, 3 mmol) were added to 50 mL of chlorobenzene and 20 mL of water at the desired temperature. The aqueous-phase reactant (1-butanol, 150 mmol) was taken in large excess over the organic-phase reactant [4,4′-bis(chloromethyl)-1,1′-biphenyl, 4 mmol]. The mixed solution was stirred continuously using a mechanical mixer equipped with a poly(tetrafluoroethylene) halfmoon blade rotating at fixed agitation speeds for 3 h. Small quantities of samples were withdrawn at chosen time intervals and were immediately added to 5 mL of methanol to quench the reaction. Subsequently, the samples were analyzed by a high-performance liquid chromatograph (HPLC). The concentrations of the reactants and products were quantified using a HPLC with mobile-phase acetonitrile and deionized water. HPLC was carried out using Shimadzu SPD-10AVP (system controller), SPD-M10A (detector), and LC10ATVP (pump) with analyzed software glass vp 5.0 and a photodiode array detector (UV wavelength of 269 nm). Acetonitrile and deionized water were used as the mobile phase in the HPLC. A Lichrosorb RP-18e (5 µm, 250 nm) column (Applied Merck Co.) was used to separate the components and to analyze them experimentally. Also, the concentration gradient of the eluent in the HPLC is listed in the following:

time

module

0.01 3.00 5.00 8.00 12.00 15.00 16.00 18.00 20.00 30.01

pumps pumps pumps pumps pumps pumps pumps pumps pumps SCL-10Avp

event acetonitrile acetonitrile acetonitrile acetonitrile acetonitrile acetonitrile acetonitrile acetonitrile acetonitrile STOP

Scheme 1

Reaction Kinetics and Mechanism The overall reaction for the present system is

value (%) conc conc conc conc conc conc conc conc conc

60 60 65 70 95 95 90 60 60 60

The residual times of the monosubstituted and disubstituted products in HPLC spectra are 15.0 and 17.5 min, respectively. The products are also identified by NMR and elemental analysis (EA), respectively. The reaction mixture, as well as monosubstituted and disubstituted products, was separated using the pressurized column chromatograph19 (silica gel as the adsorbent and dichloromethane as the eluent) and were identified by recording on a Bruker advance spectrometer (600 MHz) for functional groups and a mass spectrometer for molecular weight. The reactivity of an alkoxide ion is higher than that of a hydroxide ion.20 s Furthermore, the selectivity constant21 KRO/OH is ap3 proximately 10 . Thus, only substituted reaction of an alkoxide occurs. No 4,4′-bis(hydroxymethyl)-1,1′-biphenyl product is generated during or after the reaction. KsRO/OH

[P+OH] + [RO-] y\z [Q+RO-] + [OH-] Byproducts were not observed during or after the reaction.

As shown in the above equation, two chlorides of 4,4′bis(chloromethyl)-1,1′-biphenyl are each substituted by a butanoxide group, i.e., monosubstituted product [4-(butanoxymethyl)-4′-(chloromethyl)-1,1′-biphenyl] and disubstituted product [4,4′-bis(butanoxymethyl)-1,1′-biphenyl]. For that, the fundamental mechanism proposed is given in Scheme 1. The two main reaction mechanisms in heterogeneous catalysis are the Langmuir-Hinshelwood and EleyRideal reactions.19 The Langmuir-Hinshelwood mechanism15 is a type of surface catalysis in which the reaction occurs between species that are adsorbed on the surface. The Eley-Rideal mechanism is also a type of surface catalysis in which the liquid- or gas-phase components can react with species already adsorbed on a surface. Here, the Eley-Rideal mechanism is proposed to explain the reaction steps in this work. Alkanol reacted with potassium hydroxide to form potassium alkoxide (RO-K+) in the aqueous phase and then transferred from the bulk phase to the active sites of the triphase catalyst. The ion exchange between the chloride anion and alkoxide anion takes place on the polymer-supported surface. Then, the formed polymersupported phase-transfer catalyst P+OR- ion pairs further reacted with the organic reactant [4,4′-bis(chloromethyl)-1,1′-biphenyl] to produce a monosubstituted product [4-(butanoxymethyl)-4′-(chloromethyl)1,1′-biphenyl]. Subsequently, the monosubstituted product may further react with P+OR- to successively

