About the Authors

Mohamed Hilmy Elnagdi was born in Egypt 1941. He graduated in 1962

(Cairo University) where he also worked and obtained his M.Sc. (1966) and

Ph.D. (1969) Diploma in Applied Chemistry (Japan), 1973 and D.Sc. (1982).

Degrees. He was awarded The Alexander von Humboldt Fellowship at

University of Bonn with Prof. H. Wamhoff and has several sabbatical leaves

with plenty of German scientists. He also received fellowships from several

institutions in Norway, USA and Japan. He worked at Cairo University as

Professor of Organic Chemistry since 1980 and as visiting Professor to

Kuwait University 1993-1999 and from 2003 till now. Prof. Elnagdi has

specialized in the synthesis of polyfunctional heterocycles and has several

national and regional research awards.

Kamal Usef Sadek was born in El-Minia (Egypt) and has received B.Sc.

degree (honors) in applied chemistry from Assiut University (Egypt) in

1969. He obtained his M.Sc. and Ph.D. from Cairo University. He was

appointed as demonstrator in Minia University (1970). Since then he was

appointed as Lecturer (1980), Associate Professor (1985) and full Professor

(1990). In 1987 he was awarded the Alexander von Humboldt Foundation

fellowship with Prof. W. weigrebe in Regenesburg University and has

several study leaves with Prof. M.Regitz of Kiserslautern University and

Prof. H.H. Otto of Frieburg University. Currently, he is working in

developing green technologies for the synthesis of biologically active

heterocycles.

Dr. Moustafa Sherief Moustafa was born in Egypt on July 13th 1981. He

graduated from the Faculty of Science at Cairo University in May 2002 and

in February 2012 obtained his Master degree from Kuwait University which

received the University of Kuwait Prize for the best Master thesis in the

academic year 2011-2012. Since 2005 Mr. Moustafa is working as research

assistant in the chemistry department – University of Kuwait, during his

period he published two books, three reviews and 25 research papers till

2014.

Dr. Saleh Mohammed Al-Mousawi was born in Kuwait on November 1st -

1953. He graduated from the Faculty of Science at Kuwait University in

1975 and in 1980 obtained his Ph.D. from Bristol University U.K. on

synthetic organic chemistry. Dr. Al-Mousawi Prof. Elnagdi did work all the

time in Kuwait University. He started as assistant professor in the period of

1980-2005 then associate professor till now. Dr. Al-Mousawi published 38

papers in the field of organic chemistry till 2014.

Copyright © Prof Dr Mohamed Hilmy Elnagdi, Prof Dr Kamal Usef

Sadek, Moustafa Sherief Moustafa, Dr Saleh Mohammed Al-Mousawi

(2015)

The right of Prof Dr Mohamed Hilmy Elnagdi, Prof Dr Kamal Usef

Sadek, Moustafa Sherief Moustafa, Dr Saleh Mohammed Al-Mousawi

to be identified as authors of this work has been asserted by them in

accordance with section 77 and 78 of the Copyright, Designs and

Patents Act 1988.

All rights reserved. No part of this publication may be reproduced,

stored in a retrieval system, or transmitted in any form or by any

means, electronic, mechanical, photocopying, recording, or otherwise,

without the prior permission of the publishers.

Any person who commits any unauthorized act in relation to this

publication may be liable to criminal prosecution and civil claims for

damages.

A CIP catalogue record for this title is available from the British

Library.

ISBN 978 1 84963 991 4

www.austinmacauley.com

First Published (2015)

Austin Macauley Publishers Ltd.

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Printed and bound in Great Britain

