Real‐time mechanistic monitoring of an acetal hydrolysis using ultrafast 2D NMR

Abstract

Ultrafast (UF) 2D NMR makes it possible to obtain a 2D NMR spectrum in less than a second. Here, UF-HSQC experiments are used for the real-time mechanistic study of an acetal hydrolysis at ¹³C natural abundance, and it is possible to characterize the presence of the hemiacetal, an intermediate with a well-known short lifetime. The assignments are confirmed and rationalized by quantum calculations of ¹H and ¹³C NMR chemical shifts and natural bonding orbital analysis.

Monitoring organic reactions by UF‐NMR spectroscopy

“…Giraudeau et al solved this problem by monitoring an acid‐catalyzed acetal hydrolysis reaction by UF‐HSQC experiments at natural abundance . Figure shows the organic reaction chosen, the hydrolysis of the 2‐(4‐nitrophenyl)‐1,3‐dioxolane acetal ( 29 ) with trifluoroacetic acid (TFA).…”

“…Gradient‐based coherence selection and phase cycling efficiently removed the signal from 1 H bound to 12 C, making it possible to work at natural 13 C abundance. Finally, a two‐pulse spatial encoding was chosen . The study first acquired a spectrum of the acetal alone.…”

“…The cross‐peaks from the reactant 29 , hemiacetal intermediate 30 , and product 31 are highlighted. Figures are taken from Queiroz et al …”

Optimization and practical implementation of ultrafast 2D NMR experiments

“…36 These values seem quite high, but lower concentrations are easily reached by signal averaging, a "multi-scan single shot" approach whose potentialities have been recently demonstrated. 37 Following these developments, ultrafast NMR has been recently applied to a variety of situations, such as monitoring of fast organic reactions, 28,38 the study of biologically relevant samples, 30,38 coupling with hyphenated techniques 39 and measurement of residual dipolar couplings in oriented media. 40 We are currently applying these experiments to the study of dynamic processes occurring on a very short timescale that could not hitherto be followed by any other kind of 2D NMR experiment.…”

“…26,27 Following these improvements, UF-NMR has been applied successfully in a broad range of domains, including the study of mechanistic, 28 kinetic 29 or dynamic 30 processes, the coupling with ex-situ Dynamic Nuclear Polarisation 31 or the application to quantitative analysis.…”