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generate a dichloro-substituted product [4,4′-bis(butanoxymethyl)-1,1′-biphenyl]. For reaction control, the consuming rate of the reactant and the rate of production are expressed as

d[C12H8(CH2Cl)2]o ) dt ηkR1w[P+OR-]s[C12H8(CH2Cl)2]o (1) d[C12H8(CH2Cl)(CH2OR)]o ) dt ηkR1w[P+OR-]s[C12H8(CH2Cl)2]o ηkR2w[P+OR-]s[C12H8(CH2Cl)(CH2OR)]o (2) d[C12H8(CH2OR)2]o ) dt ηkR2w[P+OR-]s[C12H8(CH2Cl)(CH2OR)]o (3) where η is the effectiveness factor of the reaction; kR1 and kR2 are the first and second intrinsic rate constants of the organic-phase reactions, respectively; w is the loading of the catalyst (g/cm3 of the liquid phase); the subscripts s and o represent the characteristics of the species at the solid phase and in the organic phase, respectively; C12H8(CH2Cl)2, C12H8(CH2Cl)(CH2OR), and C12H8(CH2OR)2 denote 4,4′-bis(chloromethyl)-1,1′-biphenyl (reactant), 4-(butanoxymethyl)-4′-(chloromethyl)1,1′-biphenyl (monochloro-substituted product), and 4,4′bis(butanoxymethyl)-1,1′-biphenyl (dichloro-substituted product), respectively. During the reaction, alkanol in large excess was used. Furthermore, the catalyst loading, w, and the effectiveness factor, η, can also be considered as constants. The content of the polymer-supported phase-transfer catalyst P+OR- can also be considered as a constant. In the absence of both external and internal resistance of mass transfer, the apparent rate constants were estimated. Accordingly, for a pseudo-first-order reaction, we have

-

d[C12H8(CH2Cl)2]o ) kapp,1[C12H8(CH2Cl)2]o dt

(4)

d[C12H8(CH2Cl)(CH2OR)]o ) dt kapp,1[C12H8(CH2Cl)2]o kapp,2[C12H8(CH2Cl)(CH2OR)]o (5) d[C12H8(CH2OR)2]o ) kapp,2[C12H8(CH2Cl)(CH2OR)]o dt (6) where

kapp,1 ) ηkR1w[P+OR-]s

(7)

kapp,2 ) ηkR2w[P+OR-]s

(8)

Upon integration of eq 4, the following result is obtained:

-ln(1 - X) ) kapp,1t

(9)

where X is the conversion of 4,4′-bis(chloromethyl)-1,1′biphenyl (reactant)

X)1-

[C12H8(CH2Cl)2]o [C12H8(CH2Cl)2]o,i

(10)

where the subscript i represents the initial condition of the species. Thus, a plot of -ln(1 - X) vs time t gives a slope that represents kapp,1. When eqs 5 and 9 are combined, the following equation is obtained:

[C12H8(CH2Cl)(CH2OR)]o ) kapp,1 [C H (CH2Cl)2]o,i[exp(-kapp,1t) kapp,2 - kapp,1 12 8 exp(-kapp,2t)] (11) where [C12H8(CH2Cl)2]o,i is the initial concentration of the organic reactant. When kapp,1 is determined, kapp,2 can also be estimated from eq 11 using a computer program (software Fortran 90). Results and Discussion In this work, the reaction of St with 4-VBC in a crosslinking agent DVB (0, 2, and 20 mol %) was successfully prepared by free-radical polymerization in absolute ethanol using 2,2′-azobis(isobutyronitrile) as the initiator. The polymer-supported PTC promoted the etherification reaction. Using EA to analyze the content of the triphase catalyst pellet, it was found that chloride does exist. The catalytic activity of the polymer support comes directly from the immobilization of trialkylamine. Also, the molar equivalence of the activity of the triphase catalyst is obtained by measuring the content of the chloride ions in the catalyst pellet using the Volhard method. As stated, portions of the chlorides in the polymer-supported pellet are ionized by immobilizing trialkylamine on the polymer-supported pellet, i.e.

P-CH2Cl + R3N f P-CH2-N+(R)3ClThen, only the ionized chlorides possess catalytic activity. The results showing the equivalent activity of the polymer-supported catalyst in using various tertiary amines are shown in Table 1. Among the reagents, Dowex 1X8-50 possessess a higher molar equivalent quantity in activity. Further, the molar equivalent activity (mequiv/g) of the triphase catalyst in using tertiary amines of an alkyl group without an amino group is larger than that of the tertiary amines of an alkyl group with an amino group. In principle, three products are probably produced from the reaction of polystyrene and 3-DMA-1-PA [(CH3)2NCH2CH2CH2NH2] for immobilization as shown in the following:

