6958-22-1Relevant articles and documents
Enhancing the kinetics of hydrazone exchange processes: An experimental and computational study
Higgs, Patrick L.,Ruiz-Sanchez, Antonio J.,Dalmina, Milene,Horrocks, Benjamin R.,Leach, Andrew G.,Fulton, David A.
supporting information, p. 3218 - 3224 (2019/03/26)
The capacity of hydrazone bonds to readily undergo component exchange processes sees their extensive utilization in dynamic combinatorial chemistry. The kinetics of hydrazone exchange are optimal at pH ～4.5, which limits the use of hydrazone-based dynamic combinatorial libraries, particularly for biological targets which are only stable at near-neutral pH values. It would thus be advantageous if hydrazone exchange proceeded with faster rates at pH values closer to neutral. We experimentally and computationally evaluated the hypothesis that hydrazones possessing neighbouring acidic or basic functional groups within the carbonyl-derived moitety of the hydrazone would enhance exchange rates. Our work suggests that judiciously placed N- or O-hydrogen bond acceptors within the carbonyl-derived moiety of the hydrazone stabilize transition states via hydrogen bonding interactions, providing a valuable boost to exchange kinetics at near-neutral pH values. We anticipate these findings will be of interest in dynamic combinatorial chemistry, dynamic covalent polymers/materials, functionalized nanoparticles and interlocked molecules, all of which may benefit from hydrazone exchange processes able to operate at near-neutral pH values.
Kinetics and Mechanism of Benzaldehyde Girard T Hydrazone Formation
Stachissini, Antonia Sonia,Amaral, Luciano do
, p. 1419 - 1424 (2007/10/02)
In aqueous solution, Girard T hydrazone formation from para-substituted benzaldehydes does not proceed to completion under the condition used.The corresponding equilibrium constants were determined and employed to calculate the rate of the reaction at completion.For all the reactions studied, the pH-rate profiles, extrapolated to zero buffer concentration, show one break at pH 4-5, characteristic of a change in the rate-determining step from carbinolamine dehydration to carbinolamine formation upon going from pH 7 to pH 1.The formation of the carbinolamine is subject to catalysis by hydronium ion and by carboxylic acids present in the buffers used to maintain pH.Broensted α values for this catalysis varied from 0.19 to 0.37.Rate constants for the cyanoacetic, chloroacetic, and formic acid catalyzed formation of carbinolamine from the para-substituted benzaldehydes correlate with ?+ substituent constants, giving a value of ρ+ equal to 0.70.Rate constants for the hydronium ion catalyzed formation of the carbinolamine from the same benzaldehydes are, however, insensitive to the substituent effect.These observations lead to the conclusion that the reactions occur by different routes as a function of the catalyst.We suggest a stepwise preassociation mechanism for the reaction catalyzed by carboxylic acids and a concerted preassociation mechanism for that catalyzed by hydronium ion.