Contents

Introduction 11

Chapter 1 Nomenclature of Heterocycles 12

1. Introduction 12

Chapter 2 Aromaticity of fully Unsaturated Heterocycles and its Reflect on The

Chemical Reactivity 21

2.1. Introduction 21

2.2. Aromatic Monoheteroaromatic Fully Unsaturated Heterocycles 21

2.2.1 The Pi-excessive Molecules 22

2.2.2 Pi-deficient Molecules 22

2.2.3. The Azoles 23

2.4. Other Aromatic Systems 24

2.4.1. Monocycles 24

2.4.2. Polycycles 25

2.5. Ring Current 26

2.6. Resonance Energy Stabilization 28

Chapter 3 Chemical Reactivity of Aromatic Heterocycles 29

3. General Consideration 29

3.1. Electrophilic Substitution 29

3.2. Typical Reactivity Pattern of Aromatic Heterocycles with Electrophiles 34

3.2.1. Halogenation 34

3.2.2. Nitration 37

3.2.3. Alkylation; Acylation; Mannich like and Michael Addition like Reactions 40

3.2.3.1 Alkylation 40

3.2.3.2. Acylation 50

3.2.4 Coupling with Aromatic Diazonium Salts 52

3.3. Reactivity of Heteroaromatics Towards Nucleophilic Reagents 53

3.4. Amination (The Chichibabin Aminatian) 59

3.5. Photochemistry of Heterocyclic Compounds 63

3.6. Thermal Cycloaddition and Precyclic Reactions 73

Chapter 4 Functional Group Reactivity 87

4.1. Alkyl, Alkenyl Functions 87

4.1.1. Reactivity of π-deficient Heterocycles 87

4.1.2. Reactivity of π-excessive Heterocycles 93

4.2. Reactions with Nucleophilic Reagents 101

4.3. Oxygen Containing Functional Groups 102

4.4. Heteroaromatics Amines 107

Chapter 5 Synthesis of Heterocycles 115

5. Heteroaromatics 115

5.1. Introduction 115

5.1.1. Intramolecular Condensation 115

5.1.2. Addition, Condensation and Condensation Addition Routes 142

5.1.3. Synthesis of Heterocycles via Pericyclic Reactions 148

5.1.3.1 Cycloadditions 148

5.1.3.2. Electrocyclic Reaction 149

5.1.3.3. Sigmatropic Rearrangements 150

5.1.3.4 Cheletropic Reactions 150

5.1.4. Rules for Electrocyclic Reactions 154

5.1.5. Dipolar Additions 156

5.1.6. Reactions Leading to Interesting Heteroaromatics are 157

5.1.6.2. [2+2] Cycloaddition 160

5.1.6.3. Cheleotropic Reactions 161

Chapter 6 Functionally Substituted Arylhydrazones as Precursors to Five and

Six Membered Heterocycles 163

6.1 Introduction 163

6.2 Arylhydrazones as 3 and 4 Atom Precourser to Nitrogen Heterocycles 163

6.3. Arylidenemalononitrile as Precursors to Heterocycles 166

6.4 Functionally Substituted Enamines as Versatile Reagents for Synthesis of

Polyfuntionally Substituted Heteroaromatics 167

6.5. Utility of Enaminones as Precursors to Heterocycles 169

6.6 Oxoalkano Nitriles as Precursors to Heterocycles 171

Chapter 7 Heterocycles and Life 172

7.1. Heterocycles and Life 172

7.1.1 Role of Carbohydrates in Life. 173

7.2. Steroelectronic Effects. 174

7.2.1. Carbohydrate Metabolism 175

7.3. Biosynthesis of Oxygen Heterocycles 179

7.4. Synthesis of Natural Heterocycles from Cinnamic Acid 182

7.5. Basic Chemistry behind this Synthesis and how Nature Affect That 183

7.5.1. Biosynthesis of proline 186

7.5.2. Syntheses of Adenine and Guanine197 186

7.5.3. Pyrimidine Synthesis 189

Chapter 8 Heterocycles as Dyes and Pigments 191

8.1. Introduction 191

8.2. Synthetic Heterocyclic Dyes 192

8.2.1. Azodyes 192

8.3. Heterocycles as Organic Pigments 205

8.3.1. Introduction 205

8.4. Heterocycles in High Technology Applications 207

8.4.1. Photochromic Heterocycles 207

8.4.1.1. Diheteroaryl Ethylenes 208

8.4.2. Electrocyclic Reactions of Fulgides 212

8.4.3. Spirooxazines 213

8.4.4. D2T2 Printing 214

8.4.4.1. Properties required of D2T2 Dyes 215

Chapter 9 Heterocycles as Drugs 216

9.1. Introduction 216

Chapter 10 Heterocycles as Explosives 227

10.1. Introduction 227

10.2. Pyrazoles Hide and Seek 228

10.3. 1, 3,4 Oxadiazoles 229

Chapter 11 Heterocyclization during Food Cooking 233

11.1. Caramelisation 233

11.2. Millard Reaction3 233

Chapter 12 Heterocycles as Organic Metals 238

Chapter 13 Green Synthesis of Heterocycles 241

13.1. Introduction 241

13.2. Green Chemistry Principles 241

13.3. Green Synthesis 242

13.4. Catalysts 242

13.5. Solvents 242

13.6. Multicomponent One-pot Syntheses 242

13.7. Utility of Renewable Energy Sources and Feed Stocks 242

13.8. Synthesis of Pyrans and Thiopyrans 243

13.9. Synthesis of pyridines 244

13.10. Synthesis of Pyrazolo [1, 5-a] Pyrimidines 247

I n t r o d u c t i o n

This book is based on courses we designed while teaching heterocyclic

chemistry courses in Egyptian Universities, in Libya and in Kuwait as well

as in Saudi Arabia for almost fifty years. Needless to say, that the course

material has changed several turns until we arrived at this framework.