Ind. Eng. Chem. Res., Vol. 44, No. 15, 2005 5421 Scheme 2

If product II is generated, a further reaction with 4,4′bis(chloromethyl)-1,1′-biphenyl takes place, i.e., Scheme 2. However, there is one tertiary amine group and one primary amine group on the (CH3)2NCH2CH2CH2NH2 molecule. The kb values of the primary amine and tertiary amine are about 4.4 × 10-4 and 5.5 × 10-5, respectively. Obviously, the reactivity of the primary amine is larger than that of the tertiary amine. Thus, the chemical II will probably be the main product from the reaction of polystyrene and (CH3)2NCH2CH2CH2NH2 if one judges the reactivity based on the difference between primary and tertiary amines. However, a molecule HCl has to be removed from the reaction of polystyrene [P-(C6H5)CH2Cl] and (CH3)2NCH2CH2CH2NH2 to produce product II. Therefore, the reaction of P-(C6H5)CH2Cl and (CH3)2NCH2CH2CH2NH2 is favorable to proceed in an alkaline solution to neutralize HCl under these circumstances. In fact, there is no alkali compound added to the reaction solution during the immobilization process. Therefore, probably product II will be produced from the immobilization step, but it is not the main product. To confirm the products during the immobilization process, three experimental evidences were verified in this work. First, as noted by McMurry,26 there is a pair of absorbances between 3350 and 3450 cm-1 for a primary amine group and there is only one single absorbance at 3350 cm-1 for a secondary amine from the IR spectrum analysis. In this work, we also obtained the IR spectrum of the polymer support. Of course, one still cannot confirm whether product I or IV is produced by viewing the IR of the amine and polymer support, respectively. Nevertheless, the immobilization step really produces a chloride ion by using the Volhard method to examine the sample. Therefore, there is no product II produced. Second, the transmittance in a high wavenumber is low for a sample of the quaternized polymer support. Therefore, we also quaternized 3-DEA-1-PA with benzyl chloride (or benzyl bromide, chlorobutane, or bromobutane) for auxiliary proof in this work. The quaternized products are then also inspected by IR. Upon further investigation of the IR spectra of other species (i.e., of 3-DEA-1-PA, of benzyl chloride, of benzyl chloride + 3-DEA-1-PA, of benzyl bromide + 3-DEA-1-PA, of chlorobutane + 3-DEA-1-PA), all of these results indicate that no secondary amine is produced; i.e., no product II is produced from these auxiliary proofs. Third, the pH value of the solution during the immobilization process was also examined during the period of the immobilization process. The solution is found to be still basic rather than acidic. However, the solution should produce HCl if product II is supposed to be generated. This evidence also confirms that no secondary amine (or product II) is produced. In summary, the experimental results obtained from the catalytic reaction of etherification will not be affected by the structures of the catalytic sites, even if

Figure 3. Plot of -ln(1 - X) vs time with various agitation speeds in TPC: 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 3 mmol of an internal standard, 50 mL of chlorobenzene, 0.5 mequiv of TEA on a polymer support (2 mol % crosslinking agent), 20 g of KOH, and 20 mL of water at 45 °C.

product II is generated. The reason is that either the catalytic sites obtained from only product I or the structures of the catalytic sites produced by product II will generate the catalytic sites. These catalytic sites are then employed to catalyze the etherification on our reaction system. Photographs of the microporous pellet taken by scanning electron microscopy (SEM) are shown in Figures 1 and 2. A uniform particle size of the polymer pellets is obtained without sieving. The effects of the reaction conditions were investigated, including the agitation speed, triphase catalysts and their amounts, amount of water, amount of triphase catalyst, organic solvents and their amounts, amount of potassium hydroxide, temperature, and reuse of the triphase catalysts. (1) Effect of the Agitation Speed. The overall reactivity of a phase-transfer reaction catalyzed by a polymer-supported catalyst depends on its intrinsic reactivity and mass-transfer processes, including bulk diffusion and intraparticle diffusion of the reagents.22 This work focuses on the determination of the masstransfer effect. The ion-exchange reaction in the aqueous phase is rapid compared to the reaction in the organic phase. Conceivably, the concentration of 1-butanol in the aqueous phase (150 mmol of 1-butanol in 20 mL of water) is large in excess in stoichiometric quantity compared to that of 4,4′-bis(chloromethyl)-1,1′-biphenyl (organic-phase reactant, 4 mmol), so that the compound in the organic phase is considered as the rate-limiting component. A plot of the experimental data with various agitation speeds is shown in Figure 3, indicating that the reaction follows a pseudo-first-order rate law with respect to the limiting reactant, 4,4′-bis(chloromethyl)1,1′-biphenyl. Furthermore, the reaction occurs within the kinetic plateau at agitation speeds larger than 400 rpm; i.e., the diffusion of organic and inorganic reactants to the surface of the copolymer beads is not the limiting factor of the overall reactivity at moderate stirring. For agitation speeds of less than 200 rpm, the reaction is mass-transfer-controlled. In fact, the organic phase is not fully dispersed within the aqueous phase at low agitation speeds, and increasing the agitation speed mainly results in the organic phase being more fully dispersed within the aqueous phase. The following

