Separation of polar and resonance substituent effects in the reactions of acetophenones with bisulfite and of benzyl halides with nucleophiles

Abstract

Application of the modified Yukawa-Tsuno equation log ( k / k o ) = p a n + p r ( u +a n ) to the reversible reaction of bisulfite with substituted acetophenones gives p = 0.6 and p r = -0.45 for the hydroxide ion catalyzed cleavage reaction, p = 1.8 and p r = 0.45 for attack of sulfite dianion, and p = 1.2 and p r = 0.95 for K,, for bisulfite addition. Rate constants for the cleavage reaction exhibit a U-shaped Hammett plot and require a negative value of the r+ parameter, although the reaction is facilitated by electron donation by resonance. Furthermore, the values of p and p r for the equilibrium and rate constants in the two directions are additive, but the r+ values are not. The same treatment accounts for most of the curvature in Hammett plots for the S N~ reactions of nucleophiles with benzyl halides without invoking changes in mechanism or transition-state structure. The changes in transition-state structure that do occur in some of these reactions are discussed and it is suggested that the "reactivity-selectivity principle" represents an oversimplification that should be abandoned for all but the simplest reactions.

Computational Study of Reactivity and Transition Structures in Nucleophilic Substitutions on Benzyl Bromides

“…The observed changes in reactivity have been interpreted [9] in terms of opposing e-d resonance and e-w polar effects, without any change in the mechanism or 5570 strates bearing e-w groups were higher than expected. No breaks in the ∆G ‡ /∆H ‡ /∆S ‡ vs. σ plots were observed when the substituents on the pyridine nucleophile were changed.…”

“…Bond orders (n) [a] for the TS 11a generated in the reaction between benzyl bromide and pyridine (Scheme 2). By using the Br-C 7 and N-C 7 bond lengths (R o ) in benzyl bromide (1a) and N-benzylpyridinium ion (14a), and the Br···C 7 and N···C 7 bond lengths (R S ) in the symmetric (n = 0.5) TSs 6a and 15, respectively, we first calculated the constants a for Equation (9) and then the bond orders n for TS 11a with the Br···C 7 and N···C 7 bond lengths (R R ). The data in Table 2 indicate that late TSs are formed in vacuo (i.e., the unfavorable formation of ions requires a strong nucleophilic attack).…”

Aliphatic Nucleophilic Substitutions: Problematic Electrophiles

“…Accordingly, constrained benzylic substrates in which such conjugation is not possible are not as reactive as similar, unconstrained systems. Because donor-substituted benzylic systems tend to undergo rapid Sn1 reactions, the reactivity of benzylic electrophiles toward negatively charged nucleophiles usually reaches a minimum for unsubstituted benzylic electrophiles and increases on substitution with either electron-withdrawing or electron-donating substituents [114][115][116][117] (Scheme 4.25). In compound A cleavage of the benzylic C-S bond by a nucleophile has to proceed via a transition state in which the Nuc-C-SR 2 + trajectory is almost parallel to the arene and no conjugation with the aromatic p-system is possible.…”

Photoelectron spectra of substituted acetophenones. Correlations with reactivity

“…Young and Jencks have studied the reversible reaction of bisulfite with substituted acetophenones (19). In that investigation a modified Yukawa-Tsuno equation (20) was used to separate substituent effects into polar and resonance components.…”