Supplements to the 2nd Edition of

RODD'S CHEMISTRY

OF C A R B O N

COMPOUNDS

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Supplements to the 2nd Edition o f

RODD'S CHEMISTRY

OF

CARBON COMPOUNDS
VOLUME I

ALIPHATIC COMPOUNDS
,k

V O L U M E II

ALICYCLIC COMPOUNDS

V O L U M E III

AROMATIC COMPOUNDS

,k

V O L U M E IV

HETEROCYCLIC COMPOUNDS

VOLUME V

MISCELLANEOUS
GENERAL INDEX
,A,

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Supplements to the 2nd Edition [Editor S. Coffey) of

RODD'S C H E M I S T R Y OF
CARBON COMPOUNDS
A modern comprehensive treatise
Edited by
MARTIN F. ANSELL
Ph.D., D.Sc. (London) F.R.S.C.C. Chem.
Reader Emeritus, Department of Chemistry,
Queen Mary College, University of London, Great Britain
Supplement to
VOLUME IV HETEROCYCLIC COMPOUNDS
Part G:
Six-Membered Heterocyclic Compounds with a Single Nitrogen Atom
in the Ring to which are Fused Two or More Carbocyclic Ring Systems,

and Six-Membered Ring Compounds where the Hetero-Atom is
Phosphorus, Arsenic, Antimony or Bismuth. Alkaloids Containing a
Six-Membered Heterocyclic Ring System

ELSEVIER
Amsterdam - Oxford - New York - Tokyo 1987

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Distributors for the United States and Canada:
ELSEVIER SCIENCE PUBLISHING COMPANY INC.
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New York, NY 10017

Library of Congress Card Number: 64-4605
ISBN 0-444-42897-6
9 Elsevier Science Publishers B.V., 1987
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 written permission of the publisher, Elsevier Science Publishers
B.V./Science & Technology Division, P.O. Box 330, 1000 AH Amsterdam, The Netherlands.
Special regulations for readers in the USA m This publication has been registered with the
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from the CCC about conditions under which photocopies of parts of this publication may be
made in the USA. All other copyright questions, including photocopying outside of the USA,

should be referred to the publisher.
No responsibility is assumed by the Publisher for any injury and/or damage to persons or
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VI
CONTRIBUTORS TO THIS VOLUME
Kenneth W. Bentley, M.A., D.Sc., D.Phil., F.R.S.E.
Department of Chemistry, Loughborough University,
Loughborough, Leicestershire LEII 3TU
John D. Hepworth, B.Sc., Ph.D., C.Chem., F.R.S.C.
Department of Chemistry, Lancashire Polytechnic,
Preston, Lancashire, PRI 2TO,
Robert Livingstone, B.Sc., Ph.D., F.R.S.C.
Department of Pure and Applied Chemistry, The Polytechnic,
Queensgate, Huddersfield, HDI 3DH
A. Reginald Pinder, D.Sc., Ph.D., D.Phil.
Department of Chemistry, The University,
Clemson, South Carolina, U.S.A.
Malcolm Sainsbury, D.Sc., Ph.D., C.Chem., F.R.S.C.
Department of Chemistry, The University,

Bath, BA2 7 A Y
Raymond E. F a i r b a i r n ,
B.Sc., Ph.D., F.R.S.C.
F o r m e r l y of R e s e a r c h D e p a r t m e n t ,
Dyestuffs Division,
i.c.i.
(INDEX)