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Figure 4. Plot of -ln(1 - X) vs time with various agitation speeds in TPC: 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 3 mmol of an internal standard, 50 mL of chlorobenzene, 0.5 mequiv of TEA on a polymer support (20 mol % crosslinking agent), 20 g of KOH, and 20 mL of water at 45 °C.

Figure 6. Conversion of 4,4′-bis(chloromethyl)-1,1′-biphenyl vs time with various phase-transfer catalysts in a two-phase reaction: 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 0.5 mmol of a phase-transfer catalyst, 3 mmol of an internal standard (biphenyl), 50 mL of chlorobenzene, 20 g of KOH, and 20 mL of water at 800 rpm and 45 °C. Table 2. Effect of Forming P+OR- on a Triphase Catalysta

entry

type of catalyst

amount of potassium hydroxide (g)

monosubstituted product (mmol)

1 2 3 4 5 6 7

TEA TEA TEA TEA TEA TPA TOA

20 25 30 35 40 20 20

0.403 0.416 0.421 0.390 0.372 0.384 0.338

a Step 1: 0.5 mequiv of a triphase catalyst (2 mol % cross-linking agent), 150 mmol of 1-butanol, 20 g of KOH, 50 mL of chlorobenzene, 20 mL of H2O, 1 h of agitation, washing with deionized water and THF. Step 2: 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 20 g of KOH, 50 mL of chlorobenzene, 20 mL of H2O, 3 mmol of an internal standard.

Figure 5. Conversion of 4,4′-bis(chloromethyl)-1,1′-biphenyl vs time with various catalysts in TPC: 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 0.5 mequiv of a triphase catalyst (2 mol % cross-linking agent), 3 mmol of an internal standard (biphenyl), 50 mL of chlorobenzene, 20 g of KOH, and 20 mL of water at 800 rpm and 45 °C.

experiments were carried out with mechanical stirring at 800 rpm, so the process may be treated as chemicalreaction-controlled. Figure 4 shows the effect of the agitation speed on the conversion in using 0.5 mequiv of the triphase catalyst with 20 mol % cross-linking agent. The conversion is increased with an increase in the agitation speed up to 1200 rpm. This behavior is different from that of the triphase catalyst with 2 mol % cross-linking agent. The major difference between Figures 3 and 4 is their porosity. A more compact (or less porosity) is obtained using a high percent of cross-linking agent. It is obvious that the reaction is more dominated by mass-transfer control for the reaction system shown in Figure 4 than for that shown in Figure 3. (2) Effect of Triphase Catalysts. Different triphase catalysts were used to assess their effectiveness in the etherification, and the nature of the alkyl groups on the quaternized site was investigated. Figures 5 and 6 show the conversion of 4,4′-bis(chloromethyl)-1,1′-biphenyl (the limiting reagent) vs time for various triphase

catalysts under the same molar equivalent quantity in activity and homogeneous catalysts (Q+X-) with the same concentration. Apparently, the amines with long alkyl groups (e.g., 3-DEA-1-PA) are relatively unfavorable for the formation of the ion pair P+OR- compared with TEA, TPA, and TOA. It is difficult for the alkoxide group (OR-) to adsorb on the active site. To ensure the formation of P+OR-, several independent experimental runs were first carried out under the same experimental reaction conditions without adding organic reactant [4,4′-bis(chloromethyl)-1,1′-biphenyl] for a 1-h reaction. Different triphase catalysts were then recovered by filtration and washed thoroughly with deionized water and tetrahydrofuran (THF). Afterward, the triphase catalysts and organic-phase reactant were added to the solution for 2 days. The results for the yield of the monosubstituted product obtained from the reactions are shown in Table 2. The results show that a tertiary amine of longer alkyl groups attached to the polymer support possesses fewer active sites, P+OR- . The orders of the reactivity for these triphase catalysts are TEA > TPA > TOA and 3-DMA-1-PA >3-DEA-1-PA. It is noted that the reactivity of the polymer-supported TEA is much higher than that of the TEAB; this is because the more hydrophobic character of the polymer support will be more compatible with the organic phase, so the reaction rate is increased. Further, the reduced ef-

