**2.4 N-Alkylation**

The synthesis of 1-(3-phenylpropyl)-pyrrolidine-2,5-dione was successfully carried out [23] from the reaction of succinimide with 1-bromo-3-phenylpropane in a small amount of KOH and organic solvent solid–liquid phase medium under phase-transfer catalysis (PTC)

Role of Mass Transfer in Phase Transfer Catalytic Heterogeneous Reaction Systems 701

0 30 60 90 120 150 180

T i m e ( m i n )

The reaction between sodium sulfide and *n*-bromobutane to synthesize di-*n*-butyl sulfide was carried out for in an organic solvent/alkaline solution two-phase medium under phase transfer catalysis (PTC) conditions [65]. The overall reaction is presented in Scheme 4. In the two-phase reaction, mass transfer resistance is an important factor in affecting the reaction rate. In general, either the organic or the aqueous solution can be dispersed in smaller droplet size by agitating the two-phase solution, so, the contact area of two phases is increased with higher agitation speed. The flux of the two-phase mass transfer is also highly dependent on the flow condition (e.g. agitation speed). Fig. 8 shows the dependence of the apparent rate constant (*kapp,1*) on the agitation speed. For agitation speeds less than 350 rpm, both mass transfer and reaction resistance are important in determining the overall reaction rate. In this work, the reaction rate does not significantly change for agitation speeds larger than 350 rpm, and the mass transfer resistances of the active catalyst between the two phases are the same for agitation speed over 350 rpm. Hence, it is obvious that the reaction in organic phase is the rate-controlling step for agitation speed larger than 350 rpm under the standard reaction conditions. Below 50 rpm, the reaction rate is quite low because the two-phase solutions do not mix well and layering is clearly observed. Over 100 rpm, the ivory-white dispersion phase occurs. However, the phenomenon of constancy of the reaction rate constant over a certain agitation speed widely exists in PTC reactions, which are formulated based on an extraction model. Wang and Tseng [66], Jayachandran et al. [67], Park et al. [68], Wang and Wu [69] and Do and Chou [70], proposed the agitation speeds

Fig. 7. Plot of -ln(1 - X) of 1-bromo-3-phenylpropane versus time with various agitation speeds; 9.0 × 10-2 mol of succinimide, 1 g of KOH, 0.4 g of TOAB, 6.0 × 10-3 mol of 1-bromo-3-phenyl-propane, 50 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 40 °C.

0.0

**2.5 S-Alkylation** 

(Adapted from Ref. [23], by permission)

0.4

0.8


1.2

1.6

2.0

A g i t a t i o n s p e e d 0 r p m 100 r p m 200 r p m 400 r p m 600 r p m 800 r p m 1000 r p m 1200 r p m

almost water-free conditions (Scheme 3). For a solid-liquid phase reaction system, agitation increases the kinetic energy of the system and tends to speed up the reaction until a limiting factor is reached. After this the reaction rate is not affected by increasing stirring rates. Therefore, the effect of the agitation speed on the conversion and the reaction rate was studied in the range of 0-1200 rpm. As shown in Figure 7, the experimental data of the reaction kinetics follows the pseudo-first-order rate law and passes the origin point of a straight line for each experimental run. The apparent rate constants (*kapp*) were obtained from the slope of the straight lines. There was a significant increase in the apparent rate constant values from 0 to 200 rpm, but it remained at an almost constant value from 200 to 1200 rpm. This phenomenon indicated less influence of the external mass transfer resistance on the reaction beyond 200 rpm. Thus, the organic-phase reaction is obviously a rate determining step at 200-1200 rpm. All subsequent reactions were set at 1200 rpm to assess the effect of various factors on the rate of reaction.