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VII
PREFACE

TO S U P P L E M E N T

IVG

The p u b l i c a t i o n of this v o l u m e c o n t i n u e s the s u p p l e m e n tation of the s e c o n d e d i t i o n of Rodd's C h e m i s t r y of C a r b o n
Compounds, thus k e e p i n g this m a j o r w o r k of r e f e r e n c e u p - t o date.
In this v o l u m e C h a p t e r s 28 to 35 of the s e c o n d e d i t i o n
are b r o u g h t u p - t o - d a t e and the s u p p l e m e n t covers the advances
that have o c c u r r e d in the decade since the p u b l i c a t i o n of
Volume IVG in 1978.
I have been f Q r t u n a t e in that three of the c o n t r i b u t o r s
to the s e c o n d edition, n a m e l y P r o f e s s o r Bentley, P r o f e s s o r
P i n d e r and Dr S a i n s b u r y have again p r o v i d e d v a l u a b l e contributions, as have Dr H e p w o r t h and P r o f e s s o r L i v i n g s t o n e
who have p r e v i o u s l y c o n t r i b u t e d to o t h e r s u p p l e m e n t s to Rodd.
To each of these authors I express my thanks and a p p r e c i a t i o n
for p r o v i d i n g clear, c o n c i s e and i n t e r e s t i n g chapters.

I
also w i s h to thank Dr F a i r b a i r n , who i n d e x e d the second
edition, for again p r o v i d i n g an e x t r e m e l y d e t a i l e d index
w h i c h g r e a t l y f a c i l i t a t e s the use of this book.
At a time w h e n there are many s p e c i a l i s t reviews, monographs and reports available, there is still in my view an
i m p o r t a n t place for a book such as Rodd, w h i c h gives a
b r o a d e r c o v e r a g e of o r g a n i c chemistry.
One aspect of the
value of this w o r k is that it allows the expert in one field
to q u i c k l y find out what is h a p p e n i n g in o t h e r fields of
chemistry.
On the other h a n d a chemist l o o k i n g for the way
into a field of study will find in Rodd an o u t l i n e of the
i m p o r t a n t aspects of that area in c h e m i s t r y t o g e t h e r w i t h
l e a d i n g r e f e r e n c e s to other works to p r o v i d e more d e t a i l e d
information.
This volume has been p r o d u c e d by direct r e p r o d u c t i o n of
the m a n u s c r i p t s .
I am most grateful to the c o n t r i b u t o r s for
all the care and effort b o t h they and their s e c r e t a r i e s have
put into the p r o d u c t i o n of the m a n u s c r i p t s , i n c l u d i n g the
diagrams.
I also w i s h to thank the staff at E l s e v i e r for all
the help they have given me and for seeing the t r a n s f o r m a t i o n
of authors' m a n u s c r i p t s to p u b l i s h e d work.

September

1987


Martin

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Ansell


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IX

CONTENTS
V O L U M E IV G
Heterocyclic Compounds: Six-Membered Heterocyclic Compounds with a Single Nitrogen Atom
in the Ring to which are Fused Two or More Carbocyclic Ring Systems, and Six-Membered
Ring Compounds where the Hetero-Atom is Phosphorus, Arsenic, Antimony or Bismuth.
Alkaloids Containing a Six-Membered Heterocyclic Ring System
Preface ....................................................................................................................
Official publications; Scientific journals and periodicals .......................................
List of common abbreviations and symbols used ..................................................

Vll
XIII
XIV

Chapter 28. Polycyclic Compounds Comprising a Pyridine and Two or More
Carbocyclic Rings

by J.D. H E P W O R T H
1.

2.

3.

4.

5.

6.

7.

Acridine and its derivatives ...........................................................................
(i) Acridines, l - - (ii) 9,9'-Biacridines, 12 m (iii) Reduced acridines,
14 - - (iv) Acridones, 20 - Phenanthridine and its derivatives ................................................................
(i) Phenanthridines, 31 m (ii) Phenanthridinium salts, 35 m (iii)
Reduced phenanthridines, 38 m (iv) Phenanthridones, 4 0 Benzoquinolines .............................................................................................
(i) Benzo[f]quinolines, 4 8 ~ (ii) Benzo[g]quinolines, 5 3 (iii)
Benzo[h ]quinolines, 58 - - (iv) Benzo[d,e]quinolines, 65 - Benzoisoquinolines ........................................................................................
(i) Benzo[f]isoquinolines, 7 0 - (ii) Benzo[g]isoquinolines, 7 4 - (iii)
Benzo[h ]isoquinolines, 76 - - (iv) Benzo[d,e]isoquinolines, 78 - Benzacridines .................................................................................................
(i) Benz[a]acridines, 81 - - ( i i )
Benz[b]acridines, 8 3 (iii)
Benz[c]acridines, 8 5 (iv) Dibenzo[a,c]acridines, 9 0 (v)
Dibenzo[a,j]acridines
and dibenzo[a,i]acridines,
90 - (vi)