Ind. Eng. Chem. Res., Vol. 44, No. 15, 2005 5423 Table 3. Effect of Various Triphase Catalysts on the Apparent Rate Constantsa catalyst

kapp,1 (10-3 min-1)

kapp,2 (10-3 min-1)

TEA TPA TOA 3-DMA-1-PA 3-DEA-1-PA 3-DMAPN 2-DEAAN Dowex 1X8-50 TEAB TBAB TOAB

6.67 4.75 4.60 7.52 1.40 5.44 7.21 1.17 2.91 6.09 6.67

2.24 1.37 1.30 3.15 0.52 1.52 3.06 0.34 1.05 2.13 2.35

a 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 0.5 mequiv of a triphase catalyst (2 mol % cross-linking agent), 3 mmol of an internal standard (biphenyl), 50 mL of chlorobenzene, 20 g of KOH, and 20 mL of water at 800 rpm, 45 °C, and 3 h.

ficiency of 3-DEA-1-PA relative to 3-DMA-1-PA is due to the reduced number of active sites of the polymersupported catalyst. The molar equivalent activity of the catalyst (mequiv/g) directly reflects the number of active sites of the polymer-supported catalyst. Table 1 lists the activities of the various catalysts. The mequivalents per gram value of 3-DMA-1-PA is larger than that of 3-DEA1-PA, in which the number of active sites of 3-DMA-1PA is larger than that of 3-DEA-1-PA. Furthermore, experimental results indicated that the amino group contributed to the etherification reaction. Amine is more basic than alcohols, ethers, or water. From the knowledge given by Volhard,21 amine can be considered an acid or a base. The Ka and Kb values of amine are 10-35 and 10-4, respectively. Therefore, it is favorable for amine to form RNH3+ rather than RNH- in the presence of water. Therefore, RNH3+ still exists in a small quantity in an alkaline aqueous solution, i.e.

When an amine is dissolved in water, an equilibrium is quickly established in which water acts as a protic acid and transfers a proton to the amine. For the reaction

RNH2 + H2O h RNH3+ + OHthe RNH3+ cation also acts as another active site that facilitates the etherification reaction. In addition, the experimental results show that the triphase catalyst with nitrile groups has a higher activity. A slight hydrophilization of polymer-supported PTC was achieved with nitrile groups, and that facilitated the formation of the ion pair P+OR-. The catalyst with an R-cyanomethyl group will form an ammonium ylide, which may deprotonate 1-butanol to enhance the reaction. The corresponding apparent rate constants kapp,1 and kapp,2 are listed in Table 3. Conversely, the activities of the two-phase phasetransfer catalysts are in the order TOAB > TBAB > TEAB, which showed that a quaternary ammonium

Figure 7. Plot of the effect of the amount of water on the apparent rate constant in TPC (immobilizing TEA on a polymer support): 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 0.5 mequiv of a triphase catalyst (2 mol % cross-linking agent), 3 mmol of an internal standard (biphenyl), 50 mL of chlorobenzene, and 20 g of KOH at 800 rpm and 45 °C.

cation with a higher total carbon number in the alkyl groups provides a higher activity. The reason for these phenomena was that a higher total carbon number in the alkyl groups of the tertiary amine has hydrophobic properties. Considering the hydrophobic nature of the catalyst cation, it is possible to transport anions into the organic phase, so the more water-soluble TEAB provides less reactivity. Conversely, TOAB, which possesses 32 carbon atoms, is extremely organic-soluble, so a higher activity in the organic phase is obtained. Therefore, the reaction rate is increased with an increase in the total carbon number. (3) Effect of the Amount of Water. In this work, the volume of water was increased from 0 to 80 mL. Figure 7 shows the effect of the water volume on the two apparent rate constants, indicating a notable increase in the rate of reaction when the volume of water is decreased from 40 to 0 mL. However, there is no appreciable change of the apparent rate constants for over 40 mL of water. When an alkoxide anion is generated, it would form an active intermediate P+ORimmediately on the surface of the polymer-supported catalyst rather than in the aqueous phase because of the low capacity of the water in the lower amount of water condition. Hence, the reaction is enhanced with lower amounts of water, although when the amount of water is over 40 mL, the reaction rate will not change significantly. Therefore, the concentration of OR- should reach an equilibrium state between the aqueous and solid polymer-supported catalyst pellets. (4) Effect of the Amount of Triphase Catalyst. The reaction was carried out in the absence of catalyst in order to investigate the reactivity of the triphase catalysts. In a blank reaction, the conversion was very low, with only an 8.6% yield obtained after 3 h. A plot of the apparent rate constants as a function of the amount of triphase catalysts (TEA) is shown in Figure 8. These data show that the rate of etherification is linearly dependent on the amount of catalyst. Also, it is noted that the reactions achieve almost 100% conversion using a higher catalyst loading. This suggests that the reaction was a solely irreversible reaction. (5) Effect of the Organic Solvents. Chlorobenzene, chloroform, dibutyl ether, toluene, benzene, and cyclo-