Unfortunately all textbooks of organic chemistry and texts of chemistry

devoted to chemistry of heterocycles, with only perhaps one recent book,

describes the chemistry of only synthesized heterocycles but ignores dealing

with those made by nature, although no doubt that life only started when

algae could photosynthesise carbohydrates and the majority of these are

derivatives of either pyran or furan. r furan. In this text we will start with

chemistry of aromatic heterocycles and their nomenclature. Also a chapters

that demonstrating the existing role of heterocycles in chemical industry

basically as dye ingredients, pharmaceuticals, agrochemicals, and catalyses

as well as other less familiar purposes are cited. Then shifted to heterocycles

manufactured by nature showing how nature since life beginning managed to

synthesis heterocycles in nature simple way swiftly and at ambient

temperature. By the end the brief chapter demonstrating green synthesis of

heterocycles will be described. We hope that we will be able to come to a

modern text that encourages chemistry in structures as well as researchers to

go back to this vital field.

Prof. Dr. Mohamed Hilmy Elnagdi

Prof.Dr. Kamal Usef Sadek

Moustafa Sherief Moustafa

Saleh Mohammed Al-Mousawi

C h a p t e r 1

N o m e n c l a t u r e o f H e t e r o c y c l e s

1. Introduction

At the early days of heterocyclic chemistry no one predicted the potentiality of

this science and heterocycles at these days were given names indicating origin

like caffeine (1) extracted from coffee or and pyrrole (discovered in 1857) from

pyrolysate of bone and the name was derived from the Greek word that means

red referring to its color.

N

NN

N O

O

CH3

CH3

H3C

NH

PyrroleCaffeine

1 2

After a short period the need for systematic nomenclature become apparent

and Hanzsch1 and Widman

2 have independently suggested the nomenclature

system that carry their names. The IUPAC nomenclature still approves this

method and the trivial names for ring systems shown in chart 1 were also

approved.3

1 A. Hantzsch and J.H. Weber, Ber. Dtsch. Ges. 20 , 3228 (1887).

2 O. Widman, J. Prakt. Chem. 38 , 185 (1888).

3 IUPAC Nomenclature of Organic Chemistry, Definitive Rules, Sections A to H, Pergamon

Press, Oxford, 1979.

O S Se Te

Furan Thiophene Selenophene Tellurophene

N

NH

NO

NO

NNH

PyrroleIsoxazoleFurazane1H-imidazole

N

N

NN

O NH

N

Pyrazine Pyridazine 4H-pyrane Pyrazole

N

N NH

N

SN

N N

N

Purine Isothiazole Pyridine Pyrimidine

S NH

2H-Thiopyrane Indole

NH

Isoindole

NH

N

1H-Indazole

N

N

Quinazoline

NN

Cinnoline

N

Quinoline

N

N

Phthalazine

NH

Piperidine

NH

HN

Piprazine

O

HN

Morpholine

N

Isoquinoline

O

Chromene

N

N

N

N

Pteridine

NH

Pyrrolindine

1.1. The Hanzsch and Widman Nomenclature

The rules used are:

1- The name of the ring is derived by placing a prefix to indicate the

heteroatom or heteroatoms in the ring and a suffix that indicates the ring

size. In the table 1 and 2 are listed the approved prefixes and suffixes4.

Examples:

O O

Oxol Oxolane

NH

Azolidine

O

Oxiran

O

Oxirine

Table 1: Prefixes for noncarbon elements

Element Valence Prefix

Flour (F) 1 Flour

Chlore (CI) 1 Chlora

Bromine (BR) 1 Broma

Iodine (I) 1 Ioda

Oxygen (O) 2 Oxa

Sulphur (S) 2 Thia

Selenium (Se) 2 Selena

Tellurium (Te) 3 Tellura

Nitrogen (N) 3 Aza

Phosphorous

(P)

3 Phospha

Arsenic (As) 3 Arsa

Antimony (Sb) 3 Stilba

Bismuth (Bi) 3 Bisma

Silicon (Si) 4 Sila

Germoium (Ge) 4 Germa

Tin (Sn) 4 Stanna

Lead (Pb) 4 Plumba

Boron (B) 3 Bora

Mercury (Hg) 2 Mercura

4 IUPAC Commission on Nomenclature of Organic Chemistry, Pure & Appl. Chem. 55, 409

(1983).

