412
HETEROCYCLES
N
Cl
NaOMe
N
OMe
N
Cl
NH 3
N
NH 2
N
Cl
RSH
N
SR
N
Cl
R 2 NH
N
NHR
N
Cl
N
Nu
Nu
−
Methylpyridines are called picolines. 2-Picoline
and 4-picoline may be deprotonated by treatment
with a strong base, giving useful anions. The methyl
acidity results because of resonance stabilization
in the conjugate base, providing an enolate anion
analogue. However, pK a values for 2-picoline (32)
and 4-picoline (34) show that they are somewhat less
acidic than ketones.
N
CH 3
2-picoline
(2-methylpyridine)
n-BuLi
N
CH 2
N
CH 2
N
4-picoline
(4-methylpyridine)
n-BuLi
N
N
CH 3
CH 2
CH 2
pK a 34
pK a 32
These anions can now be used as nucleophiles in
a number of familiar reactions, e.g. S N 2 reactions
with alkyl halides, or aldol reactions with carbonyl
compounds.
N
CH 2
RBr
N
R
N
CH 2
RCHO
N
R
OH
N
R
− H 2 O
S N 2 reaction
aldol reaction
It is worthwhile here to relate the behaviour
of 2-chloropyridine and 2-methylpyridine to carbonyl chemistry. If we consider the pyridine ring
as an imine, and therefore a carbonyl analogue (see
Section 7.7.1), then with 2-chloropyridine we are
seeing reactions that parallel nucleophilic substitution
of an acyl halide through an addition–elimination
mechanism. With 2-methylpyridine we are seeing
typical aldol reactions with activated methyl derivatives.
Box 11.1
Nicotine, nicotinic acid, and nicotinamide
Nicotine is an oily, volatile liquid and is the principal alkaloid found in tobacco (Nicotiana tabacum). It can
be seen to be a combination of two types of heterocycle, i.e. the aromatic pyridine and the non-aromatic Nmethylpyrrolidine.