Chemistry Reference
In-Depth Information
Box 11.1 (continued)
NH
2
CONH
2
N
O
O
N
P
P
N
CH
2
O
O
O
CH
2
N
N
O
OH
OH
O
RO
OH
HO
OH
R = H, NAD
+
R =
P
, NADP
+
An intriguing feature of nicotinic acid formation in animals is that it is a metabolite produced from the
amino acid tryptophan. This means the pyridine ring is actually formed by biochemical modification of the
indole fused-ring system (see Section 11.8.2), and, as you might imagine, it involves a substantial sequence of
transformations.
CO
2
H
CO
2
H
NH
2
H
N
L
-tryptophan
(indole ring)
nicotinic acid
(pyridine ring)
11.4.2 Nucleophilic addition to pyridinium
salts
is normally easier at positions 2 or 6, where the
inductive effect from the positively charged nitrogen
is greatest; but, if these sites are blocked, then attack
occurs at position 4. This is easily predicted from a
consideration of resonance structures.
The reaction of nucleophiles with pyridinium salts
leads to addition, giving dihydropyridines. Attack
N
R
N
R
N
R
N
R
Thus, treatment of
N
-methylpyridinium salts with
cyanide produces a mixture of 2- and 4-cyanodi-
hydropyridines, with the 2-isomer predominating.
It is quite difficult to reduce benzene or pyridine,
because these are aromatic structures. However, par-
tial reduction of the pyridine ring is possible by using
complex metal hydrides on pyridinium salts. Hydride
transfer from lithium aluminium hydride gives the
1,2-dihydro derivative, as predictable from the above
comments. Sodium borohydride under aqueous con-
ditions achieves a double reduction, giving the
1,2,5,6-tetrahydro derivative, because protonation
through the unsaturated system is possible. The final
reduction step requires catalytic hydrogenation (see
Section 9.4.3). The reduction of pyridinium salts is
of considerable biological importance (see Box 11.2).
CN
KCN
N
Me
N
Me
CN
N
Me
major
product
minor
product