Fig. 6. Dependence of *kobs* on stirring speed in the C-alkylation of dimedone. (Adapted from Ref. [29], by permission)

Scheme 3. *N*-alkylation of Succinimide with 1-bromo-3-phenylpropane under S-L-PTC conditions

Fig. 7. Plot of -ln(1 - X) of 1-bromo-3-phenylpropane versus time with various agitation speeds; 9.0 × 10-2 mol of succinimide, 1 g of KOH, 0.4 g of TOAB, 6.0 × 10-3 mol of 1-bromo-3-phenyl-propane, 50 mL of cyclohexanone, 0.3 g of internal standard (naphthalene), 40 °C. (Adapted from Ref. [23], by permission)

#### **2.5 S-Alkylation**

700 Mass Transfer - Advanced Aspects

almost water-free conditions (Scheme 3). For a solid-liquid phase reaction system, agitation increases the kinetic energy of the system and tends to speed up the reaction until a limiting factor is reached. After this the reaction rate is not affected by increasing stirring rates. Therefore, the effect of the agitation speed on the conversion and the reaction rate was studied in the range of 0-1200 rpm. As shown in Figure 7, the experimental data of the reaction kinetics follows the pseudo-first-order rate law and passes the origin point of a straight line for each experimental run. The apparent rate constants (*kapp*) were obtained from the slope of the straight lines. There was a significant increase in the apparent rate constant values from 0 to 200 rpm, but it remained at an almost constant value from 200 to 1200 rpm. This phenomenon indicated less influence of the external mass transfer resistance on the reaction beyond 200 rpm. Thus, the organic-phase reaction is obviously a rate determining step at 200-1200 rpm. All subsequent reactions were set at 1200 rpm to assess

Fig. 6. Dependence of *kobs* on stirring speed in the C-alkylation of dimedone. (Adapted from

N

O

H2O KBr

O

KOH, PTC Solvent, 40 0C

Scheme 3. *N*-alkylation of Succinimide with 1-bromo-3-phenylpropane under S-L-PTC

Br

the effect of various factors on the rate of reaction.

Ref. [29], by permission)

N O O H

conditions

The reaction between sodium sulfide and *n*-bromobutane to synthesize di-*n*-butyl sulfide was carried out for in an organic solvent/alkaline solution two-phase medium under phase transfer catalysis (PTC) conditions [65]. The overall reaction is presented in Scheme 4. In the two-phase reaction, mass transfer resistance is an important factor in affecting the reaction rate. In general, either the organic or the aqueous solution can be dispersed in smaller droplet size by agitating the two-phase solution, so, the contact area of two phases is increased with higher agitation speed. The flux of the two-phase mass transfer is also highly dependent on the flow condition (e.g. agitation speed). Fig. 8 shows the dependence of the apparent rate constant (*kapp,1*) on the agitation speed. For agitation speeds less than 350 rpm, both mass transfer and reaction resistance are important in determining the overall reaction rate. In this work, the reaction rate does not significantly change for agitation speeds larger than 350 rpm, and the mass transfer resistances of the active catalyst between the two phases are the same for agitation speed over 350 rpm. Hence, it is obvious that the reaction in organic phase is the rate-controlling step for agitation speed larger than 350 rpm under the standard reaction conditions. Below 50 rpm, the reaction rate is quite low because the two-phase solutions do not mix well and layering is clearly observed. Over 100 rpm, the ivory-white dispersion phase occurs. However, the phenomenon of constancy of the reaction rate constant over a certain agitation speed widely exists in PTC reactions, which are formulated based on an extraction model. Wang and Tseng [66], Jayachandran et al. [67], Park et al. [68], Wang and Wu [69] and Do and Chou [70], proposed the agitation speeds

Role of Mass Transfer in Phase Transfer Catalytic Heterogeneous Reaction Systems 703