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Figure 8. Plot of the effect of the amount of triphase catalysts on the apparent rate constant in TPC (immobilizing TEA on a polymer support): 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 3 mmol of an internal standard (biphenyl), 50 mL of chlorobenzene, 20 g of KOH, and 20 mL of water at 800 rpm and 45 °C. Table 4. Effect of the Organic Solvents on the Two Organic-Phase Apparent Rate Constantsa organic solvent

EN T

chlorobenzene ( ) 5.6) chloroform ( ) 4.8) dibutyl ether ( ) 2.8) toluene ( ) 2.4) benzene ( ) 2.3) cyclohexanone ( ) 18.3)

0.188 0.259 0.071 0.099 0.111 0.281

swelling kapp,1 kapp,2 value (103 min-1) (103 min-1) 1.81 1.59 1.27 1.86 2.09 1.90

6.67 3.37 2.58 5.49 5.84 7.20

2.87 1.92 0.94 2.21 2.43 3.19

a 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 0.5 mequiv of a triphase catalyst (2 mol % cross-linking agent), 3 mmol of an internal standard, 20 g of KOH, 20 mL of H2O, and 50 mL of an organic solvent at 800 rpm, 45 °C, and 3 h.

hexanone were chosen as the organic solvents. The reactions were carried out under the same molar equivalent activity for all triphase catalysts. From the experimental result shown in Table 4, the biggest apparent rate constant was obtained by choosing cyclohexanone, which possesses the highest dielectric constant, as the organic solvent. However, the apparent rate constants do not correlate well with the dielectric constants. In general, chloroform can generate a trichloromethyl anion and dichlorocarbene, and cyclohexanone can generate an enolate anion. The reasons for using chloroform and cyclohexanone as the organic solvents are to observe the reaction affected by the variation of the dielectric constant and to observe the reaction affected by the change of the environment due to the reaction of the organic solvent. Chloroform and dibutyl ether, which have higher dielectric constants, exhibit lower apparent rate constants. The main reason for this is that the molecular structure of the polymer support contains an aromatic group, so it swells more easily with organic solvents such as chlorobenzene, toluene, cyclohexanone, and benzene. The swelling values (volume of the wet swollen triphase catalyst/volume of the dry triphase catalyst) of the polymer support in different organic solvents are also listed in Table 4. A larger degree of swelling denotes that the triphase catalysts were more compatible with the organic solvent; i.e., an organic solvent intimates the triphase catalyst. From these data, the lowest swelling value was 1.27 using the dibutyl ether as the organic solvent, which also means that the active sites were largely inaccessible for

Figure 9. Plot of the effect of the amount of potassium hydroxide on the apparent rate constant in TPC (immobilizing TEA on a polymer support): 4 mmol of 4,4′-bis(chloromethyl)-1,1′-biphenyl, 150 mmol of 1-butanol, 0.5 mequiv of a triphase catalyst (2 mol % cross-linking agent), 3 mmol of an internal standard (biphenyl), 50 mL of chlorobenzene, and 20 mL of water at 800 rpm and 45 °C.