Dibenzo[c,h ]acridines, 91 m
Benzophenanthridines ....................................................................................
(i) Benzo[c]phenanthridines, 9 4 - (ii) Benzo[a]phenanthridines and
benzo[b]phenanthridines, 9 9 - - (iii) Benzo[i]phenanthridines, 100
(iv) Benzo[k]phenanthridines, 101 - Naphthoquinolines and naphthoisoquinolines ..............................................
(i) Naphtho[2,3-g]quinolines, 103 - - (ii) Naphtho[2,l-f]quinolines, 103
- - (iii) Naphtho[l,2-h]quinolines, 106 - - (iv) Naphtho[2,1-f]isoquinoline, 106m (v) Naphtho[l,2-h]isoquinolines, 108 - - (vi)
Naphtho[2,3-h ]isoquinolines, 108 - - (vii) Naphtho[ 1,8-fg]quinolines,
109

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30

48

70

80

93

102


X

Chapter 29. Six-Membered Heterocycles Containing Phosphorus, Arsenic,
Antimony, and Bismuth as a Single Heteroatom
by R. L I V I N G S T O N E

Introduction ...................................................................................................
Phosphorus c o m p o u n d s .................................................................................
(a) P h o s p h o r i n a n e ( p h o s p h a c y c l o h e x a n e , h e x a h y d r o p h o s p h a b e n z e n e ) and
its derivatives .........................................................................................
(i) Phosphorinanes, 111 m (ii) P h o s p h o r i n a n o n e s , 116 m (iii)
Phosphorinanols, 1 1 9 m
(b) D i h y d r o - a n d t e t r a h y d r o - p h o s p h o r i n s ...................................................
(c) Phosphorins, phosphabenzene, p h o s p h i n i n e .........................................
(d) P h o s p h i n o l i n e s a n d d i b e n z o p h o s p h o r i n s ..............................................
(i) Phosphinolines, phosphanaphthalenes, benzophosphorins, 135 ~ (ii)
Dibenzo[b,e]phosphorins (9-phosphaanthracenes), 141 ~ (iii) Dibenzo[b,d]phosphorins
(9-phosphaphenanthrene),
144
~
(iv)
P h o s p h a p h e n a l e n e derivatives, 145
Arsenic c o m p o u n d s ........................................................................................
(a) Arsabenzene (arsenin) and its derivatives ..............................................
(i) Arsabenzenes, 146 m (ii) Derivatives of arsabenzene possessing a
functional group, 150
(b) Arsanaphthalenes (benzoarsenins) .........................................................
(c) D i b e n z o a r s e n i n s .....................................................................................
(i)
Dibenzo[be]arsenins
(arsaanthracenes),
157
~
(ii)
Dibenzo[bd]arsenin, 160
(d) Miscellaneous heterocycles containing an arsabenzene ring ..................

A n t i m o n y c o m p o u n d s ....................................................................................
(a) M o n o n u c l e a r c o m p o u n d s .......................................................................
(b) Fused ring c o m p o u n d s ...........................................................................
Bismuth c o m p o u n d s .......................................................................................

1.

2.

3.

4.

111
111
111

120
122
135

146
146

156
157

161
162
162

164
166

Chapter 30. Pyridine and Piperidine Alkaloids
by M. S A I N S B U R Y
~

2.
3.
4.
5.
6.
7.
8.
9.
10.

