Gas-expanded liquids (GXL) are a new and benign class of liquid solvents that are intermediate in physical properties between normal liquids and supercritical fluids and therefore may offer advantages in separations, reactions, and advanced materials. Phase-transfer catalysis (PTC) is a powerful tool in chemistry that facilitates interaction and reaction between two or more species present in immiscible phases and offers the ability to eliminate the use of frequently expensive, environmentally undesirable, and difficult to remove polar, aprotic solvents. The work presented here seeks to further characterize the transport properties of GXLs and apply these new solvents to PTC systems, which could result in both greener chemistry and improved process economics. The transport properties of GXL are characterized by the measurement of diffusivities by the Taylor-Aris dispersion method and calculation of solvent viscosity based on those measurements. The measurement of these bulk properties is part of a larger effort to probe the effect of changes in the local structure surrounding a solute on the solution behavior. The two technologies of PTC and GXL are combined when the distribution of a phase-transfer catalyst between GXL and aqueous phases is measured and compared to changes in the kinetics of a reaction performed in the same system. The results show that increased reaction rates and more efficient catalyst recovery are possible with GXL solvents.

Developing environmentally sustainable processes are essential to improving the quality of life for future generations. In addition to reducing our impact on the environment, we must design processes to be both economical and safe. A large component of any chemical process is the solvents used to dissolve the reactants and extract the products. The research presented here focuses on coupling efficient homogeneous reactions with simple heterogeneous separations using propane-organic-aqueous tunable solvent systems. Our tunable solvents undergo a phase separation upon application of propane pressure to a fully miscible mixture of water and an organic solvent. The propane based tunable systems detailed here eliminate carbonic acid formation and reduce productphase contamination when compared with the equivalent CO2 based solvent systems previously studied. Additionally, we eliminate the need to use buffers and thus solids handling equipment is not needed.

We develop, characterize, and apply novel solvent systems for enhanced separations. The field of separations has long been explored by chemical engineers. One way to optimize separations is through solvent manipulation. Through molecular design, smart solvents can be created which accomplish this task. Smart solvents undergo step or gradual changes in properties when activated by a stimulus. These property changes enable unique chemistry and separations. This thesis explores the application of two different types of smart solvents: switchable and tunable solvents. First we show that a neutral liquid can react with carbon dioxide and be switched into an ionic liquid which can then be thermally reversed back to its molecular form. Each form that the solvent takes has unique properties that can be structurally tuned to span a large range. We also look at a tunable solvent system based on polyethylene glycol/dioxane that is initially homogeneous, but induced to a heterogeneous system through carbon dioxide pressurization. Finally, we look at the advantage of using carbon dioxide as a co-solvent that is easily removed post-reaction for the grafting of silanes onto polyolefin backbones.

The research projects presented in this thesis are mainly focused toward green chemistry and engineering: developing innovative strategies to minimize waste, improve process efficiency and reduce energy consumption. Specifically, the work was centered on the design and applications of green solvents and processes for the sustainable production of pharmaceuticals. The first project was focused on the use of CO₂ to enhance Suzuki coupling reactions of substrates containing unprotected primary amines. This work established that exceptionally challenging substrates like halogenated amino pyridines (i.e. 4-amino-2-bromopyridine and 4-amino-2-chloropyridine) are suitable substrates for Suzuki coupling reactions under standard conditions using CO₂ pressures, without the need for protection/deprotection steps which are traditionally considered to be necessary for these reactions to proceed cleanly. The second project explored the use of water at elevated temperatures (WET) for the sustainable and selective removal of protecting groups. The favorable changes that occur in the physiochemical properties (i.e. density, dielectric constant and ionization constant) of water at elevated temperatures and pressures make it an attractive solvent for the development of sustainable, environmentally green processes for the removal of protecting groups. The water-mediated selective removal of protecting groups such as N-Boc, N-Acetyl and O-Acetyl from a range of organic model compounds was successfully achieved by tuning the temperature (125 to 275°C) or properties of water. The third project investigated the use of Organic-Aqueous Tunable Solvents (OATS) for the rhodium catalyzed hydroformylation of p-methylstyrene. This enables the reactions to be carried out efficiently under homogeneous conditions, followed by a carbon dioxide (CO₂) induced heterogeneous separation. Modest pressures of CO₂ induced the aqueous-rich phase (containing the catalyst) to separate from the organic-rich phase (containing the reactant), thus enabled an easy separation and recycling of catalyst. The use of Al(OtBu)₃ as a potent catalyst toward continuous Meerwein-Ponndorf-Verley (MPV) reductions was established in the fourth project. The MPV reduction of model compounds like benzaldehyde and acetophenone to their corresponding alcohols was investigated in continuous mode as a function of temperature and catalyst loading. These results established a roadmap for the pharmaceutical industry to document the implementation of continuous flow processes in their manufacturing operations.

