Surfactant-Dependent Partitioning of Organics in Aqueous–Organic Reaction Systems

Abstract

Performing organic reactions in water provides environmental and toxicity advantages compared to in organic solvents, but such strategies are still evolving, limited by current understanding of these multiphasic systems. Here, a fluorescence lifetime imaging microscopy (FLIM) technique characterizes surfactant-dependent partitioning of organics in a system that mimics the early, zinc-related steps of a Negishi-like cross-coupling reaction in water, under synthetically relevant high concentrations of substrate (0.18 M), where large emulsion droplets (5–20 um) form an organic phase. Brij-30 resulted in the highest degree of partitioning of organics in the aqueous phase, which was not predictable from simple hydrophilic–lipophilic balances (HLB). The ionic surfactant CTAC suppressed reactivity of the metallic zinc surface with both neutral (TMEDA) and anionic (carboxylate) reactants, presumably through competitive chloride binding and concurrent cetrimonium coating, a finding that may contribute to the reduced performance of ionic surfactant in the bench-scale coupling reaction.

Buildup and Consumption of Species in Emulsion Droplets during Aqueous Suzuki Coupling Correlate with Yield

“…We recently developed the spatial resolution and microenvironmental sensitivity of fluorescence lifetime imaging microscopy (FLIM) [18][19][20] to provide missing information on the size of emulsion droplets and the partitioning of select reagents under conditions relevant to synthesis, making it an emerging analytical technique in this area. [21][22][23] Specifically, FLIM is the creation of (spatially resolved) images that display the amount of time fluorescent molecules spend in their excited states. To date, evolution of a full catalytic reaction from substrate-to-product in organic-aqueous-surfactant media has not been imaged by FLIM, or by any other type of microscopy, leading to several central questions: 1) Do generated species build up during the reaction, and if so in which location(s)?…”

“…Specifically, the fluorescence lifetimes of organic fluorophores are exquisitely sensitive to their microenvironments. [18][19][20][21][22][23] We envisioned that a hydrophobic spectator fluorophore, 1, doped in at the low loading of 220 nM, would inform on changes in composition of emulsion droplets though changes in its fluorescence lifetime, without chemical involvement in the reaction itself. 21,22,32,33 The anticipated changes in fluorescence lifetime 1 with reaction progress are not known in advance and therefore form part of the research question and technique development process.…”