11.
12.

Alkaloids from the Achillea and Piper genera .......... ......................................
Miscellaneous N-acylpiperidine alkaloids ......................................................
Sedum alkaloids ..............................................................................................
The alkaloids of Prosopis and Cassia species .................................................
Alkaloids of tobacco .......................................................................................
Alkaloids from p a p a y a ...................................................................................
Nuphar alkaloids ..................................................................... . ............... ........
Miscellaneous piperidines and pyridines f r o m plant sources ........................
Fungal metabolites .........................................................................................
Piperidine and pyridine bases from insects ...................................................

(a) Ant v e n o m s ............................................................................................
(b) Bases from bugs and beetles .............................................................. . ....
The p u m i l o t o x i n s ...........................................................................................
Pyridines from m a r i n e organisms ..................................................................

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169
173
174
179
183
185
187
189
197
199
199
202
203
207


XI

Chapter 31. The Quinoline Alkaloids
by M. S A I N S B U R Y
1.
2.


3.

K n o w n q u i n o l i n e s from m i c r o - o r g a n i s m s a n d higher plants .........................
N e w a l k a l o i d s .................................................................................................
(a) S i m p l e q u i n o l i n e s a n d 4 - q u i n o l i n o n e s ...................................................
(b) 2 - Q u i n o l i n o n e s .......................................................................................
(c) N e w f u r o q u i n o l i n e a n d d i h y d r o f u r o q u i n o l i n e a l k a l o i d s .......................
N o n - r u t a c e o u s m i s c e l l a n e o u s a l k a l o i d s .........................................................

209
217
217
222
235
243

Chapter 32. The Acridine Alkaloids
by M. S A I N S B U R Y
1.
2.

N e w a l k a l o i d s .................................................................................................
A c r o n y c i n e d i m e r s a n d t r i m e r s ......................................................................

247
257

Chapter 33. The Isoquinoline Alkaloids
by K.W. B E N T L E Y
1.

2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.

S i m p l e i s o q u i n o l i n e s , d i h y d r o - a n d t e t r a h y d r o i s o q u i n o l i n e s ........................
B e n z y l i s o q u i n o l i n e s .......................................................................................
B i s b e n z y l i s o q u i n o l i n e s ...................................................................................
C u l a r i n e s ........................................................................................................
A p o r p h i n e s .....................................................................................................
P a v i n e s a n d i s o p a v i n e s ..................................................................................
B e n z o p y r r o c o l i n e s ..........................................................................................
B e r b e r i n e s a n d t e t r a h y d r o b e r b e r i n e s .............................................................
A z a b e r b e r i n e s .................................................................................................
S e c o b e r b e r i n e s ................................................................................................

P r o t o p i n e s ......................................................................................................
P h t h a l i d e i s o q u i n o l i n e s ...................................................................................
S p i r o b e n z y l i s o q u i n o l i n e s ...............................................................................
I n d a n o b e n z a z e p i n e s .......................................................................................
R h o e a d i n e s .....................................................................................................
O t h e r m o d i f i e d b e r b e r i n e s .............................................................................
B e n z o p h e n a n t h r i d i n e s ....................................................................................
I p e c a c u a n h a alkaloids ....................................................................................
P h e n y l e t h y l i s o q u i n o l i n e s ...............................................................................
C o l c h i c i n e a n d its a n a l o g u e s ..........................................................................

259
265
271
280
283
295
297
298
306
307
311
313
318
321
326
328
332
340
344

345

Chapter 34. Diterpenoid Alkaloids
by A.R. P I N D E R
I n t r o d u c t i o n ...................................................................................................
X - r a y d i f f r a c t i o n analysis ...............................................................................
Mass s p e c t r o m e t r y ..........................................................................................
N m r s p e c t r o s c o p y ...........................................................................................
(a) P r o t o n m a g n e t i c r e s o n a n c e s p e c t r o s c o p y ..............................................
(b) C a r b o n - I 3 m a g n e t i c r e s o n a n c e s p e c t r o s c o p y ........................................

