Pyridines deactivation effects

The influence of other groups in a pyridine or similar ring system is more difficult to assess because no kinetic data are available. The deactivating effect of the bromine atom in the 2-position is greater than that in the 3-position, while 2,6-dibromopyridine is very slow to react with dimethyl sulfate. Esters, amides, and nitriles of nicotinic and isonicotinic acids undergo fairly easy quaternization at about... 

Oxo-, hydroxy and amino groups activate ortho and para positions toward attack by halogens and this far outweighs the deactivating effect of the pyridine nitrogen. Consequently, these compounds are much more reactive than the foregoing examples and this... 

The 1,3-azoles are not very reactive towards electrophilic attack due to the deactivating effect of the pyridine-like nitrogen. However, electron-donating groups can facilitate electrophilic attack, as in the preparation of oxazoles 3.34 and 3.35. Dimethylamino oxazole 3.33 is essentially functioning like an enamine in this reaction. 

An indication of the deactivating effect of replacing a CH=CH by an imine (CH=N-) is that the electrophilic substitution of quinoline and isoquinoline, in which a benzenoid ring is fused to a pyridine ring, takes place in the benzenoid ring at C-5 and to a lesser extent at C-8 (Scheme 4.25). 

AlCls- ( NrAlCb)- + Br+] which can attack the pyridine, the latter being free from the deactivating effect of protonation or coordination [Br+ + CsHsN Br.C5H4N + H+. ( N AICI3)- + H+- NH + AICI3]. 

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