Pyridines 37We give two more illustrations of the utility of dihydropyridines formed by nucleophilic addition to pyridinium salts.
A non-isolated intermediate is involved in the only practical method for the synthesis of 3-nitropyridines from pyrid-
ines: reaction with dinitrogen pentoxide, N 2 O 5 (or NO 2 OCOCF 3 formed from HNO 3 and (CF 3 CO) 2 O) then hydrogen
sulfi te proceeds by initial formation of a 1-nitropyridinium salt followed by -addition of hydrogen sulfi te to give a
dihydropyridine, in which the nitro group then migrates from nitrogen to carbon, loss of sulfurous acid completing
the overall C-substitution.
Other nucleophiles will also react at C-2 of a 1-nitropyridinium salt leading, following loss of the nitro as nitrite, to
2-substituted pyridines, for example 2-cyanopyridines.
It is possible to replace an -chlorine with bromine or iodine by reaction with the halotrimethylsilane: this involves an
intermediate 1-trimethylsilylpyridinium salt.
C-metallated pyridines
Direct deprotonation of pyridine can be carried out regioselectively at an -position, using the mixed base produced
from two mole equivalents of n-butyllithium with one of dimethylaminoethanol, that is a 1:1 mixture of n-BuLi and
Me 2 N(CH 2 ) 2 OLi (BuLi-LiDMAE).