The kinetics of dichlorocarbene addition to 1,7-octadiene have been studied under phase transfer catalytic conditions [74] using aqueous sodium hydroxide as the base and tetrabutylammonium chloride as a phase transfer catalyst (Scheme 5). In this work, the effect of agitation speed on the conversion for the reaction carried out at low alkaline concentration (30% NaOH) is shown in Fig. 9. No other byproducts were obtained during or after the reaction. The conversion is highly dependent on agitation speeds less than 800 rpm, above which the conversion is not influenced by increasing the agitation speed. The corresponding rate constant values with various agitation speeds are given in Table 5. Increasing the agitation speed leads to increase both the mass transfer coefficient and the interfacial area, thus enhancing the mass transfer rate. A similar trend was observed by Vivekanand and Balakrishnan [75] in the kinetic study of dicholorocarbene addition to indene catalyzed by triphase catalyst, where the rates were found to be independent of

+

**(min−1 M−2)** 

Cl Cl

Cl Cl

stirring speed >400 rpm.

**2.7 Esterfication** 

of diffusive mass transfer in porous catalyst.

CHCl3/ NaOH/ PTC 45 oC, 800 rpm

Cl Cl

Scheme 5. Dichlorocarbene addition to 1,7-octadiene under PTC conditions

of NaOH, 14 ml of water, 40 °C. (Adapted from Ref. [74], by permission)

**Agitation speed (rpm)** *kapp <sup>3</sup>* **× 10** 

200 0.26 400 0.88 600 1.90 700 2.58 800 3.29 100 3.41 Table 5. Effect of the agitation speed on the *kapp,3* value at low NaOH concentration: 10 mmol of 1,7-octadiene, 20 ml of chloroform, 0.2 mmol of tetrabutylammonium chloride (TBAC), 6 g

Dutta *et.al.* [76] reported kinetics of esterification of phenol derivatives *viz.,* phenol, *m*-cresol and resorcinol in alkaline solution catalyzed by polystyrene supported tri-*n*-butyl phosphonium ion under pseudo-first order conditions (Scheme 6). Kinetic results presented are interpreted in terms of three rate processes *i.e.* mass transfer of benzoyl chloride (organic substrate) to the catalyst surface, diffusion of the substrate through the polymer matrix and intrinsic reactivity at the active sites. The reaction engineering aspects have been addressed from experimentally observed rate determining phenomena as complimented by the theory

The order of reactivity of different phenol derivatives: resorcinol< *m*-cresol< phenol. Apparent rate constants were found to increase up-to 800-1000 rpm (stirring speed) for different phenols, beyond which the *kapp* values were found to be remain constant. They reported that catalysts with particle size lower than 70μm do not enhance the rate. This is

from 200 to 800 rpm. This threshold value changes with changes in the reaction parameters, e.g. the two-phase surface tension will be changed using different organic solvents or adding cationic surfactants, so the maximum two-phase mass transfer rate will be changed under different agitation speeds.

2RBr + 2Na2S PTC R2S <sup>+</sup> 2NaBr

Scheme 4. Thioether synthesis under phase-transfer catalysis conditions

Fig. 8. Effect of the agitation speed on the apparent rate constant (*kapp,1*) in the organic phase; 7 g of sodium sulfide, 10 ml of water, 0.15 mmol of TBAB, 4 mmol of n-bromobutane, 40 ml of n-hexane, 40 °C. (Adapted from Ref. [65], by permission)

#### **2.6 Dichlorocyclopropanation**

Mass transfer between two phases in a phase-transfer catalysis system is important in affecting the conversion or the reaction rate. From the point of kinetics, changing the agitation speed can influence both the mass transfer rate, which relates to the mass transfer coefficient and the interfacial area between two phases, and the reaction rate. Increasing the agitation speed leads to increase both the mass transfer coefficient and the interfacial area, thus enhancing the mass transfer rate. The effects of varying stirring on the rate constants of the dicholorocarbene addition reactions were documented in the literature [40, 71-73].

