Revisiting Hydroxyalkylation of Phenols with Cyclic Carbonates

Abstract

Described is a tetrabutylammonium fluoride-mediated hydroxyalkylation reaction of phenols with cyclic carbonates. This operationally simple method enables the synthesis of a variety of aryl β-hydroxyethyl ethers in good to excellent yields with a very small amount of catalyst loading (0.1-1 mol%). Of particular note is the efficient conversion of aromatic diols and phloroglucinol to the corresponding bis-and tris-hydroxyethylated products. To further showcase the versatility of this protocol, guaifenesin was prepared with a single step by the condensation of guaiacol and glycerol carbonate. We also developed a flow ethoxylation process permitting the continuous synthesis of multiflorol.

Unrevealing the hidden link between sustainable alkylation and hydrogen transfer processes with alcohols

“…[30,31] Innovative applications of cyclic OCs in the field of phenolic hydroxyalkylation have been reported as well. [32,33] Also worthy of note are the reports on the peculiar reactivity of the completely bio-based glycerol carbonate (GlyC) for the O-alkylation of catechol to yield 2hydroxymethylbenzodioxane (HMB). [34] Interestingly, the same approach can also be applied for the synthesis of biobased polyols for the valorisation of lignin.…”

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

“…46 The only other example regarding the reaction between GlyC and a phenolic compound (i.e., guaiacol) to produce the corresponding β-aryloxy alcohol has been performed by exploiting TBAF (tetrabutylammonium fluoride) as a catalyst in toxic DMF as a solvent. 47 For all the reasons mentioned above, the solventless reaction between GlyC and phenol (or its derivatives) is herein reported and extensively investigated for the synthesis of both MPP and DPP, adjusting the reaction protocol and conditions to selectively obtain the former or the latter. In particular, considering MPP production, by working with stoichiometric amounts of reagents, a theoretical atom economy of 79% can Scheme 1.…”

“…Moreover, the coproduction of 2 mol of ethanol per mole of converted DEC decreases the atom economy of the process down to 55%, leading, in addition, to the formation of an even lower boiling point azeotrope (between DEC and ethanol) . The only other example regarding the reaction between GlyC and a phenolic compound (i.e., guaiacol) to produce the corresponding β-aryloxy alcohol has been performed by exploiting TBAF (tetrabutylammonium fluoride) as a catalyst in toxic DMF as a solvent …”

Synthesis of Cyclic Carbonates Catalyzed by CaI2–Et3N and Studies on Their Biocatalytic Kinetic Resolution

“…Furthermore, we became interested in obtaining pure chiral cyclic carbonates since they are potential chiral building blocks − and only few studies focus on their enantioselective synthesis. One possible approach is the kinetic resolution of epoxides using chiral metal complexes which selectively convert the epoxide to the corresponding carbonate .…”