reactivity in a low-swelling organic solvent. Therefore, the polarity of the solvent and the swelling property are the two main factors of the organic solvents affecting the reaction rate or conversion. Another solvent parameter, Reichardt’s solvatochromic scale EN T , which is an index for the degree of ionization, was better related with the apparent rate constant, except for chloroform.23-25 (6) Effect of the Amount of KOH. This work also investigates the effect of the amount of potassium hydroxide on the conversion, with experimental results as shown in Figure 9. It can be seen that the apparent rate constants increased with an increase in the amount of KOH up to 30 g and then decreased with a further increase in the amount of KOH over 30 g of KOH. Thus, a optimum level of potassium hydroxide exists, and the reaction environment is changed by increasing the amount of KOH. In general, the amount of OR- is increased with an increase in the amount of KOH because of the reaction of 1-butanol and KOH. Hence, P+OR- is also increased with an increase in the amount of KOH, so the reaction rate is increased with an increase in the amount of KOH even though the affinity of hydroxide anions with the triphase catalyst is smaller than that of chloride and alkoxide anions with the triphase catalyst. However, the addition of a huge amount of KOH causes a reaction with the active sites, which forms P+OH-, thus blocking the substitution reaction. The number of active sites naturally decreases with a further increase in the amount of KOH. Therefore, the reaction rate then decreases with an increase in the amount of KOH. Several independent experimental runs were carried out without the addition of an organic reactant for 1 h with various amounts of KOH. Then, the triphase catalysts obtained from the reactor were washed with deionized water and THF three times, and the typical experiment was run without adding 1-butanol. Table 2 shows that the less monosubstituted product formed means that there was less P+OR- in the triphase catalysts. (7) Effect of the Temperature. The effect of the temperature on the conversion for various triphase catalysts was studied in the range of 45-65 °C. It is clear that increasing the reaction temperature enhances

Ind. Eng. Chem. Res., Vol. 44, No. 15, 2005 5425 Table 5. Activation Energies for Various Triphase Catalystsa triphase catalyst

Ea1 (kcal/gmol)

Ea2 (kcal/gmol)

TEA TPA TOA 3-DMA-1-PA 3-DEA-1-PA 3-DMAPN 2-DEAAN Dowex 1X8-50

15.43 15.48 15.20 17.92 17.28 15.49 16.68 14.35

17.41 18.54 19.65 23.49 18.16 17.95 23.21 19.87


Table 6. Stability Studies of the Polymer-Supported PTC on the Etherification of the 4,4′-Bis(chloromethyl)-1,1′-biphenyla species TEA

Dowex 1X8-50

3-DMA-1-PA

no. of reuses

conversion (%)

fresh 1 2 3 fresh 1 2 3 fresh 1 2 3

69.0 56.2 38.2 35.6 18.5 18.3 18.2 18.0 74.2 69.2 69.0 68.0


the molecular collision between the reactant and the active sites, and the activation energies of the triphase catalysts are listed in Table 5. As shown in Table 3, it is noteworthy that the apparent rate constant of 3-DMA1-PA is the highest among the catalysts used in this work and the corresponding activation energy is also the highest. This can be explained by the apparent frequency factor of the Arrhenius equation, including the stereo factor and collision frequency. Thus, by its structure, 3-DMA-1-PA has more active sites, leading to more collisions and less stereo hindrance. These high activities also confirm the small mass-transfer resistance. (8) Reusability of the Triphase Catalysts. The reusability of the triphase catalysts was verified by employing them four times. After each run, the triphase catalysts were washed thoroughly with deionized water and diethyl ether and dried in an oven at 80 °C for 1 day. For comparative purposes, Dowex 1X8-50, polymersupported TEA, and 3-DMA-1-PA were chosen for investigating their reusabilities. Table 6 shows the relation between the reusability of the triphase catalysts and the conversion of 4,4′-bis(chloromethyl)-1,1′-biphenyl. The activity of Dowex 1X8-50 remained at almost the same low value for the four runs for this etherification. The initial activity of TEA was high, but it has low stability, and when used for the fourth time, only half of the conversion of the organic reagent was obtained. 3-DMA-1-PA, which had the highest activity, also exhibited excellent reusability. Except for the marked decrease in the first cycle, the conversion of the

