Uncatalyzed Strecker‐Type Reaction of N,N‐Dialkylhydrazones in Pure Water

Abstract

Aldehyde and ketone N,N-dialkylhydrazones behave as a stable class of imine surrogates exhibiting a unique reactivity in the Strecker reaction with in situ generated HCN, that proceeds in pure water in the absence of co-solvents, catalysts or promoters. Experimental evidence suggests that the reac-

“On Water” Nucleophilic Addition of Formaldehyde N,N‐Dialkylhydrazones to α‐Keto Esters

“…This zwitterionic intermediate, stabilized by a N⇔︁O electrostatic interaction, would then easily afford product 5 after deprotonation of the methylene group with the regeneration of a molecule of water. The proposed association of water with the hydrazone sp 2 N atom has been previously proposed to explain the reactivity of related hydrazones in hydrocyanation reactions performed in pure water 16. Moreover, a similar hydrogen‐bonding interaction between 2 and a hydroxyl group of a catalyst has been demonstrated to be essential in the asymmetric addition to γ,δ‐unsaturated β‐keto esters 8.…”

“…[16] Moreover, a similar hydrogen-bonding interaction between 2 and a hydroxyl group of a catalyst has been demonstrated to be essential in the asymmetric addition to g,d-unsaturated b-keto esters. On the other hand, the poor reactivity observed in methanol could be tentatively explained by an activation mechanism in which the two protons of water are involved.…”

Ultrasound-assisted multicomponent synthesis of 4H-pyrans in water and DNA binding studies

“…Furthermore, the advantages of using water would be in agreement with some of the twelve principles of Green Chemistry [40][41][42][43][44] . However, despite the number of processes that have been investigated and developed in water, maybe because of the good solubility of reactants is generally considered a prerequisite for an appropriate reactivity, water is still not commonly used as a sole solvent for organic reactions [45][46][47][48][49] . For all these reasons, the development of reactions in pure water is still a challenging task.…”

Uncatalyzed Three‐Component Synthesis of α‐Hydrazido Phosphonates

“…[20] Unfortunately, the reaction does not work, perhaps because of the high tendency of these hydrazones to act as nucleophiles instead of as electrophiles (Scheme 1). [21] Scheme 1.…”