The work in this thesis couples reactions with separations through the use of switchable and tunable solvents. Tunable solvents are mixed solvents which can be easily altered to afford conditions optimal for reaction or separation. Switchable solvents are solvents that can be switched when desired to alter their properties affording conditions suitable for separation. Other studies are of the reaction of CO2 with the amidine base DBU, and an NMR study of solvent-to-solute nuclear Overhauser effects. These examples constitute a marriage of reaction environment with separation environment, significantly, to the benefit of both.

The focus of this research was to improve the sustainability of various processes by employing tunable solvents, switchable solvents, and catalysis. In Chapter 2, we report applications of tunable solvents to metal and enzyme catalyzed reactions of hydrophobic substrates. Tunable solvents are defined as solvent that change properties rapidly but continuously upon the application of an external physical stimulus and we utilize these solvents to couple homogeneous reactions with heterogeneous separations. We developed organic-aqueous tunable solvents that utilize propane for efficient phase separation at moderate pressures around 1 MPa; for example the water contents in the propane-expanded THF is 3 wt% at 0.8MPa at 30°C. Also, we extended the use of CO2-organic-aqueous tunable solvents to a pharmaceutically-relevant reaction--the hydroformylation of p-methylstyrene. The homogeneous reactions provide fast rates with excellent yields. At 60°C, the reaction reaches completion after 180 minutes with 95% branched aldehyde yield. The CO2-induced heterogeneous separation of the product from the catalyst provides an efficient and simple way to remove 99% of the product, to retain 99.9% of catalyst, and to recycle the Rh-TPPMS catalyst for five consecutive reactions. In chapter 3, we investigated the use of reversible ionic liquids (RevILs) for synthesis of nanoparticles. RevILs are formed by the reversible reaction of compounds with basic nitrogen functionalities (molecular liquid) with CO2 at ambient pressure to form a liquid salt (ionic liquid). We demonstrated that RevILs form microemulsions that can be switched-on by bubbling CO2 and switched-off by heating. These microemulsions solubilize ionic compounds such as chloroauric acid. We utilized these microemulsions as a template for controlled synthesis of gold nanoparticles. With 2-component RevILs, [TMBGH]+[O2COCH3]-/N-propyl-octylsulfonamide/hexane were used to form particles in the size range of 6-20 nm with an average particles size of 11.4±3.3. With 1-component RevILs, (3-aminopropyl)-tripropylsilane was used to prepare semi-spherical gold particles with an average size of about 20nm. The 1-component RevILs systems provide a simpler method to form microemulsions when compared to the 2-componenet RevILs systems since they eliminate the need for alcohols and surfactants. In chapter 4, we developed a catalyst that efficiently decomposes hydrazine to selectively produce ammonia. This enables the use of the chemical propulsion hydrazine for electric propulsion as well. We prepared nickel, copper, cobalt, ruthenium, rhodium, and iridium nanoparticles that were supported on silica and we tested these silica-supported metals for the decomposition of hydrazine. To study the catalytic activity, we designed and constructed a continuous flow reactor. The results show that nano-nickel supported on silica is the most active and selective catalyst with 100% conversion of hydrazine and 94±3% yield of ammonia.