organic reactant decreased only slightly. As can be inferred from the presented data, Dowex 1X8-50 and 3-DMA-1-PA are more stable than TEA. Consequently, 3-DMA-1-PA has not only superior activity but also high reusability for the etherification. Conclusion In this work, the triphase catalyst of the micropore was successfully prepared from the polymerization of St monomer and 4-VBC, followed by the quaternized copolymer particles with various tertiary amines. A uniform particle size of the polymer pellets was obtained with no sieving. Furthermore, the quantities of the active sites were measured in some effect sections to support the experimental results. The reaction of 4,4′bis(chloromethyl)-1,1′-biphenyl and 1-butanol to synthesize 4,4′-bis(butanoxymethyl)-1,1′-biphenyl was successfully catalyzed by the triphase catalyst. This etherification is mass-transfer-controlled at low agitation speeds (400 rpm). The conversion (or the reaction rate) is decreased with an increase in the amount of water and is increased with an increase in the amount of the triphase catalyst and in the temperature. The reaction rate is increased up to a certain period and then decreased with increasing amounts of KOH. Among the various polymer-supported triphase catalysts, 3-DMA1-PA was found to be the most efficient catalyst, with a reaction following pseudo-first-order kinetics. Some of the triphase catalysts can be reused without significant loss of reactivity, and their stability is sufficiently high to ensure long-term use. Acknowledgment The authors thank the National Science Council for financial support under Grant NSC-89-2214-E-194-0. Literature Cited (1) Demhlow, E. V.; Demhlow, S. S. Phase Transfer Catalysis, 3rd ed.; VCH Publishers: Weinheim, Germany, 1993. (2) Sasson, Y., Neumann, R., Eds. Handbook of Phase Transfer Catalysis; Chapman & Hall: London, U.K., 1997. (3) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives; Chapman & Hall: New York, 1994. (4) Weber, W. P.; Gokel, G. W. Phase Transfer Catalysis in Organic Synthesis; Springer-Verlag: New York, 1977. (5) Izatt, R. M.; Pawlak, K.; Bradshaw, J. S.; Bruening, R. L. Thermodynamic and Kinetic Data for Macrocycle Interactions with Cations and Anions. Chem. Rev. 1991, 91, 1721-2085. (6) Wang, M. L.; Wu, H. S. Kinetic Study of the Substitution Reaction of Hexachlorocyclotriphosphazene with 2,2,2-Trifluoroethanol by Phase-Transfer Catalysis and Separation of the Products. Ind. Eng. Chem. Res. 1990, 29, 2137-2142. (7) Wang, M. L.; Tseng, Y. H. Phase Transfer Catalytic Reaction of Dibromo-o-Xylene and 1-Butanol in Two-Phase Solution. J. Mol. Catal. A: Chem. 2002, 179, 17-26. (8) Regen, S. L. Triphase Catalysis. J. Am. Chem. Soc. 1975, 97, 5956-5957. (9) Regen, S. L. Triphase Catalysis. Kinetics of Cyanide Displacement on 1-Bromooctane. J. Am. Chem. Soc. 1976, 98, 62706274. (10) Regen, S. L. Triphase Catalysis. Applications to Organic Synthesis. J. Org. Chem. 1977, 42, 875-879. (11) Hodge, P.; Sherrington, D. C. Polymer-Supported Reactions in Organic Chemistry; Wiley: London, 1980. (12) Akelah, A.; Sherrington, D. C. Application of Functionalized Polymers in Organic Synthesis. Chem. Rev. 1981, 81, 557587.

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(13) Yadav, G. D.; Krishnan, M. S. Etherification of β-Naphthol with Alkanols Using Modified Clays and Sulfated Zirconia. Ind. Eng. Chem. Res. 1998, 37, 3358-3365. (14) Yadav, G. D.; Joshi, A. V. Etherification of tert-Amyl Alcohol with Methanol over Ion-Exchange Resin. Org. Process Res. Dev. 2001, 5, 408-414. (15) Nunan, J. G.; Klier, K.; Herman, R. G. Methanol and 2-Methyl-1-Propanol (Isobutanol) Coupling to Ethers and Dehydration over Nafion H:Selectivity, Kinetics, and Mechanism. J. Catal. 1993, 139, 406-420. (16) Harmer, M. A.; Sun, Q. Solid Acid Catalysis Using IonExchange Resins. Appl. Catal. A 2001, 221, 45-62. (17) Joshi, S. R.; Sawant, S. B.; Joshi, J. B. Process Development Aspects of Production of Dibenzyl Ether. Org. Process Res. Dev. 1999, 3, 17-27. (18) Saha, B. Ion-Exchange Resin Catalysed Etherification of Dicyclopentadiene (DCPD) with Methanol. React. Funct. Polym. 1999, 40, 51-60. (19) Satrio, J. A. B.; Glatzer, H. J.; Doraiswamy, L. K. Triphase Catalysis: A Rigorous Mechanistic Model for Nucleophilic Substitution Reactions Based on a Modified Langmuir-Hinshelwood/ Eley-Rideal Approach. Chem. Eng. Sci. 2000, 55, 5013-5033. (20) McMurry, J. Organic Chemistry, 4th ed.; Brooks/Cole Publishing Co.: Pacific Grove, CA, 1996; p 381.

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Received for review February 20, 2004 Accepted May 5, 2005 IE040063G

Bis(chloromethyl) - American Chemical Society

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