Glycerol-based solvents in organic synthesis ABSTRACT Representative glycerol-based solvents were employed as green reaction mediums for various organic reactions. It was found that the solubility of the substrate in the solvent, which depends on solvent polarity, is the main factor that affects reaction performance. In addition, the effect of solvent polarity on product solubility in the reaction solvent determined the effectiveness of product separation by extraction with glycerol immiscible solvent. KEYWORDS: glycerol, glycerol derivatives, green solvent, catalysis, Suzuki cross-coupling 1. INTRODUCTION The search for more environment-friendly routes of chemical synthesis has expanded considerably in recent years [1-3]. As organic reactions proceed mainly in solvents that help bring the reactants and catalysts together and that assist in the transfer of momentum, heat and mass; using green solvents in organic synthesis is among the methods with the most potential to decrease the environmental impact of a chemical process. Moreover, in addition to the nature of each solvent, i.e., its chemical, physical, and biological properties, which define how it can benefit the environment and make it more attractive as a reaction medium, a green solvent is also one that enables easy and simple product separation and catalyst recycling. During the last two decades, a variety of green systems with different alternative solvents have been reported in the literature [1-3]. Among them four main solvent systems are recognized as green reaction mediums: water [4], ionic liquids [5, 6], fluorous solvents [7, 8], and supercritical fluids [9, 10]. Moreover, it is also recognized that no single green solvent can fulfill the requirements for all organic reactions - each of the existing green reaction mediums comes with its particular advantages and disadvantages. Several years ago, we reported for the first time, on the use of glycerol as a sustainable reaction medium in both catalytic and non-catalytic organic syntheses [11]. Since then, glycerol has been successfully employed as a green solvent in a wide variety of organic reactions and synthesis methodologies, and in some examples it was simultaneously used as solvent and reactant [12, 13]. In addition, in different systems, glycerol enhanced reaction activity and selectivity and tolerated easy product isolation and catalyst recycling. Besides its high boiling point, low vapor pressure, thermal stability, and recyclability, the primary advantage of glycerol over most of the above-mentioned green solvents is its renewable origin, which makes it non-toxic, non- irritant, and biodegradable. Moreover, as glycerol is a by-product of simple and relatively non- hazardous oil and fat transesterification in oleochemical and bio-diesel production, the available amounts of glycerol are continuously increasing while its price is decreasing. Yet despite glycerol’s promise as a sustainable solvent for liquid phase organic syntheses, the low solubility of highly hydrophobic compounds and gases in glycerol limits its utilization. However, those limitations can be overcome by using Green Processes Center, Chemical Engineering Department, Sami Shamoon College of Engineering, Bialik/Basel Sts. Beer-Sheva, 84100 Israel Adi Wolfson, Christina Dlugy, and Dorith Tavor Trends in Organic Chemistry Vol. 15, 2011