2-Halogenopyridinium salts

Many examples of the usual route to /S-lactams via imines and acid chlorides, ketens, or keten equivalents have appeared.These include syntheses of 3-[bis(alkylthio)methylenamino]-2-azetidinones, ° of spiro-azetidinones and bis-azetidinones, and the use of l-methyl-2-halogenopyridinium salts to activate carboxylic acids towards coupling with imines. A non-hazardous alternative route to 3-amido-2-azetidinones, avoiding the use of azidoacetyl chloride, involves the reaction of Schiff bases with salts of [(a-methyl-/3-methoxycar-bonyl)vinylamino]acetic acid, e.g. (20), in the presence of ethyl chloroformate, as shown in Scheme 5. Formaldimines can be generated from their trimers by treatment with Lewis acids immediately prior to reaction with acid chlorides, so allowing the formation of the nocardicin nucleus which is unsubstituted at C-4. ... 

The behaviour of acylpyridinium, acyloxypyridinium and oxide quaternary salts, and the occurrence of acid catalysis in nucleophilic replacements (pp. 215, 233, 242) lead to the expectation of high reactivity towards nucleophiles in quaternary pyridinium salts. Quantitatively, the reactivity sequence in the reaction of halogen compounds with alkoxides is quaternary salt > oxide > pyridine. The positional sequence is 4 > 2 > 3 in halogenopyridines and their 1-oxides, and 2 > 4 > 3 in the 1-methyl-halogenopyridinium salts. However, in all three series activation energies would give the order 4 > 2 > 3 for the quaternary salts this order is modified by the entropy factor. 

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