Reactions in Supercritical Media

Supercritical fluids have many features that render their use attractive in synthetic chemistry and separations. Their tunable physical properties allow reactions to be carried out under a variety of conditions and, in some cases, the selectivities and rates of reactions may be altered. The list of reactions that have been carried out in SCFs and compared with those in conventional solvents is continually growing. 

There are now examples where products and selectivities that cannot be achieved in conventional solvents can be realized by the use of a SCF. However, as noted above, the high running costs which result from carrying out a process at elevated temperatures and pressure may well preclude their use for many reactions. 

Jessop P. G. and Leitner W. Chemical Synthesis using Supercritical Fluids, Wiley-VCH, Weinheim, 1999. 

Lide D. R. and Frederiks H. P. R. CRC Handbook of Chemistry and Physics, 75th Edition, CRC Press, Boca Raton, 1994. 

(a) Clifford A. A. Fundamentals of Supercritical Fluids, Oxford University Press, Oxford, 1998 (b) Oakes R. S., Clifford A. A. and Rayner C. M. Perkin Trans. 1, 2001, 917 (c) Ed. Jessop P. G. and Leitner W. (eds) Chemical Synthesis using Supercritical Fluids, Wiley-VCH, Weinheim, 1999, and references therein. 

As a consequence of the very low viscosity, reaction rates can be very high in supercritical media. This was recently demonstrated for hydrogenation of TGs in supercritical propane (Harrod and Moller, 1996). The reaction took place in a small cell, and reaction rates up to 1000 times higher than those obtained with traditional techniques were reported. 

SFE is a very promising method for sample preparation and it has already been employed extensively in connection with lipid analysis, where it can be a substitute for traditional Soxhlet extraction. In addition, there is considerable potential for further development of preparative SFC. 

Whilst it is obviously valuable to measure the solubility of reagents in the SCF, it is important to be aware that the solubility in a multicomponent system can be very different from that in the fluid alone. It is also important to note that the addition of reagents and catalysts can have a profound effect on the critical parameters of the mixture. Indeed, at high concentrations of reactants, the mole fraction of C02 is necessarily lower and it may not be possible to achieve a supercritical phase at the temperature of interest. Increases in pressure (i.e. further additions of C02) could yield a single liquid phase (which would have a much lower compressibility than scC02). For example, the Diels-Alder reaction (see Chapter 7) between 2-methyl-1,3-butadiene and maleic anydride has been carried out a pressure of 74.5 bar and a temperature of 50 °C, assuming that this would be under supercritical conditions as it would if it were pure C02. However, the critical parameters calculated for this system are a pressure of 77.4bar and a temperature of 123.2 °C, far in excess of those used [41]. 

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Reactions in supercritical media utilize high pressures. Therefore, the effect of pressure on reaction equilibrium as well as reaction rate plays an important role in supercritical phase reactions. Supercritical fluids that exhibit very high negative activation volumes for certain reactions will improve the rate and equilibrium conversion of the reaction. 

Reacting gases that can be evaporated may be in excess if they do not condense to liquid phases, but reactions in supercritical media are clearly not the subject of solvent-free chemistry and deserve their own treatment. For practical reasons, this book does not deal with homogeneous or contact-catalyzed gas-phase reactions. Furthermore, protonations, solvations, simple complexations, ra-cemizations and other stereoisomerizations are not covered, in order to concentrate on more complex chemical conversions. This strategy allowed the presentation of diverse reaction types and techniques, including those that proceed only in the absence of liquid phases, in one convenient volume. 

Continuous, selective hydroformylation in supercritical CO2 using (acac)Rh(CO)2 immobilized on silica as catalyst shows certain advantages. A version of asymmetric hydroformylation in this medium has also been reported,. (Subcritical CO2 gas accelerates solventless synthesis involving solid reactants, including hydrogenation and hydroformylation.) The regioselective and enantioselective nickel-catalyzed hydrovinylation of styrenes in supercritical CO2 make 3-arylpropenes available in an optically active form. " Improvement in the performance of the Pauson-Khand reaction in supercritical media... 

This result, together with the accuracy of thermodynamical parameters previously measured, confirms that the supercritical calorimeter is operating correctly and validates the equipment for calorimetric evaluation of reactions in supercritical media. 

In conventional polymerization processes in organic solvents, it is possible to follow the reaction rate by correlating the decrease in pressure of a supply of gaseous monomer to the conversion. Heller describes a method in which the decrease in pressure is correlated to the reaction rate with a virial equation of state [28]. A similar method can be used for reactions in supercritical media, which are often subject to a pressure change upon reaction. In this study, a model was developed to determine the reaction rate indirectly based on the measured pressure during polymerization and based on a description of the phase behavior of the polymer and supercritical fluid phase [9, 29]. 

Pressure Effects. Reactions in supercritical media typically involve elevated pressures that could have either an enhancing or inhibiting effect on rate and equilibrium constants. Based on transition-state theory, the pressure dependence on the rate constant is given by the following equation ... 

NMR spectroscopy is routinely used in today s organic synthesis laboratories to identify and structurally characterize reaction products. Yet despite the enormous structural information content of NMR and the availability of a variety of high-pressure NMR techniques (3-13), it is little used for studying in situ chemical reactions and solvent effects on chemical reactions in supercritical media. 

MM Hoffmann, MS Conradi. Hydrogen exchange reactions in supercritical media monitored by in situ NMR. J Supercrit Fluids 14 31-40, 1998. 

A continuous process was performed by van Eijs et al. [69] and Marty et al. [54], Substrates can be continuously injected into the SCCO2 flow by a high-performance liquid chromatography (HPLC) pump. The substrate concentration is known, an adjustment to a fixed value is possible. In this case the CO2 was not recycled. They also developed a continuous process with recycling of CO2 and post reactional fractionation (Fig. 2) [2], Table 3 shows studies of important parameters for reactivity and productivity of enzymatic reactions in supercritical media. Furthermore, some authors compare supercritical media and conventional organic solvents ... 

Table 3 Parameters for Reactivity and Productivity of Enzymatic Reactions in Supercritical Media...

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