Post on 17-Jul-2016
description
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.
25 Canada Square
Canary Wharf
London
E14 5LB
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.