Effect of structure on reactivity in oxime formation of benzaldehydes

Abstract

Second‐order rate constants for substituted benzaldehyde oxime formation increase linearly with the activity of hydrated protons over the pH range ca 2–7. Under these conditions, first‐order rate constants show saturation behavior with increasing hydroxylamine concentration, establishing carbinolamine dehydration as the rate‐determining step. Equilibrium constants for the formation of the neutral carbinolamine are correlated by the σ+ substituent constants; ρ = 1.26. Under more acidic conditions, second‐order rate constants increase less rapidly than the activity of hydrated protons, indicative of a transition to pH‐independent carbinolamine formation, presumably the uncatalyzed addition of amine to aldehyde. The corresponding value of ρ for this process is 1.21. This value, together with that for the equilibrium constants (see above), suggests that C—N bond formation is nearly complete in the transition state. The rate constants for acid‐catalyzed carbinolamine dehydration are correlated by the σ substituent constants; ρ = −0.85. Copyright © 1999 John Wiley & Sons, Ltd.

Investigating Glyoxylate-Mediated Transamination Using Dipeptide Arrays and Proteomic Peptide Mixtures

“…Then samples were loaded on a C18 column with a 1 h wash by buffer A (0.045% TFA) to remove the large excess of glycoxylate, followed by a quick elution using buffer B (90% acetonitrile, 0.05% TFA) to collect the retained peptides. After that, a biotin-hydroxylamine peptide, containing a TEV protease cleavage site, reacted with the N-ter 2-oxoacyl of successfully transaminated peptides through oxime formation. , The peptide mixture was loaded into a C18 column, following a RP-HPLC gradient (0%–80% buffer B in 40 min) to remove the excess of biotin-hydroxylamine peptide. Finally, peptides were enriched by avidin affinity selection, and all successfully modified peptides were eluted by TEV protease cleavage.…”

Kinetics and Mechanism for Oxime Formation from 4-Pyridinecarboxaldehyde N-Oxide

“…A good example of this behaviour is the oxime formation from 4-nitrobenzaldehyde. 16 On the other hand, when the reactivity of the substrate is further increased, no break is observed in the pH-rate profile, e.g. in the pH range from about 1 to 7 when the oxime is formed from very activated 4-formyl-1-methylpyridinium ion.…”

Oximes and Hydrazones in Bioconjugation: Mechanism and Catalysis

“…103 This is supported by the observation that the formation of oximes and hydrazones becomes concentration-independent if the excess of α -nucleophile is sufficiently high. 104 More supporting evidence is provided by density functional theory (DFT) calculations. 105 …”

“…3 to 7, the acid-catalyzed dehydration of the tetrahedral intermediate 67 / 68 is typically the rate-determining step . This is supported by the observation that the formation of oximes and hydrazones becomes concentration-independent if the excess of α-nucleophile is sufficiently high . More supporting evidence is provided by density functional theory (DFT) calculations …”