2. If the ring contains more than one heteroatom of the same type the term

di, tri. and tetra. etc... is used to indicate the number of these atoms and

allocate number is used to indicate their place in the ring. The

heteroatom that would give next heteroatom and/or substituent least

number is given number l. Example:

N

NH

HO2C

1,3-Diazole-4-carboxylic acid

1

2

34

5

Table 2: Systems for Hantzsch-Widman names

Ring

Size

Rings Containing Nitrogen Rings Containing No Nitrogen

Unsaturated Saturated Unsaturated Saturated

3

4

5

6*

7

8

9

10

Irine

Ete

Ole

Ine

Epine

Ocine

Onine

Ecine

Iridine

Eidine

Olidine

Ane**

****

****

****

****

Irene

Ete

Ole

Ine

Epine

Ocine

Onine

Ecine

Irane

Etane

Olane

Inane***

Epane

Ocane

Onane

Ecane

* suffixes irine and irane are used for rings in which the last named element

is F, Cl, I, O, As, or Sb.

** For rings in which the last named element is O, S, Se, Te, Bi, or Hg.

*** For rings in which the last named element is N, Si, Sn, Pb or B

**** Expressed by prefixing perhydro before name of unsaturated.

3. If two or more different heteroatoms are present, the one in higher place

in table 2 is indicated firstly and counting ring corners should start from

this atom then goes in the direction that gives the next atom the least

possible number. Example:

N O

Cl

5-Chloro-1,3-oxazole

1

2

3

4 5

4. if trivial names are used for naming rings having sp3 atom, H location

should be used to indicate this atom.

NH

NN

NH

1H-Pyrrole 4H-Pyrazole 1H-Indole

5. If the heterocyclic ring has an alkyl and halide substituent in case of

existence of a choice, counting should go in the direction that gives the

least number for either. Example:-

NH

Cl

H3C

2-Chloro-4-methyl-1H-pyrrole

6. If the hetero rings carry a substituent other than alkyl and halide, the

ring is considered as a derivative of this function. Examples:-

NNH

H2N

ON

CO2H

1H-Pyrrole-4-amine Isoxazole-3-carboxylic acid

7. If the heterocyclic ring is carrying more than one substituent the

substituent of highest priority is taken as the parent. Example:-

SN

CO2EtH2N

Ethyl 4-aminoisoxazole-3-carboxylate

1.2. IUPAC Nomenclature

According to the IUPAC rules, an organic compound must be allocated to the

first appropriate class of compounds in the following list to which it belongs.

The classes are arranged in order of decreasing priority:

a. Cation and anions

b. Acids: carboxylic, peroxycarboxylic, thiocarboxylic, sulfonic,

Sulfinic,...etc

c. Derivatives of acids: anhydrides, esters, acyl halides, amides,

hydrazides, imides, amidines, ...etc.

d. Nitriles: (cyanides), isocyanides.

e. Aldehydes, thioaldehydes and their derivatives.

f. Ketones, thioketones and their derivatives.

g. Alcohols, phenols, thioles and their ester derivatives with inorganic

acids

h. Hydroperoxides.

i. Amines, imines and hydrazines

j. Ethers, thioethers.

k. Peroxides

All other functional groups which are included in one of these classes are

then written as prefixes in the form of the name in alphabetic order.

Fusion names

1- The monocyclic components of fused systems are firstly defined.

Approved trivial names should be used, and if not available the

Hantzsch-Widman names should be used.

N

Na

b

c

d

e

f

1 5

4

32

N

Na

bc

d

e f

HN1

5

4

32

Pyrrolo[1,2-a]pyrimidine

2. The larger ring is chosen as parent so long as it contained nitrogen,

if not choose the ring having a heteroatom which ranks highest in

Table 2.

