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Modules 06710-12-14
H3C
CH3
N
2,7-dimethylquinoline
O
Ph
N
2-phenyl-3,4-dihydroquinoline
N
H
H3C
CH3
N
H
2,7-dimethylquinolin-(1H)4-one
Br
7-bromo-2,3-dihydroindole
OMe
H
N
NH
O
5-methoxyisoquinolin-(2H)1-one
Ph
4-phenyl-1,2-dihydroquinoline
CH3
H
N
N
Br
CH3
3,8-dimethylisoquinoline
2-bromoindole
A2 Name the following heterocycles
O
H3C
Br
N
H
N
H
CH3
6-bromo-2-methyl-1,2-dihydroquinoline
CH3
2,6-dimethylquinolin-(1H)4-one
H
N
MeO
NH
6-methoxy-1,2,3,4-tetrahydroisoquinoline
CH3
CH3
N
H
2,4-dimethylindole
OMe
4-methoxy-2,3-dihydroindole
N
H
1,2,3,4,5,6,7,8-octahydroquinoline
page 1
Modules 06710-12-14
N
Ph
1-phenylisoquinoline
OMe
5-methoxy-7,8-dihydroquinoline
H3C
NH2
Br
2
Br
CH3
Ph
H2N
Ph
O
4
Br
+
Br
H
Ph
NH2
Ph
O
5
NH2
Ph
Et
6
CH3
Et
NH2
O
+
Ph
Ph
Et
Ph
N
F
Et
page 2
CH3
Modules 06710-12-14
CH3
Br
7
H2N
H3C
N
CH2CH3
CH2CH3
Br
B2 Formulate the products from the following reactions, all of which are quinoline,
quinolone or isoquinoline syntheses. Identify key pre-cyclisation intermediates in
each case.
MeO
CH3
H+
NH2
H3C
MeO
CH3
NH
CH3
MeO
MeO
O
H+
+
O2N
O2N
NH
NH2
Cyclisation is to the less hindered para position in the more electron rich ring
Cl
1. Et3N
2. POCl3, heat
Cl
3
Cl
NH2
+
H3C
CH3
O
4
Cl
1. Et3N
2. POCl3, heat
3. Pd-C, heat (no H2)
NH2
H3C
+
1. AcOH, 40 oC,
with azeotropic
removal of H2O
Ph
OEt
NH2
O
H3C
2. Ph2O, 250 oC
N
H
Ph
Ph
o
H3C
+
Ph
1. 150 C,
2. conc. H2SO4
O
OEt
NH2
page 3
H3C
N
H
Modules 06710-12-14
Br
7
H2N
O
Br
NaOH, 0 oC
H3C
Ph
Ph
CH3
CH3
Br
Br
8
NH2
H
H2SO4, heat
B3 Formulate the products from the following reactions, all of which are Fischer
indole syntheses. In each case identify the enamine intermediate prior to the [3,3]sigmatropic rearrangement step.
O
1
NHNH2
H3C
N
H
O
2
NHNH2
H3C
CH3
N
H
CH3
+
NHNH2
N
H
O
Br
4
CH3CH2
H2NHN
Br
CH2CH3
+
NHNH2
H3C
N
H
CH2CH3
Br
CH3
Br
CH3
N
H
CH3
O
NHNH2
MeO
+
6
MeO
N
H
O
7
NHNH2
H3C
Ph
CH3
CH3
page 4
N
H
Ph
Modules 06710-12-14
O
8
+
CH3
NHNH2
CH3
N
H
+
N
H
NHNH2
F
B4 From what starting materials could you make these two indoles? In these
examples, could there be any problems with formation of isomeric indole products? If
so what is (are) their structure(s)?
H3C
CH3
H3C
+
NHNH2
CH3
N
H
only isomer
+
MeO
MeO
NH-NH2
N
H
major isomer
OMe
N
H
minor isomer
MeO
H
+
reaction A
NH2
CH3
CH3
CH3
O
O2N
O2N
H
+
NH2
CH3
reaction B
Reaction A is faster than reaction B. MeO is electron releasing making the ring more
nucleophilic than when the electron withdrawing NO2 is present.
C2
page 5
Modules 06710-12-14
O
MeO
MeO
H
+
reaction A
NH2
CH3
CH3
CH3
O
H
+
MeO
NH2
CH3
MeO
reaction B
Reaction B is faster than reaction A. MeO is o/p director so the position ortho to the
NH2 and para to the OMe is more readily attacked than the one meta to the MeO in A.
C3
MeO
MeO
MeO
CH2O
NH2
NC
NC
NC
NC
NH
NC
NC
reaction B
CH2O
NH2
MeO
MeO
reaction A
NH
MeO
Reaction A is faster than reaction B. As above the MeO is an o/p director but CN is a
deactivating meta director. So the position para to the OMe is more readily attacked
than the one para to the CN.
D:- Electrophilic and nucleophilic reactions of heterocycles
Cl
1
Cl
+
N
heat
HN
Cl
N
(1 mole equivalent)
Cl
heat
Cl
Na O
(1 mole equivalent)
O
Cl
Cl
+
N
Cl
heat
Cl
H2N
(1 mole equivalent)
page 6
N
H
Modules 06710-12-14
CH3
CH3
HNO3 / H2SO4
heat
N
NO2
Br
CH3
N
H
CH3
Br2
N
H
CH3
6
CH3
Br
Br2
N
H
N
H
HO
O
7
N
H
H+ cat
H
N
H
N
O
8
N
H
Br
H+ cat
H
N
H
N
H
Br
CH3I
CO2Et
CO2Et
Br
Cl
9
N
H
I +
N
NaOEt
+
EtO2C
heat
CO2Et
N
H
Br
H
N
N
Cl
N
H
NH2
page 7
N
Cl
N
H