B. Potential Advantages of SCF Reaction Processes

tion application by tuning the various density-dependent fluid properties (60).

As an example, by pressure-tuning the reaction mixture, Kim and Johnston (61)

demonstrated continuous control of the selectivity of two competing parallel

Diels–Alder additions of methyl acrylate and cyclopentadiene to produce both

the endo and exo products.

Solubility effects can influence reaction processes in several ways. For

example, the solubilities of various reactants, products, and, in some cases,

homogeneous catalysts can be manipulated to process advantage (e.g., homogenizing a previously heterogeneous reaction mixture). The enhanced solubility

of catalyst-fouling components has been exploited to minimize heterogeneous

catalyst deactivation through extraction of these fouling products or contaminants and prevention of subsequent coking (62). In addition, solubility effects

can potentially be utilized in an SCF-based process through integration of the

reaction step with product isolation to synthesize a novel reactive separation

process.

Since gaseous reactants are completely miscible with SCFs, their concentrations in SCF reaction media are significantly higher than that obtainable in

conventional liquid solvents, even at appreciable pressures (63). These higher

reactant concentrations in SCF media combined with increased component diffusivities and relatively low system viscosities (see Table 1) can result in mass

transfer rates that are appreciably higher than in liquid solvents. This can potentially shift a chemical reaction rate from mass transfer control to kinetic

control in the reactor. For example, Noyori and coworkers (64) reported the

hydrogenation of scCO2 to formic acid at rates of up to 18 times that in liquid

tetrahydrofuran, which they attribute to the enhanced mass transfer characteristics and high hydrogen miscibility afforded by the SCF mixture. The solubility

of gaseous reactants in liquid solvents can also be enhanced by a volume expansion of the solvent with a dense SCF, which likewise results in increased mass

transfer rates (65). Improved mass transport can also result in enhanced removal

of residual solvents (26).

A key density-dependent property of SCFs that is sometimes overlooked

is the heat capacity, which is relatively high in the vicinity of the critical point

compared with gases (42,66). This high heat capacity produces effective heat

transfer relative to gas-phase reactions. Thus, highly exothermic reactions such

as hydrogenations can be conducted in SCF media with accurate temperature

control (67).

As will be described below, both pressure and temperature effects can be

used to influence chemical transformations. For example, reaction selectivity can

be influenced indirectly through a pressure-dependent dielectric constant for a

polar SCF solvent (68), and equilibrium constants can be shifted to favor desired

products. Combining this manipulation of reaction characteristics through pressure effects with the use of solvents having moderate critical temperatures can



Copyright 2002 by Marcel Dekker. All Rights Reserved.



be used for economical processing of temperature-sensitive materials at milder

reaction conditions (26). Viscosity effects can be exploited to tune reaction selectivity. For example, Aida and Squires (69) have demonstrated a pronounced

pressure dependence on the photoisomerization of trans-stilbene in scCO2 at

40◦ C, which they attribute to significant changes in the solvent viscosity over

the pressure range investigated.

A reason often cited for considering SCF-mediated reaction processes is

the potential for utilizing a reaction solvent that exhibits improved safety, health,

and environmental impact relative to typical organic solvents. Carbon dioxide,

in particular, is generally considered environmentally benign, nontoxic, nonflammable, and inexpensive, and it is suitable for use as an SCF solvent at

relatively moderate temperatures. However, as illustrated in Table 2, there are a

variety of other practical SCF solvents that may have better solubility characteristics than CO2 as well as beneficial impact relative to conventional organic

solvents.

C. Phase Behavior

The dramatic property changes that occur in the vicinity of the critical point

that result in these various potential advantages of conducting chemical reactions in SCF media have been illustrated for the simple case of a pure fluid in

Figures 2–4. These property variations as well as the underlying mixture critical

curve behavior are much more complex for the multicomponent systems that will

be encountered in all practical applications for conducting SCF-mediated chemical transformations. One must know the location of phase boundaries and the

magnitude of these property variations to fully exploit these potential advantages

as well as to robustly control operating processes in the vicinity of a critical point

where density fluctuations are significant (7,33,70–73). Thus, the importance of

accurate measurement and modeling of solubility data and the corresponding

phase behavior for the reactant–product–solvent systems is fundamental to the

accurate interpretation of experimental reaction rate and selectivity data as well

as the reliable scaling to commercial processes. Presentation of the appropriate

phase equilibrium thermodynamics and calculational techniques for correlating

experimental measurements and estimating multicomponent phase behavior is

beyond the scope of this chapter, but a number of excellent sources are available

in the literature for reference (e.g., see Refs. 40,70,74–77).