3. The name of the daughter ring is written first and the ending (e) is

replaced by parent ring (or some rings are further abbreviated (cf.

list). Brackets [ ] are placed between the daughter ring name and

parent one.

a

b

c

ef 1 5

4

32

Pyrrolo[1,2-a]pyrimidine

d

Some prefixes are further appreciated, as exemplified in the following list

Acenaphthylene Acenaphtho

Anthracene Anthra

Benzene Benzo

Furan Furo

Imidazole Imidazo

Isoquinoline Isoquino

Naphthalene Naptho

Perylene Perylo

Pyridine Pyrido

Pyrimidine Pyrimido

Quinoline Quino

Thiophene Thieno

4. The corners of the daughter ring are given as numbers while that of

the parent are indicated by letters.

5. The position of a junction is now defined by citing between

brackets the numbers of the smaller ring then letters of the parent

ring. The number met firstly while counting the parent is written

firstly.

N

N

NH

N

2H-Pyrazolo[3,4-d]pyrimidine

N

N

NNH

1H-Pyrazolo[4,5-d]pyrimidine

N

NN

N

Pyrazolo[5,1-c]triazine

6. Counting the ring as a whole should start from a position adjacent

to the ring junction. The best way to do this is to place, as many

rings as possible in one line and extract rings should be placed up

on the right hand and in a way that enables giving the least possible

numbers to heteroatoms when counting starts from the most

anticlockwise position and continues clockwise.

NH

N

N

1 2

3

4

5

5H-Pyrimido[5,4-b]indole

7. If fusion has occurred between two five membered rings containing

nitrogen, the one with heteroatom of highest priority is considered

parent.

Pyrano[2,3-c]pyrazole

N

NO

N

ON

Imidazo[2,1-b]oxazole

8. If both ring components contained the same atoms, the ring with

least separation between heteroatoms is considered parent.56

5 A.D. McNaught and P.A.S. Smith, Comprehensive Heterocyclic Chemistry, A.R. Katritzky

and C.W. Rees Ed. Academic Press, New York, 1, 7 (1948).

NN

HN

1H-Imidazo[1,2-b]pyrazole and notPyrazolo[3,2-b]imidazole

6 IUPAC Commission on Nomenclature of Organic Chemistry “ Nomenclature of Fused and

Bridget Fused Ring Systems, Pure & Appl. Chem., 70, 143 (1998)

C h a p t e r 2

A r o m a t i c i t y o f f u l l y U n s a t u r a t e d

H e t e r o c y c l e s a n d i t s R e f l e c t o n T h e

C h e m i c a l R e a c t i v i t y

2.1. Introduction

The term "Aromatic" was initially made to distinguish a group of coal tar

distillation products that has certain "Aromatic" oder. When it is said that a

compound is aromatic in character it is generally meant that this compound

although having multiple bonds it prefers to react by substitution rather than by

addition to keep its aromatic identity. This preference is a result of stabilization

that is inferred upon the aromatic system as a result of the existence of a

conjugated double bond system. Molecular orbital (M.O) theories predict extra

stabilization for a system that can be presented in more than one ground state

electronic distribution by moving in one plain, electrons form one part of the

molecule to the other part. According to Hückel’s systems with the number of its

π-electron equals (4n + 2) in one cycle are aromatic in character and have extra

stabilization.7

Typical for aromatic systems is benzene (6 π electrons) that can have two

contributing resonance forms (cf. 1).

1

Fully unsaturated five and six membered rings as well as some larger rings

are aromatic in the sense that they "tend" to react by substitution rather than

addition. This tendency varies from one system to other, as we will see later.

However, aromaticity in heterocycles differs than that in aromatic benzene

derivatives in several aspects. In fact we have several different situations for π

cloud distribution that differ than the case of the π cloud distribution in benzene

which is regarded as a regular hexagon with uniform distribution of π electrons

so as the share of each carbon is unity. If we considered this situation as base

then for heterocycles we have the following cases.

2.2. Aromatic Monoheteroaromatic Fully Unsaturated

Heterocycles

7 M.K. Cyranski, T.M. Krygowski, A.R. Katritzky and P. von R. Schleyer, J. Org. Chem., 67,

1333 (2002).

2.2.1 The Pi-excessive Molecules

For these rings to have aromatic stabilization, heteroatom lone pair should

participate to the resonance and as a result of this participation charge separated

forms with -Ve charges residing at carbon corners can result. (cf. scheme 1).

