Use of Diethanolamine as a Viscous Solvent for Mixture Analysis by Multidimensional Heteronuclear ViscY NMR Experiments

Abstract

The use of diethanolamine/DMSO-d 6 as viscous binary solvent is reported for the individualization of low-polarity mixture components by heteronuclear ViscY NMR experiments under spin diffusion conditions. Solvent viscosity induces the slowing down of molecular tumbling, hence promoting magnetization transfer by dipolar longitudinal cross-relaxation. As a result, all 1 H nuclei resonances within the same molecule may correlate in a 2D NOESY spectrum, giving access to mixture analysis. We state the individualization of four low-polarity chemical compounds dissolved in diethanolamine/DMSO-d 6 solvent blend using homonuclear selective 1D and 2D 1 H and 19 F NOESY and HOESY experiments and heteronuclear

ViscY nuclear magnetic resonance experiments for in situ chemical reaction monitoring under spin diffusion conditions

“…ViscY is a collective name for NMR experiments that take benefit from spin diffusion in viscous solvents for the individualization of NMR spectra of the components of small molecule mixtures. 6–8 According to the microviscosity theory of Gierer and Wirtz, the value of the overall rotational correlation time τ c of a compound in solution depends on the medium's viscosity (see equation in ESI†). 9 Therefore, when the medium viscosity is high, the tumbling rate of small and mid-sized molecules is slow so that the longitudinal cross-relaxation becomes very efficient and thus promotes spin diffusion over entire molecular spin networks (quantitative aspects described in ESI† 10 ).…”

“…Our research team reported original results in mixture analysis by ViscY NMR using glycerol and glycerol carbonate (in 2011), 12 DMSO/glycerol (in 2016), 13 DMSO/water (in 2017), 14 sucrose solution, agarose gel (in 2019), 15 sulfolane-based solvents (in 2020), 6 phosphoric acid solutions (in 2021), 7 and diethanolamine (in 2022). 8…”

“…Our research team reported original results in mixture analysis by ViscY NMR using glycerol and glycerol carbonate (in 2011), 12 DMSO/glycerol (in 2016), 13 DMSO/water (in 2017), 14 sucrose solution, agarose gel (in 2019), 15 sulfolane-based solvents (in 2020), 6 phosphoric acid solutions (in 2021), 7 and diethanolamine (in 2022). 8 The present work focuses on the monitoring of a model reaction, the synthesis of a 3-substituted 4-hydroxycoumarin derivative (4a) through C-alkylation of 4-hydroxycoumarin (1a, 20 mM) with benzaldehyde (2a, 20 mM) and N,N-m-dimethyltoluidine (3a, 20 mM) (see Scheme 1) in the viscous binary solvent DMSO-d 6 /H 2 O (7 : 3, v/v) by 1D and 2D NMR ViscY experiments such as selective 1D NOESY and conventional 2D NOESY experiments. This chemical reaction was chosen due to its compatibility with DMSO and water as solvents, as reported by Kumar et al in 2012.…”