1. Heterocyclic Chemistry: Parts 2 and 3
Year 3, Semester 1
Dr Boa, C301, a.n.boa@hull.ac.uk
Contents Overview
Part 2
1. HETEROCYCLES - INTRODUCTION
2. QUINOLINES & QUINOLONES
3. ISOQUINOLINES
4. INDOLES
5. MISC. HETEROCYCLES & MID COURSE REVIEW
Part 3
1. 1,3-DIPOLAR CYCLOADDITION REACTIONS - INTRODUCTION
2. ISOXAZOLES AND ISOXAZOLINES
3. ISOXAZOLIDINES
4. DIAZOLES AND TRIAZOLES
5. COURSE REVIEW
Suggested reading
• Organic Chemistry, 1st Ed., J. Clayden, N. Greeves, S. Warren and P. Wothers,
OUP. Chapters 42, 43 and 44 (sections thereof).
• Aromatic Heterocyclic Chemistry, D.T. Davies, OUP, QD 400 D2
• Heterocyclic Chemistry, T.L. Gilchrist, QD 400 G5
• Heterocyclic Chemistry, J.A. Joule, K. Mills and G.F. Smith, QD 400 J8
Learning outcomes:
At the end of the course you should be able to:
1. Identify, draw and be familiar with the names of the classes of heterocyclic
molecules covered in the course (not detailed nomenclature)
2. Distinguish between cyclisation and cycloaddition reactions and describe the
general features of each class
3. Formulate products arising from cyclisation and cycloaddition reactions. I.e. work
out what heterocycle is produced from a given set of reagents (including methods
for making 1,3-dipoles)
4. Apply the ring modification reactions covered to given heterocycles
5. Give synthetic sequences for the syntheses covered (identify intermediates)
6. Describe the influence of reaction conditions on product (isomer) distribution
7. Explain isomer distribution in cyclisation reactions in terms of thermodynamic and
kinetic effects.
8. Describe the effect of ring substituents on rates of cyclisation reaction and isomer
distribution.
For a full set of notes and sample past paper questions (some with solutions) see
http://www.hull.ac.uk/php/chsanb/teaching.html

25. HETEROCYCLE PROBLEMS
Formulate the products from the following reactions, all of which are the Doebner-von Miller
variation of the Skraup quinoline synthesis.
H
1 +
H3 C O ?
NH2
Br H
2 + ?
O
H2 N Ph
CH3
3 + ?
CH3 H3C O
NH2
O
Br
4 H ?
+
NH2 Ph
O
5 Ph
+ ?
NH2
CH3
Et
Et
O
NH2 +
6 Ph ?
H
F
O
Br
7 H3C ?
+
H2N
CH2CH3
Formulate the products from the following reactions, all of which are Fischer indole syntheses.
O
8
+ H3 C ?
NHNH2
O
9 ?
+ H3 C CH3
NHNH2
O
10
+ ?
NHNH2
Br O
11 + CH3CH2 CH2CH3 ?
H2NHN

26. Br O
12 + ?
H3C CH3
NHNH2
O
NHNH2
13 + ?
MeO
O
14 + ?
NHNH2 H3C Ph
CH3
O
15 + ?
CH3
NHNH2
F O
16 + ?
NHNH2
From what starting materials could you make these two indoles? Will there be any problems with
formation of isomeric products? If so what is (are) their structure(s)?
H3C
17 ? + ?
N
H
CH3
18 ? + ?
MeO N
H
Given the information provided formulate the unknown products from the following reactions.
O KOH CO2H
O EtOH-H2O
19 O +
CH3 Ph heat
N
H N Ph
O KOH
O EtOH-H2O
O + ?
CH3CH2 Ph heat
N
H
CH3
H3C 1. AcOH, 40 oC,
with azeotropic
1. 150 oC removal of H2O
20 NH2
2. c. H2SO4 2. Ph2O, 250 oC
? + ?
O O
Ph OEt