The kinetics of dichlorocarbene addition to 1,7-octadiene have been studied under phase transfer catalytic conditions [74] using aqueous sodium hydroxide as the base and tetrabutylammonium chloride as a phase transfer catalyst (Scheme 5). In this work, the effect of agitation speed on the conversion for the reaction carried out at low alkaline concentration (30% NaOH) is shown in Fig. 9. No other byproducts were obtained during or after the reaction. The conversion is highly dependent on agitation speeds less than 800 rpm, above which the conversion is not influenced by increasing the agitation speed. The corresponding rate constant values with various agitation speeds are given in Table 5. Increasing the agitation speed leads to increase both the mass transfer coefficient and the interfacial area, thus enhancing the mass transfer rate. A similar trend was observed by Vivekanand and Balakrishnan [75] in the kinetic study of dicholorocarbene addition to indene catalyzed by triphase catalyst, where the rates were found to be independent of stirring speed >400 rpm.

Scheme 5. Dichlorocarbene addition to 1,7-octadiene under PTC conditions


Table 5. Effect of the agitation speed on the *kapp,3* value at low NaOH concentration: 10 mmol of 1,7-octadiene, 20 ml of chloroform, 0.2 mmol of tetrabutylammonium chloride (TBAC), 6 g of NaOH, 14 ml of water, 40 °C. (Adapted from Ref. [74], by permission)

### **2.7 Esterfication**

702 Mass Transfer - Advanced Aspects

from 200 to 800 rpm. This threshold value changes with changes in the reaction parameters, e.g. the two-phase surface tension will be changed using different organic solvents or adding cationic surfactants, so the maximum two-phase mass transfer rate will be changed

2RBr + 2Na2S PTC R2S <sup>+</sup> 2NaBr

Agitation speed (rpm) 0 200 400 600 800 1000

Fig. 8. Effect of the agitation speed on the apparent rate constant (*kapp,1*) in the organic phase; 7 g of sodium sulfide, 10 ml of water, 0.15 mmol of TBAB, 4 mmol of n-bromobutane, 40 ml

Mass transfer between two phases in a phase-transfer catalysis system is important in affecting the conversion or the reaction rate. From the point of kinetics, changing the agitation speed can influence both the mass transfer rate, which relates to the mass transfer coefficient and the interfacial area between two phases, and the reaction rate. Increasing the agitation speed leads to increase both the mass transfer coefficient and the interfacial area, thus enhancing the mass transfer rate. The effects of varying stirring on the rate constants of the dicholorocarbene addition reactions were documented in the literature [40, 71-73].

Scheme 4. Thioether synthesis under phase-transfer catalysis conditions

under different agitation speeds.

K app,1

**2.6 Dichlorocyclopropanation** 

×10 (min )

3

 -1 12

10

8

6

4

2

0

of n-hexane, 40 °C. (Adapted from Ref. [65], by permission)

Dutta *et.al.* [76] reported kinetics of esterification of phenol derivatives *viz.,* phenol, *m*-cresol and resorcinol in alkaline solution catalyzed by polystyrene supported tri-*n*-butyl phosphonium ion under pseudo-first order conditions (Scheme 6). Kinetic results presented are interpreted in terms of three rate processes *i.e.* mass transfer of benzoyl chloride (organic substrate) to the catalyst surface, diffusion of the substrate through the polymer matrix and intrinsic reactivity at the active sites. The reaction engineering aspects have been addressed from experimentally observed rate determining phenomena as complimented by the theory of diffusive mass transfer in porous catalyst.

The order of reactivity of different phenol derivatives: resorcinol< *m*-cresol< phenol. Apparent rate constants were found to increase up-to 800-1000 rpm (stirring speed) for different phenols, beyond which the *kapp* values were found to be remain constant. They reported that catalysts with particle size lower than 70μm do not enhance the rate. This is

Role of Mass Transfer in Phase Transfer Catalytic Heterogeneous Reaction Systems 705

coefficient increases with the increasing agitation rate indicated the dependence of the mass

