Abstract

In this experiment, we monitor changes occurring during the course of a simple reaction, the hydrolysis of acetic anhydride with heavy water (D2O) by a modified in situ reaction monitoring technique. We also take advantage of isotopic substitution to suppress an otherwise large proton signal in the NMR spectrum originating from the reactant/solvent H2O. Isotopic substitution does not alter the potential energy surface along the reaction coordinate, but it will affect the rate of reaction by changing the enthalpy of activation.

Two lesson plans are available

Introduction

In a hydrolysis reaction, a chemical bond is broken by the addition water. Hydrolysis is typically carried out in the presence of a salt of a weak acid or weak base. Water autoionizes into hydroxyl ions (-OH) and hydronium ions (H3O+) and acts as a source of a nucleophile and catalyzing acid, but it is also a weak acid and in most cases hydrolysis in water is too slow for the reaction to proceed without the addition of a strong acid. Hydrolysis of anhydrides are, however, often facile in the presence of water where only mild heating of the reaction mixture is necessary.

The hydrolysis of acetic anhydride (Ac2O) to acetic acid (AcOH) serves as a model example of the hydrolysis reaction. Acetic anhydride rapidly hydrolyzes in the presence of water, alcohol and catalyzing acid, in this case water. We can monitor the evolution of the reaction using NMR by a modified in situ reaction whereby a single aliquot of the reaction mixture is injected into the RF coil of the NMR probe. In situ reaction monitoring by NMR has several requirements:
1) reactants and products must be soluble throughout the course of the reaction
2) signals undergoing change must be resolvable
3) the rate of reaction must be slower than the timescale of the NMR experiment.

In addition to its applications in the determination of static molecular structures, many NMR experiments are performed to monitor the growth and evolution of resonance signals undergoing dynamic change. An example of a time-dependent process is a chemical reaction. During a reaction, resonance signals shift position, coalesce, grow and diminish in intensity. Tracking and extracting chemically relevant information by NMR requires that the timescale of the dynamic process be slower than the so-called NMR timescale. The NMR timescale finds its basis in the uncertainty principle, where the width of resonance, ∆ν, at a given frequency is measurable as a distinct sharp line if the lifetime, 1/τ, of the state is long, ∆ν=h/(2πτ).

As lifetime of the resonance shortens, broadening of the signal occurs. This is referred to as lifetime broadening. Lifetime broadening is evident in the broad resonances observed for rapidly exchanging labile protons, such as in alcohols. The minimum timescale requirement for averaging two closely spaced resonances is the reciprocal of the difference of the peaks. Otherwise, the signals begin to coalesce.

About the author

Dean Antic, Ph.D., is a Senior NMR Applications Scientist, organic chemist and spectroscopist at Thermo Fisher Scientific, San Diego, CA. Formerly, Dean was an adjunct professor of chemistry at Northeastern Illinois University and a certified 9-12 chemistry instructor.

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