Utilization of SCF media for conducting chemical reactions results in

several unique phase behavior features and challenges. A number of these are

summarized here to better understand the phase behavior implications in the applications reviewed below. Some of these extend directly from the above discussion regarding potential advantages of using SCF media for conducting chemical



Copyright 2002 by Marcel Dekker. All Rights Reserved.



reactions. For example, by conducting a reaction in the SCF-phase regime, all

of the reactants can exist in a single homogeneous phase. This eliminates interfacial mass transfer resistances that would otherwise result in diffusional control

in carrying out a specific reaction. For homogeneous catalysis applications, the

catalyst can likewise exist in this same homogeneous phase with corresponding reductions of mass transfer resistances. Alternatively, in some applications,

an SCF phase can be used to expand a separate liquid reaction phase and still

provide substantial benefit in improved reactant mass transfer rates (65). Since

the critical point of a multicomponent mixture is composition dependent, the

critical point of a reaction mixture will change with the extent of reaction, and

thus, with time in a batch reactor or with location in a continuous fixed-bed

reactor (33). As illustrated previously, the various density-dependent physical

properties can be manipulated with density changes for an SCF, resulting in

a corresponding effect on reaction rates and selectivity (e.g., 68,78–80). For

example, Combes et al. (81) have demonstrated control of both regio- and stereoselectivity through tuning of SCF solvation effects. Thus, manipulation of the

phase behavior can be used to optimize the effect of these various parameters on

specific reaction applications. The phase behavior of SCF systems can also be

manipulated to control the number and composition of coexisting phases (79),

thus controlling both reaction effects as well as the separation of products or

homogeneous catalysts from the reaction mixture. Finally, the addition of cosolvents can be effectively utilized to exploit specific solute interactions such as

enhancing solute solubilities (e.g., 70) and influencing reaction selectivities (79)

and equilibria (82).

D. Thermodynamic Pressure Effects on Reaction Rates

Pressure is a fundamental physical property that affects various thermodynamic

and kinetic parameters. Pressure dependence studies of a process reveal information about the volume profile of a process in much the same way as temperature

dependence studies illuminate the energetics of the process (83). Since chemical

transformations in SCF media require relatively high operating pressures, pressure effects on chemical equilibria and rates of reactions must be considered in

evaluating SCF reaction processes (83–85). The most pronounced effect of pressure on reactions in the SCF region has been attributed to the thermodynamic

pressure effect on the reaction rate constant (86), and control of this pressure

dependency has been cited as one means of selecting between parallel reaction

pathways (87). This pressure effect can be conveniently evaluated within the

thermodynamic framework provided by transition state theory, which has often been applied to reactions in solutions (31,84,88–90). This theory assumes

a true chemical equilibrium between the reactants and an activated transition



Copyright 2002 by Marcel Dekker. All Rights Reserved.



state species that has the required energy and conformation corresponding to

the internal energy barrier for chemical reaction. This transition state complex

then proceeds directly to products, and the rate of the chemical reaction is governed by the rate constant for this decomposition from the activated state. This

is illustrated for a bimolecular reaction between reactants A and B forming the

transition state M‡ by

A+B



M‡ → products



The pressure dependence of the reaction rate constant is given by the following

relation in terms of partial molar volumes and isothermal compressibility (90):

∂ ln kbm

∂P



=−



ν‡

− kT

RT



where kbm = bimolecular rate constant (mol/L-min), ν‡ = νM‡ − νA − νB =

activation volume (the difference between the partial molar volumes of the transition state species and that of the reactants), νi = partial molar volume of

component i at reaction conditions, kT = mixture isothermal compressibility,

and R = universal gas constant. Note that the isothermal compressibility term

in the above equation accounts for changes in the reactant concentrations with

pressure. This term is not included if the rate constant is expressed in pressureindependent units, such as mole fraction or molality (84,91). A more general

expression for the pressure effect on the rate constant that accounts for the

number of reactant species is given by

∂ ln k

∂P



=−



ν‡

+ (1 − n)kT

RT



where n is defined as the sum of the stoichiometric coefficients of the reactants

(78,91).

Note from these expressions that a chemical reaction is accelerated by

pressure if its activation volume is negative. This is generally the case for most

addition reactions, and as an example, this effect has been exploited advantageously to accelerate cycloaddition reactions by pressure (92). In addition,

dissociation reactions can be favored by pressure if charged species are formed

through electrostriction effects. This causes an ordering of charged (ions) and

uncharged (e.g., solvent) species, which results in a significant decrease in molar volume (93). The partial molar volumes and isothermal compressibility of

the reaction mixture can be estimated from an equation of state. Brennecke

and coworkers (90,94) present the appropriate thermodynamic correlations to

estimate these values, and they have applied these calculations using the Peng–

Robinson equation of state (95).



Copyright 2002 by Marcel Dekker. All Rights Reserved.