Triphase Catalyst

Conventional technologies for multiphase organic reactions were largely uneconomical and polluting and hence were commercially not feasible. In recent years, several new techniques have emerged that use homogeneous or heterogeneous catalysts such as phase transfer catalysts, supported metal catalysts, biocatalysts etc. Among various types of catalysts, phase transfer catalysts have attracted more and more attention. It facilitates interphase transfer of species, making reactions between reagents in two immiscible phases

Many organic synthetic applications based on PTC have shown great success. The present chapter has hence concentrated on the PTC reactions, *viz.,* alkylation reactions, esterfication reactions, dichlorocarbene addition reactions etc., using both soluble and immobilized forms of the catalyst. By its very nature, PTC involves interphase transport of species, neglecting which can grossly over predict the conversion of a PTC mediated reaction. Hence, greater emphasis has been given to present the role of mass transfer in PTC-assisted reactions. Nevertheless, there are definitely numerous catalytic reactions still waiting to be discovered and hence, opportunity for major discovery will remain vibrant for a very long time indeed. The new designs for microwaves and ultrasound assisted PTC reactions and the relevant mass transfer data is most essential to understand the design and scale-up of these emerging technologies in industries. It is hoped that this chapter will spur further research in this area, whose applications in the manufacture of organic intermediates and fine chemicals seems

We gratefully acknowledge support of this work by the National Science Council, Taiwan (NSC), under several grants. Further, we would like thank numerous students and

postdoctoral scientists who have worked on these projects.

A = Mass-transfer area between organic and aqueous phase, cm2/cm3

O

O

R

transfer coefficient on the agitation rate.

OH O Cl

R = H, CH3, OH

**3. Conclusion** 

possible.

almost unlimited.

**5. Nomenclature** 

**4. Acknowledgments** 

Stirring <sup>R</sup>

Scheme 6. Esterfication of substituted phenols under PTC conditions

attributed to low mass transfer of reactants from the bulk phase to the particle surface and hence the reaction rate is reduced. However the reaction rate is better than the uncatalyzed reaction. In presence of highly active catalyst, mass transfer from the bulk phase to the surface of the catalyst particle can be rate controlling step. They reported that the mass transfer of benzoyl chloride from the bulk organic phase to the surface of the catalysts depends on the contact between the polymer particles and organic droplets, both of which are suspended in a continuous phase of aqueous sodium phenolate. Authors interpreted the kinetic results in terms of three aspects *viz.,* i) mass transfer of benzoyl chloride to the catalyst surface, ii) diffusion of benzoyl chloride through polymer matrix, and iii) intrinsic reactivity at the active sites.

Fig. 9. Effect of the agitation speed on the conversion of 1,7-octadiene at low alkaline concentration (30% NaOH): 10 mmol of 1,7-octadiene, 20 ml of chloroform, 0.2 mmol of tetrabutylammonium chloride (TBAC), 6 g of NaOH, 14 ml of water, 40 °C. (Adapted from Ref. [74], by permission)

Esterifcation of benzyl chloride with sodium acetate to form benzyl acetate and sodium chloride were carried out under tri-phase conditions using polymer supported

tributylmethylammonium chloride as the phase transfer catalyst [77]. The investigation focused on the determination of external mass transfer coefficient from the liquid bulk phases to the surface of the catalyst in tri-phase catalytic systems. Special emphasis was placed on the equipment (rotating disk contactor, RDC) which has been conceived and designed for this purpose. Determination of mass transfer coefficient involves an analysis of the various regimes of solid-liquid systems with the solid not soluble in the liquid phase.

Esterfication was found to be mass transfer controlled at low agitation speeds and it was found to be characterized by considerable non-catalytic reaction and effects due to dispersion associated with the catalyst. Nevertheless, it was possible to determine the external mass transfer coefficient as a function of the bulk agitation speed. The mass transfer coefficient increases with the increasing agitation rate indicated the dependence of the mass transfer coefficient on the agitation rate.

Scheme 6. Esterfication of substituted phenols under PTC conditions
