Electron-withdrawing groups, effect nucleophilic substitutions

Electronic effects. Nucleophilic attack is favoured by electron-withdrawing groups on the amide and the acyloxyl side chains. Interpolated bimolecular rate constants at 308 K for the series of para-substituted /V-acetoxy-/V-butoxybenzamides 25c, 26b-g and 26i (Table 5) gave a weak but positive Hammett correlation with a constants ip = 0.13, r = 0.86).42,43 These Sn2 reactions are analogous to those of aniline and substituted pyridines with phenacyl bromides, which have similar Arrhenius activation energies and entropies of activation in methanol (EA= 14-16 kcal mol-1, AS = — 27 to —31 calK-1 mol-1) and 4-substituted phenacyl halides afforded a similar Hammett correlation with pyridine in methanol (cr, p — 0.25).175... 

The effects of other substituent groups on the reactivity of ring halogen atoms are predictable. Electron-donating substituents make nucleophilic substitution more difficult while electron-withdrawing substituents facilitate the process. The effect of an electron-withdrawing substituent which is so positioned that it can participate in resonance stabilization of the intermediate adduct can be considerable. 

Nitrogen protonation or incorporation of high oxidation state metal ions facilitates nucleophilic substitution (especially at Craeso) whereas N-deprotonation or coordination to low valent metal ions enhances the electrophilic reaction (especially at Cme50). The effects of electron-donating substituents (alkyl) are less than those of electron-withdrawing groups (especially n acceptors, N02, COR). 

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