heterocycles 2
TRANSCRIPT
Heterocyclic Chemistry: Parts 2 and 3
Year 3, Semester 1 Dr Boa, C301, [email protected]
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
HETEROCYCLE PROBLEMS
Formulate the products from the following reactions, all of which are the Doebner-von Miller variation of the Skraup quinoline synthesis.
O
H
H3C+
NH2
1 ?
Br
H2NO
H
+
Ph
2 ?
NH2
O
CH3
H3C+CH33 ?
Br
NH2
O
H+Ph
4 ?
Et
O
Ph
CH3
+NH2
5 ?
NH2O
H+ Ph
Et
F
6 ?
O
H3C
CH2CH3
+H2N
Br7 ?
Formulate the products from the following reactions, all of which are Fischer indole syntheses.
O
H3C+NHNH2
8?
CH3
O
H3C+NHNH2
9 ?
O
+NHNH2
10?
Br
H2NHNCH2CH3
O
CH3CH2+11 ?
Br
NHNH2CH3
O
H3C+12 ?
NHNH2+
O
MeO13 ?
NHNH2Ph
O
H3C+
CH3
14 ?
NHNH2
+CH3
O
15 ?
NHNH2
+OF
16 ?
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)?
+
NHCH3
H3C17 ??
NH
MeO18 + ??
Given the information provided formulate the unknown products from the following reactions.
Ph
O
CH3CH2+
Ph
O
CH3+
N PhNH
O
O
CO2H
NH
O
O
KOHEtOH-H2O
heat
KOHEtOH-H2O
heat
CH3
19
?
NH2
1. AcOH, 40 oC, with azeotropic removal of H2O2. Ph2O, 250 oC
1. 150 oC2. c. H2SO4
Ph OEt
O O
+
H3C
20
??