Comparison of the kinetics of aldehyde sensing by covalent bond formation with hydrazines and hydroxylamines

Analytical techniques for the detection of aldehydes often involve reaction with either a hydrazine or hydroxylamine derivative, resulting in the formation of a hydrazone or oxime, respectively. While there are various examples for the use of either type of derivatization reagent, there have been only few reports with data suitable to answer which of the two types of probes allows faster and more selective detection of aldehydes. Addressing this question, this work used ¹H NMR spectroscopy to study the kinetics of the reactions of aromatic and aliphatic aldehydes with two derivatization probes, phenylhydrazine or O-phenylhydroxylamine, in tetrahydrofuran and in presence of an excess of acid catalyst. A fitting procedure was developed to determine the rate constants of these second order reactions while avoiding use of either aldehyde or probe in a large excess. Hydrazone formation was found to be on average 71 times faster than oxime formation. The rate constants for the reaction of aromatic aldehydes with the phenylhydrazine follow largely the trend predicted by Hammett substituent constants, with the notable exception of the hydrogen bond forming 2-hydroxybenzaldehyde. Unlike in studies with water as solvent, aliphatic aldehydes were not found to react faster than aromatic ones.