heterocyclic rings pyridne, quinoline and isoquinoline
DESCRIPTION
Pyridne Pyridine is a water -miscible liquid, b. p. 115 oC with an unpleasant odour An Excelent polar solvent, A base (pka = 5.23) Pyrrole is less basic than pyridine becuase the lone pair of electrons in pyrrole is part of the aromatic ring, while that in pyridine is free.TRANSCRIPT
Heterocyclic Rings
Pyridne, quinoline and isoquinoline
PyridnePyridine is a water -miscible liquid, b. p. 115 oC with an
unpleasant odourAn Excelent polar solvent, A base (pka = 5.23)Pyrrole is less basic than pyridine becuase the lone pair
of electrons in pyrrole is part of the aromatic ring, while that in pyridine is free.
NNH
:
Pyridine Pyrrole
N CH3 N
CH3
N
CH3
N
COOH
N
COOH
Picolines
N
N
H
CH3
nicotinic acid isonicotinic acid
Tobacco alkaloid (nicotine)Alkaloide (alkali like)
1) The Hantzsch Synthesis1,3-dicarbonyl compound + ammonia + aldehyde
CH3 O
MeO2C
CH3O
CO2Me
NH3
HAr
O
CH3 NH2
MeO2C
CH3O
CO2Me
Ar
H
NH2CH3
CH3
Ar
CO2MeMeO2C
ONH
Ar
CH3 CH3
CO2MeMeO2C
+
Conjugate addition (1,4-addition)
enamine enone
+
CH3 NH2
MeO2C
ArO
Cl
H
NH2CH3
Ar
Cl
CO2MeMeO2C
O
NCH3 Ar
MeO2C
+
Conjugate addition (1,4-addition)
enamine enone
Unsymetrical pyridine can be prepared from different enamines and enones
2) Reaction of Ammonia + 1,5-diketone
O O
NH3
NH
N
Oxidation
3) Diels-Alder Reaction
NO
X
N
X
N
R
Ph
CO2H
CO2H N
R
Ph
CO2H
CO2H
N
CF3
N
CF3
N
CF3
+-H2O
+
+400 oC heat
-H2
N
COOR
Tos N
COOR
Tos N
N
Ph
N
Ph
Ph
Ph
Ph
PhO
PhPh
PhPh
+ [O]
+heat
- CO
4) Kroehnke Synthesis
Chemistry of Pyridine
N N
CH3
N
N
N
R O
N
R Cl
O
CH3I+
I-
+Cl-
A good acylating agent
N N
O
R OOH
O
PX3
N
NHO3, H2SO4
N
O
NO2
PX3
N
NO2
N
O
NH2
PX3
N
NH2
+
-
Use of N-Oxides
+
-
+
-
H2 / Pd
Electrophilic SubstitutionPyridine is million times less reactive than benzene
Nitration (less than 5%, Chlorination in moderate yield, Bromination in a good yield)3-position is usually attacked preferably
ChiChibabin Reaction (Nucleophilic Substitution)
N N NH2
H
Na+
N NH2
NaNH2
-
-NaH
Quinoline and Isoquinoline
NN
12
3
44'56
78 8' 1
2
3
44'56
78 8'
Quinoline Isoquinoline
Quinoline Skraup Synthesis
O
NH2 NH
O
N
Aniline + Glecerol + H2SO4 quinoline
O
NH2 NH
O
N
Doebner-von Millar
+
Combes Synthesis
RO
O
RNH2 N R
R
H
O
NO2
R
O R2 N
R
R2+
Base1)
2) Reduction
Friedlaender Synthesis
Isoquinoline Synthesis, Bischler-Napierlaski
NH2
MeO
MeO
R Cl
O
NH
MeO
MeO
R
O
MeO
MeON
R
MeO
MeON
R
POCl3
Pd
Pictet-Spengler Synthesis
NH2
R H
O
N
R
MeO
MeONH
R
H+
Pomeranz-Fritsch Synthysis
OR
H
O
H2NCH2CH(OEt)2
ORN
OEtEtO
H
ORN
H2SO4
Chemistry of Quinoline and Isoquinoline Nucleophilic Substitution (ChiChibabin Reaction)
N
N
NaNH2
NaNH2
N NH2
N
NH2
N
N
KOH
KOH
N OH
N
OH
NH
O
NH
O
225 o
C
225 o
C
Electrophilic SubstitutionOccurs at the 5- or 8-positions, or both
Quinoline N-Oxides can be nitrated at the 4-position or photoisomerize as follows