Organic synthesis in suppercritical carbon dioxide

Abstract

Many industrially important synthesis reactions are carried out in liquid solvents such as aromatic compounds, chlorinated hydrocarbons, and other organic liquids which pose environmental and health hazards either because of their toxicity or their persistence in the environment. Hence proper disposal of these solvents and the prevention of accidental releases or routine emissions cause serious difficulties and costs for the industries who use them. An approach to mitigating these problems is to use alternative solvents that are environmentally benign or that can be completely recycled in a closed-loop process. One such alternative solvent is supercritical carbon dioxide. Although supercritical carbon dioxide is used in many industrial extraction and chromatography processes it is not widely used as a reaction medium and its effects on chemical reactions are not well understood. The goals of this research were to gain a better understanding as to the effect of supercritical carbon dioxide through a systematic investigation of solvent conditions on the rates and selectivities of several model organic synthesis reactions. In addition, the use of environmentally benign catalysts/promoters in gaseous and supercritical carbon dioxide as well as developing chemical pathways in which carbon dioxide can act as a solvent as well as a reactant were explored to expand the possible industrial applications. In the pursuit of these goals, new reactors, feed and sampling procedures, as well as new chemical pathways were explored. Specifically, the bimolecular rate constants of the Diets-Alder reaction of ethyl acrylate and cyclopentadiene were measured in supercritical carbon dioxide from 38 to 88 °C and pressures from 80 to 210 bar. At constant temperature, the rate increased with pressure or density and was most dramatic near the critical point of carbon dioxide. A traditional Arrhenius expression was used to correlate the kinetic data at a constant system density. All of the rate constant data were normalized to the rate constant at the same temperature and at a fixed density of 0.5 g/cm3. These normalized rate constants over a range of temperatures then collapsed on a single line as a function of density. Rates could be predicted using a bimolecular Arrhenius expression with the pre-exponential term having a linear dependence on density. Theoretically, a rigorous transition state theory rate constant was derived and used to gain a better understanding of the non-ideal solvent-reactant-product interactions which could influence the rate. Effects of pressure/density and temperature on the regio- and stereo- selectivity of several Diels-Alder reactions were explored. Regioselectivity did not correlate well with density changes; however, stereoselectivity did. As pressure was increased, the endo isomer always increased in the supercritical region. The stereoselectivity changes were modeled using temperature and density as the model inputs. Again, the rigorous transition state theory rate constant was used to explain the observed selectivity changes. Phase behavior played an important role in these investigations, sometimes influencing selectivity. The design and construction of reactors with a sapphire window allowed for visual access into the reaction environment to monitor phase behavior. Silica was shown to increase the rate and selectivity of several Diels-Alder reactions in carbon dioxide. Pressure/density effects were explored using the reaction of methyl vinyl ketone and penta-1,3-diene. Pressure did not affect the selectivity; however, it had a large effect on the yield of the reaction. This was discovered to be caused by the change in phase partitioning of the reactants between the fluid phase and the solid surface as pressure was changed. Adsorption isotherms at various pressures and temperatures were found. Because of the non-ideal system, the thermodynamic effect of temperature on the adsorption equilibrium needed to be derived. The effect of temperature on the adsorption was found at constant pressure. Although an enthalpy of adsorption could be determined, the presence of non-ideal phase behavior complicates its interpretation. In general, the adsorption enthalpy consists of partial molar enthalpies of both species (reactant and carbon dioxide) on/in both phases (solid/fluid). At constant density, the effect of temperature allows for the direct calculation of the entropy of adsorption. This term is affected by the partial molar entropies of both species on/in both phases. Three different carboxylation reactions were investigated in supercritical carbon dioxide. The Kolbe-Schmitt reaction (direct carboxylation of a phenolate salt) was found to proceed at high yields in supercritical carbon dioxide. Attempts at lowering the temperature of reaction by using cosolvents was not successful. Temperature and pressure had minimal effect on the selectivity of the reaction. Two other carboxylation reactions were examined. In the first study, the homogeneous catalyzed caboxylation of an allylsilane was performed in supercritical carbon dioxide. Pressure did not appear to affect the reaction; however, there was a narrow temperature range which allowed the reaction to proceed. At best, yields were only 15%. The final reaction studied was the catalyzed (Lewis acid) carboxylation of an alkene by carbon dioxide. Unfortunately it did not proceed in supercritical carbon dioxide to any measurable extent at temperatures of 40 to 350 °C with and without the presence of various catalysts.