HETEROCYCLIC CHEMISTRY Part 2

Modules 06710-12-14

HOMEWORK / REVISION / TEST YOURSELF QUESTIONS

A1:- Naming heterocycles Match the following heterocycles with the names given

Ph

N
H

Br

H3C

N
O

CH3

H3C

N
H
H
N

CH3

OMe

NH

Ph
CH3

H
N

Br

CH3
2-bromoindole
5-methoxyisoquinolin-1-one
2-phenyl-3,4-dihydroquinoline
2,7-dimethylquinolin-4-one

3,8-dimethylisoquinoline
4-phenyl-1,2-dihydroquinoline
7-bromo-2,3-dihydroindole
2,7-dimethylquinoline
A2 Name the following heterocycles

Br

H3C
CH3

N
H

CH3

N
H
H
N

MeO
NH

OMe

CH3
CH3

N
H

N
H

N
Ph

OMe

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HETEROCYCLIC CHEMISTRY Part 2

Modules 06710-12-14

B:- Formulation of heterocyclic products

B1 Formulate the products from the following reactions, all of which are the Doebnervon Miller variation of the Skraup quinoline synthesis. Identify key pre-cyclisation
intermediates in each case.
H
+

H3C

NH2

Br
2

H2N

Ph

CH3
3
CH3

H3C

NH2

O
4

Br

?
Ph

NH2

O
5
NH2

Ph

?
CH3

Et

Et
NH2

O
+

Ph

Br
7
H2N

H3C

?
CH2CH3

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HETEROCYCLIC CHEMISTRY Part 2

Modules 06710-12-14

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

NH2

H+

+
H3C

MeO
O
2

H+

+
O2N

H
NH2

1. Et3N
2. POCl3, heat

Cl
3
Cl

NH2

+
H3C

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

H3C
+

?
2. Ph2O, 250 oC

1. 150 oC,
2. conc. H2SO4

Ph

OEt

NH2

Br
7

H2N
O

NaOH, 0 oC

H3C

?
Ph

CH3

Br
8

NH2
H

H2SO4, heat

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HETEROCYCLIC CHEMISTRY Part 2

Modules 06710-12-14

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

O
2
NHNH2

H3C

CH3

NHNH2

Br
4

CH3CH2

H2NHN

Br

CH2CH3

+
NHNH2

H3C

CH3

O
NHNH2
+

MeO

O
7
NHNH2

H3C

Ph

CH3

O
8

CH3
NHNH2

O
+

NHNH2

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HETEROCYCLIC CHEMISTRY Part 2

Modules 06710-12-14

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)?
1

H3C

?
CH3

N
H

?
MeO

N
H

.
C:- Effect of substituents on reaction rate
For each of the following pairs of reactions, which will have the faster rate of reaction
and why?
C1
O
MeO

MeO

H
+

reaction A

NH2

CH3

CH3

CH3

CH3

CH3

O
O2N

O2N

H
+
NH2

CH3

reaction B

C2
O
MeO

MeO

H
+

reaction A

NH2

CH3
O
H
+

MeO

NH2

CH3

MeO

reaction B

C3
MeO

MeO
NC

NH2

NC

NC

NC
MeO

MeO

CH2O
NC

NH

NC
reaction B

CH2O
NH2

reaction A

MeO

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MeO

NH

HETEROCYCLIC CHEMISTRY Part 2

Modules 06710-12-14

D:- Electrophilic and nucleophilic reactions of heterocycles

Cl
1

Cl

heat

HN

+
N

(1 mole equivalent)

Cl

heat

Na O

(1 mole equivalent)
Cl

Cl

heat

+
N

H2N

Cl

(1 mole equivalent)

CH3
4

heat

HNO3 / H2SO4

Br2

Br2

CH3

N
H

CH3
6

N
H

O
7

N
H

H+ cat
H

O
8

N
H

Br

?
C13H17NO

H+ cat
H

N
H
NaOEt
+
EtO2C
?
heat

Cl
9

CH3I

CO2Et
?

N
Cl
N
H

NH2

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