Low molecular weight polyethylene glycol (PEG 300), polypropylene glycol (PPG 425), and their aqueous solutions are investigated for use as novel, nonvolatile, environmentally friendly reaction solvents. The kinetics and selectivities of a S(N)1 and a Diels-Alder reaction (reactions commonly used in pharmaceutical synthesis) in the polyglycol-H2O solutions are reported. Reaction rate constants and product selectivities in the polyglycol-H2O solvents were comparable to those observed in the traditional organic solvents used with these reactions. Gibbs free energy calculations show that the reactants and reaction transition states for the S(N)1 and Diels-Alder reactions are stabilized in the presence of the polyglycol-H2O solvents. (C) 2004 American Institute of Chemical Engineers.