Phenacyl halides, nucleophilic

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... 

Nucleophilic attack by iV-methylaniline is favoured by electron-withdrawing groups on the amide and acyloxyl side chains. A series of / ara-substituted Af-acetoxy-Af-butoxy-benzamides (138) (Table 6) gave a weak but positive Hammett correlation with a constants (p = 0.13, r = 0.86) °. The analogous reactions of pyridine with para-substituted phenacyl halides in methanol afforded a similar Hammett correlation a, p = 0.25) . The bimolecular rate constants for the limited series of Ai-benzoyloxy-A-benzyloxybenzamides (139) in Table 6 correlated strongly with Hammett a constants (p = 1.7, r = 0.97) °. Stabilization of developing carboxylate character supported the computed charge redistribution in the transition state ... 

The use of diazomethane has been mentioned above. Diazoacetophenone reacts with various salts of pyridine to give phenacylpyridinium salts. In these reactions the diazoketone is probably first converted into a phenacyl halide or ester, which then quaternizes the pyridine. However, the formation of methylpyridinium fluoborate from diazomethane and pyridinium fluoborate probably involves nucleophilic attack by the base upon protonated diazo-methane ii. ... 

A carboxylic acid (not the salt) can be the nucleophile if F is present. Mesylates are readily displaced, for example, by benzoic acid/CsF. Dihalides have been converted to diesters by this method. A COOH group can be conveniently protected by reaction of its ion with a phenacyl bromide (ArCOCH2Br). The resulting ester is easily cleaved when desired with zinc and acetic acid. Dialkyl carbonates can be prepared without phosgene (see 10-21) by phase-transfer catalyzed treatment of primary alkyl halides with dry KHCO3 and K2C03- ... 

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