19F NMR-based lithium sensors using 19F-Labeled aza-crown ethers: Regioisomeric and substituent effects

Abstract

We herein report ¹⁹F NMR-based molecular lithium sensors using ¹⁹F-labeled aza-crown ether derivatives and investigate the regioisomeric and substituent effects on ¹⁹F NMR lithium sensing. Four new fluorinated 1-aza-12-crown-4 derivatives were successfully synthesized via Buchwald-Hartwig amination. Fluorine substitution at the para position relative to the 1-aza-12-crown-4 moiety resulted in a 20-fold increase in chemical shift differences upon exposure to lithium ions, compared to the meta position. We also found that an electron-withdrawing nitro group on the fluorobenzene aza-crown ether prevented any ¹⁹F NMR chemical shifts upon exposure to lithium ions. In contrast, a methyl substituent at the same position as the nitro group induced remarkable (∼20 fold) chemical shifts, similar to the compound without any functional group. In addition, magnesium and calcium, two divalent metal ions prevalent in lithium-containing geothermal brines, were able to bind to ParaF, resulting in ¹⁹F NMR chemical shifts. The slow exchange between ParaF and magnesium enabled the simultaneous detection of lithium (which undergoes rapid exchange) and magnesium when both ions were present. This work provides a rational design principle for developing highly selective molecular lithium sensors.