The structures and stabilities of biologically active 1-phenacyl- and 1-benzoylethyl-derivatives of the pyridinium cation

Tandem β-Elimination/Hetero-Michael Addition Rearrangement of an N-Alkylated Pyridinium Oxime to an O-Alkylated Pyridine Oxime Ether: An Experimental and Computational Study

“…This result indicated that the most acidic position in H 2 -BEPA4 + is the hydroxyl group of the oxime moiety. The calculated p K a1 ( H 2 -BEPA4 + ) oxime value of 8.2 is in good agreement with the measured value of 8.51 ± 0.04 previously presented . The first deprotonation of H 2 -BEPA4 + produces H-BEPA4 , in which the keto form is even more favored over the enol by 9.7 kcal mol –1 .…”

“…On the basis of the fact that β-elimination was the exclusive reaction in the pH range 7–10 and tandem β-elimination/hetero-Michael addition occurred at pH >10, two kinetic experiments were conducted to elucidate the rate-limiting step: determination of the reaction activation parameters in the OH – /H 2 O and the BRB systems (Table and Table S2 (Supporting Information)) and examination of the solvent polarity on the rearrangement reaction rate in the OH – /H 2 O/EtOH systems at pH 11.0 (Table S3 (Supporting Information)). The inspection of the Δ H ⧧ and Δ G ⧧ values determined in the BRB system provided strong evidence that the same type of transition state was formed in the pH range 8.3–11.2 and revealed base-induced β-elimination as the rate-limiting step.…”

“… a The drift in the temperature measurements was ±0.1 °C. b The Δ G ⧧ values were calculated at 298 K using the relationship Δ G ⧧ = Δ H ⧧ – T Δ S ⧧ . c The exclusive β-elimination of H-BEPA4 occurred …”

“…As part of our ongoing research program aimed at investigating the pentacyanoferrate(II) complexes of pharmacologically active pyridinium-4-oxime derivatives, our recent research has been focused on the comparative structural studies of the N -phenacyl and N -benzoylethyl derivatives of pyridinium and pyridinium-4-oxime in aqueous solutions . The investigation of the stability of these compounds in mild and highly alkaline media revealed substantial differences in their reactivity.…”

“…As part of our ongoing research program aimed at investigating the pentacyanoferrate(II) complexes of pharmacologically active pyridinium-4-oxime derivatives, 13 our recent research has been focused on the comparative structural studies of the N-phenacyl and N-benzoylethyl derivatives of pyridinium and pyridinium-4oxime in aqueous solutions. 14 The investigation of the stability of these compounds in mild and highly alkaline media revealed substantial differences in their reactivity. One can reasonably assume that, under these conditions, the focus would be on the reactivity of the carbonyl group, and this was true in the case of the N-phenacyl derivatives and the N-benzoylethylpyridinium cation, where the structural perturbations were initialized by the addition of the hydroxide ion to the carbonyl group.…”