Development of highly efficient Friedel–Crafts alkylations with alcohols using heterogeneous catalysts under continuous-flow conditions

Abstract

Efficient and highly durable catalysts were developed for Friedel–Crafts alkylation using alcohols under continuous flow conditions.

Recent Advancements in Typical Friedel–Crafts Alkylation Reactions Focused on Targeting Arene Nucleophiles

“…Masuda, Kobayashi, and co-workers reported a highly efficient and sustainable catalyst appropriate for continuous flow synthesis for typical FC alkylations using alcohols and arene nucleophiles (Scheme 17 ). 98 Activated montmorillonite clay was found to be the best catalyst for these reactions after rigorous optimization and investigation of the catalysts under continuous-flow conditions revealed notable variations in activity and reliability. The FC alkylated products were obtained in moderate-to-high yields (up to 99% conversion).…”

Continuous-Flow Synthesis of Δ9-Tetrahydrocannabinol and Δ8-Tetrahydrocannabinol from Cannabidiol

“…Previously, the use of MK10 for the reaction of 1 in flow was reported, but there was no demonstration of long-term stability . Our results are consistent with observations made by others regarding the inconsistent performance of commercial MK10 . This variation could be caused by the availability of acid sites depending on the packing of the clay, and water content within the clay can impact performance.…”

“…29 Our results are consistent with observations made by others regarding the inconsistent performance of commercial MK10. 30 This variation could be caused by the availability of acid sites depending on the packing of the clay, and water content within the clay can impact performance. A consistent reactor performance was not achieved when performing long run experiments using PVP-BF 3 .…”

Selective alkylation of mandelic acid to diarylacetic acids over a commercial zeolite

“…3,6 The use of heterogeneous catalysts for Friedel–Crafts alkylation reactions with alcohols has the potential to overcome the aforementioned limitations, with heteropolyacids and zeolites showing utility in this general transformation. 7–12…”

“…3,6 The use of heterogeneous catalysts for Friedel-Crafts alkylation reactions with alcohols has the potential to overcome the aforementioned limitations, with heteropolyacids and zeolites showing utility in this general transformation. [7][8][9][10][11][12] We herein report that a commercial zeolite, H-Y-30 (CBV760 from Zeolyst), selectively converts mandelic acid to diarylacetic acids through an FC alkylation reaction (hydroxyalkylation) in aromatic solvents. Diarylacetic acid moieties are important scaffolds in active pharmaceutical ingredients [13][14][15][16][17] but simple synthetic routes do not exist at present.…”