Glycerol Carbonate as a Versatile Alkylating Agent for the Synthesis of β-Aryloxy Alcohols

The possibility to use glycerol carbonate (GlyC) as an innovative alkylating agent for phenolic compounds in solventless conditions and the presence of a catalytic amount both homogeneous heterogeneous bases is herein described. In particular, peculiar, polyfunctional structure GlyC allows one obtain formation not only mono-phenoxy-1,2-propanediol (MPP) analogue but also 1,3-diphenoxy-2-propanol (DPP), latter being elusive using more traditional, toxic, carcinogenic reagents such glycidol and/or 3-chloro-1,2-propandiol. production DPP indeed possible due situ reactive intermediate, 4-(phenoxy)methyl-1,3-dioxolane-2-one (PhOGlyC), which may undergo consecutive nucleophilic attack phenolate, leading selective disubstituted product. This reaction nonetheless competition with PhOGlyC decarboxylation that finally limits yield up 20%, MPP roughly 60% optimized (atmospheric pressure, 140 °C, 5 h Cs2CO3 basic catalyst) starting directly from GlyC/phenolic mixture. For this reason, multistep synthetic strategy has been developed, first by obtaining quantitative isolation intermediate then promoting phenol, way 66% after 1 at 170 °C. obtained phenyl glyceryl ethers are interesting drugs scaffolds (i.e., guaifenesin, mephenesin), intermediates preparation active pharmaceutical ingredients (e.g., chlorphenesin carbamate, methocarbamol), hydrotropic solvents; preliminary evaluations biodegradability alternative surfactants have described paper.