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Fused Ringheterocyclicchemistry3ed 151127020436 Lva1 App6891 PDF
Fused Ringheterocyclicchemistry3ed 151127020436 Lva1 App6891 PDF
Sulphonation
Halogenation
Fischer indole synthesis
The Fischer indole synthesis, which was first discovered in 1883, is still considered as the most popular,
general and efficient approach.
The aryl hydrazones are easily obtained by condensation of a ketone with an aryl hydrazine
The acid-catalyzed cyclization of aryl hydrazones generate indole with loss of ammonia.
The method can be used to generate substituted endols at 2-position (R2 in figure below) which is difficult
to obtain by EAS R1
R1
R1 R2
R2
R2
R1
Basicity of purine
Purine has three basic, pyridine-like
nitrogens with lone-pair electrons in sp2
orbitals in the plane of the ring. The
remaining purine nitrogen is nonbasic and
pyrrole-like, with its lone-pair electrons as
part of the aromatic p electron system.
OH OH OH
N N N
N N N
–OH
N N HO N N HO N
H H N
H
hypoxanthine xanthine
6-hydroxypurine 2,6-dihydroxypurine uric acid (2,6,8-trihydroxypurine)
OH OH Lactam is cyclic amide
N N (NH-C=O) which
N N
O– NH4+ –OH
undergo tautomerism
HO N HO N
N H N
H to lactim (N=C-OH)
ammonium hydrogen urate lactim form lactam form of uric acid
13
DNA base pairing
Methylxanthines are N-methyl derivatives of xanthines, known
alkaloids in coffee, tea, and cocoa.
15
Purine synthesis
Traube synthesis:
Reacting 4,5-diaminopyrimidine
with formic acid to give purine, or
acetic anhydride to give methyl
substituted purine at imidazole ring.
4,5-diaminopyrimidine 8-methyl-9H-purine
Or
Reacting substituted imidazole with
formamide to give substituted
purine at pyrimidine ring
3-methyl-5-aminoimidazole-4-carbonitrile
Quinoline and Isoquinoline
A benzene ring can be fused on to the pyridine ring in two
ways giving the important heterocycles quinoline, with the
nitrogen atom next to the benzene ring, and isoquinoline,
with the nitrogen atom in the other possible position
Quinoline forms part of quinine (anti-
malarial alkaloid) and isoquinoline forms
the central skeleton of the papaverine
(antispasmodic opium alkaloid).
Numbering
The presence of nitrogen in this
structure produces an irregular
distribution of the electron density in
both heterocyclic and carbocyclic
rings, a situation that alters the
physicochemical properties and
reactivity.
Napthalene Quinoline
Basicity of quinolone and isoquinoline
Both N are sp2
This is a hateful
electron greedy wolf
Here we pull e by
protonation, to destroy any
hope for NO2 to come to
pyridine ring
Rxns of quinolone
Electrophilic substitution
Acridine, with two benzene rings, which gives four nitration products, all on the benzene rings.
IF you want electrophils to come to pyridine ring, then give the ring some electrons, e.g. by
formation of N-oxide.
The acridine-N-oxide gives just one product in good yield—nitration takes place at the only
remaining position on the pyridine ring.
Cα
Cβ
This Zigzag bond
Synthesis of quinolines indicate unknown
isomer
o-Acylanilines Plus Carbonyl Compounds
o-Acylanilines condense with enolizable
carbonyl (keto group with adjacent H) to
give quinolines.
The outcome of the condensation was
found to be dependent on the type of
catalyst (acid or base) Here we have
tautomerizatoin also
Synthesis of quinoline
Skraup reaction
conjugate addition of the amine. Under acid catalysis the ketone now cyclizes to give a
dihydroquinoline after dehydration. Oxidation to the aromatic quinoline is an easy step
accomplished by many possible oxidants.
Unsaturated
keton
Aniline
Synthesis of quinoline
Simple example of Skraup reaction
Traditionally, the Skraup reaction was carried out by mixing everything together and letting it rip.
A typical mixture to make a quinoline without substituents on the pyridine ring would be the
aromatic amine, concentrated sulfuric acid, glycerol, and nitrobenzene all heated up in a large
flask at over 100 °C with a wide condenser.
The glycerol was to provide acrolein (CH2=CH·CHO) by dehydration, which provide the necessary 3C to close the ring