Page 182 - Academic Press Encyclopedia of Physical Science and Technology 3rd Organic Chemistry

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Encyclopedia of Physical Science and Technology EN007F-314 July 6, 2001 16:59

338 Heterocyclic Chemistry

1. Pyridines and Pyridinium Salts Hydrogenated derivatives of pyridine are often used in
alkaloid synthesis; heterocyclic enamines undergo vari-
A simple route to pyridinium salts is by direct alkylation
ous cyclization and annelation reactions. Complete hy-
of pyridines, the Menschutkin reaction.
drogenation of pyridine leads to piperidine. Coniine, or
alpha-propylpiperidine, is a poisonous principle in hem-
+ MeI
+ _ lock, from which Socrates died. The synthesis of coniine
N N I
by Ladenburg in 1886 is the earliest recorded synthesis of
Me
an alkaloid.
The pellagra-preventive nicotinic acid and the powerful
weedkiller paraquat are examples of important pyridine N acid N
derivatives.
N N
H H
COOH
+ +
Me N N Me O O
an enaminoketone
N
nicotinic acid paraquat
The antagonist nicotinamide adenine dinucleotide α
(NAD ) also contains a pyridinium ring. N H N
+
H
piperidine coniine
CONH 2
+
O O N
_ P O
O 2. Quinolines, Isoquinolines,
O NH 2
N and Their Derivatives
O HO OH
P
HO O N N Formal benzannelation of pyridine gives quinoline and
O N
isoquinoline; bisbenzannelation gives phenanthridine and
acridine. Whereas the former is numbered systematically,
HO OH
it should be noted that acridine is not, the central ring being
+
nicotinamide adenine dinucleotide (NAD ) numbered finally.
Pyridine is present in bone pyrolyzates and coal tar, 2
from which it was isolated in 1846 by Anderson. It is now 1 3
10 8 9 1
prepared industrially from tetrahydrofurfuryl alcohol and 9 4 7 2
ammonia. Nicotine (in tobacco), the antibacterial agent 8 N 5 6 N 3
sulfapyridine, and the benzene cofactor pyridoxine (vita- 7 6 5 10 4
min B 6 ) are three important pyridines. phenanthridine acridine
Acridine dyestuffs, such as acridine orange L, owe their
NH 2
OH
color to the extensive delocalization of cationic charge.
HO
N OH
Me
SO 2
N N N N + +
H Me 2 N N NMe 2 Me 2 N N NMe 2
_ _
nicotine sulfapyridine pyridoxine H Cl H Cl
acridine orange L
As for five-membered rings, common routes to six-
membered rings involve condensation, ring closure, and There are several important routes to quinolines. In the
cycloaddition reactions. In the Hantzsch pyridine synthe- Skraup reaction, an aniline is heated with a mixture of
sis, 2 moles of a beta-dicarbonyl compound are condensed glycerol, nitrobenzene, and sulfuric acid to give a quino-
with 1 mole of an aldehyde in the presence of ammonia line.
to give, after oxidation, a pyridine.
OH
Ph Ph OH
PhNO 2
+
MeOOC CHO COOMe 1. NH 3 , AcOH, ∆ MeOOC COOMe H 2 SO 4
NH 2 OH N
2. HNO 3
O O N Skraup synthesis of quinoline