X X X XX

We have a situation of six electrons for five corners and thus some of these

corners should have more than of unit electrons and for this reason these

molecules are called pi-excessive molecules. This ground state electronic

distribution. M.O. calculations for furan (2) and pyrrole (3) indicate that the ring

corners are electron rich as compared to those of benzene.8 9 10

O NH

2 3

1.10

1.09

1.61

1.07

1.08

1.71

2.2.2 Pi-deficient Molecules

While the two resonating forms 4 and 5 are similar to those of benzene, the

heteroatom electronegative element tends to withdraw electrons from ring

carbons and the carbons and to heteroatoms are thus pi-deficient.

In Scheme 2 the resonating forms for pyridine, as typical example are shown.

Results of M.O. calculations of π electron density in pyridine and pyrimidines

are also shown (cf, 6 and 7).11

12

8 For a review see: A.R. Katritzky , Handbook of Heterocyclic Chemistry, Pergamon Press,

Oxford, UK, pages 58, 571, (1985). 9 C.W. Bird, Tetrahedron , 42, 89 (1986).

10 P. von R. Schleyer, C. Maerker, A. Dransfeld, H. Jiao and N.J.R. von Hommes, J. Am.

Chem. Soc. 118, 6317 1996. 11 For a review see: L.I. Belen,kii, V.N. Gramenitskaya, The Literature of Heterocyclic

Chemistry, Part VIII, 1999-2001 “Adv. In Heterocyclic Chem, 87, 1, (2004). 12 For a reiew see: L.D. Quin and J.A. Tyrell, Fundamental of Heterocyclic Chemistry, Jown

Wiley & Sons Inc. Chapter 7, 131 (2010).

X X

4 5

N N N N N

N N

N

6 7

1.225

0.729

0.803

1.1370.866

1.064

0.932

1.166

Scheme 2

2.2.3. The Azoles

The term azole has been developed to refer to five membered heterocycles in

which one or more carbons of the carbon corners of a monoheteroatomic

heterocycles is replaced by nitrogen. There are generally two families 1,2-azoles

(8) and 1,3-azoles (9).

NX N X

8 9

1

2

3

4 5

1

2

3

4 5

In both systems while atom X donates electrons to the system ring carbon

to the heteroatom in electron rich (C-4 in 8and 9), nitrogen atom with its fixed

lone pair withdraw electrons from carbons and with respect to it. (Scheme 3

and 4). This will also have its reflect on the physical properties and the chemical

reactivity pattern of these molecules.13

13 Z. Chen, C.S. Wannere, C. Combinboeuf, R. Puchta and P. von R. Schleyer, Chem. Rev.,

105, 3842 (2005).

NX

N X N X N X N X

NX

NX

NX

2.4. Other Aromatic Systems

2.4.1. Monocycles

According to Hückel rule any monocyclic system with 4n+2π electrons would

be aromatic. Thus we may go to the extreme that O3 (X = Y = Z=O) & N3 (X =

Y = Z = NH) may be aromatic. However, ozone is acyclic system and also

triazidine is predicted to have open structure. This is due to the fact that in (10)

the lone pairs are not planner.14

In four membered rings only dithiete ring (X =

Y = S) (11) seems to be stable than open chain isomer.15

If we look at larger rings, the nine membered ring 12 and eight membered

ring 13 seems to be aromatic unless R substituent is electron attracting. The aza

annulene 14 is planner and NMR indicates its aromaticity.16

17

X

Z Y

10

YX

11

N

18

N

9

N N

12 13 14

RR

R

14 C. Leuenberger, L. Hoesch and A.S. Dreiding, J. Chem. Soc., Chem. Commun., 1197

(1980). 15 J.D. Goddard, J. of Computational Chemistry, 8, 389 (1987). 16 M. Breuninger, R. Schwesinger, B. GallenKamp, K.-H. Muller, H. Fritz, D. Hunkler and H.

Prinzbach, Chem. Ber. , 131, 3161 (1980). 17 W. Gilb and G. Schroder, Chem. Ber., 115, 240 (1982).

2.4.2. Polycycles

a) Benzofused heterocycles:

Although benzofused heterocycles show bond alternations corresponding to

kekule structures (15-24), like naphthalene they prefer to react by substitution

rather than by addition while other criteria indicate that they can generally be

considered aromatics.

NN

NN

NN

N

NH

O S NH

N

NH

N

N

N

N

15 16 17 18 19

20 21 22 23 24

b) Other polycyclic systems:

Large number of 10π electron systems can be drawn by fusion of two

heteroaromatic rings. At least systems (25-28) are planner and behave like

aromatic compounds. Even when ring junction is nitrogen, (29-31) the systems

are still aromatic.