| In recent years, the demand for safe, environmentally friendly solvents has grown, spurred by EPA and OSHA regulations. In this research, low molecular weight polypropylene glycol (PPG 425), polyethylene glycol (PEG 300), and their aqueous solutions are investigated for use as novel, safe, environmentally friendly solvents with particular application in the pharmaceutical industry. Not only are these solvents relatively non-toxic, they are also non-volatile, which eliminates the possibility of fugitive gaseous emissions and allows for the use of high temperatures without pressure buildup. In addition, many organic compounds have been found to be soluble in these polyglycol solutions; thus, they could be used as replacement solvents in various chemical processes.; One use of the solvents would be as the medium for conducting chemical reactions. Three classes of organic reactions (SN1, SN2 and Diels-Alder) relevant to pharmaceutical synthesis have been investigated. The effect of the polyglycol-H2O solvents on rate constants, overall reaction rates, and product selectivities were obtained and compared to those obtained in traditional organic solvents. For the SN1 and Diels-Alder reactions, the rate constants and reactant solubilities in the polyglycol solvents were higher or comparable to those obtained in the frequently used organic solvents. For the SN2 reaction, reactant solubilities were high in the polyglycol-H2O solutions, but rate constants were about an order of magnitude lower than those obtained in the traditional organic solvents. Product selectivities/stereoselectivities were similar to those obtained in traditional organic solvents. From the data, rate constants were correlated using solvent molecular interaction parameters. Furthermore, the Gibbs free energy of the reactants and transition states were calculated in the various solvents. From the Gibbs free energy results, it was found that the reaction transition states were generally stabilized in the polyglycol-H 2O solutions. Overall, this study shows that polyglycol solutions offer promise as benign, environmentally friendly reaction solvents for organic synthesis. |