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349
350
353
356
356
357


XII

Chapter 35. Steroidal Alkaloids
by A.R. P I N D E R
I n t r o d u c t i o n ...................................................................................................

1.

Apocynaceae a l k a l o i d s ....................................................................................

(a)
(b)
(c)
(d)
(e)

2.
3.
4.
5.

6.

7.
8.
9.

3 - A m i n o s t e r o i d s .....................................................................................
2 0 - A m i n o s t e r o i d s ...................................................................................
3 , 2 0 - D i a m i n o s t e r o i d s ............................................................................
3 - A m i n o c o n a n i n e s ( c o n e s s a n e s ) ............................................................
M i s c e l l a n e o u s a l k a l o i d s ..........................................................................
Salamandra a l k a l o i d s .....................................................................................
Buxus a l k a l o i d s ...............................................................................................
Pachysandra a l k a l o i d s ....................................................................................
Solanum a l k a l o i d s ..........................................................................................
(a) S p i r o s o l a n e a l k a l o i d s ..............................................................................
(b) A l k a l o i d s r e l a t e d to 2 0 - p i p e r i d y l - 5 a - p r e g n a n e ......................................
(c) A l k a l o i d s r e l a t e d to 2 2 - p y r r o l i d y l - 5 c ~ - p r e g n a n e .....................................
(d) A l k a l o i d s c o n t a i n i n g a n i n d o l i z i d i n e u n i t ..............................................

(e) M i s c e l l a n e o u s a l k a l o i d s ..........................................................................
Veratrum a n d Fritillaria a l k a l o i d s ..................................................................
(a) P i p e r i d y l p r e g n a n e a n d i n d o l i z i d i n e a l k a l o i d s ........................................
(b) C - N o r - D - h o m o s t e r o i d a l a l k a l o i d s ..........................................................
(i) A l k a m i n e s , 415 m (ii) E s t e r - a l k a l o i d s , 4 1 9
Asclepiadaceae a l k a l o i d s .................................................................................
M i s c e l l a n e o u s s t e r o i d a l a l k a l o i d s ...................................................................
B i o s y n t h e s i s o f s t e r o i d a l a l k a l o i d s .................................................................

I n d e x .......................................................................................................................

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393
394
394
395
396
397
399
399
402
405
406
406
408
409
411
412
413

413
415
420
421
423
429


XIII
O F F I C I A L PUBLICATIONS
B.P.
F.P.

British
French

(United
Patent

G.P.

German

Patent

Sw.P.
U.S.P.
U.S.S.R.P.
B.I .O.S.


Swiss Patent
United States
Patent
Russian
Patent
British
Intelligence
Objectives
Sub-Committee
Reports
Field
Information
Agency, Technical
Reports
of U.S. Group Control
Council
for Germany
British
Standards
Specification
American Society
for Testing
and .~aterials
American Petroleum
Institute
Projects
Colour
Index Number of Dyestuffs
and Pigments


F.I.A.T.
B.S.
A.S.T.M.
A.P.I .
C.I.

SCIENTIFIC

Kingdom)

Patent

JOURNALS AND PERIODICALS

With few obvious
and self-explanatory
abbreviations
used in references
to
comprising
the extensive
literature
are those used in the World List
of

modifications
the
journals
and periodicals
on o r g a n i c

chemistry,
Scientific
Periodicals.

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XIV

LIST

A
Ac
a

as, asymm.
at
B
Bu
b.p.
C, mC and UC
c, C
C.D.
conc.
crit.
D
D
D
DL


d
dec. or
deriv.
E
E 1 , E2
ElcB
e.s.r.
Et
e

f
f.p.
G
g.I .c.

g
H

h
Hz
I
i.r~
J
K

kJ

decomp.

OF


COMMON
ABBREVIATIONS
SYMBOLS
USED

AND

acid
~ngstr6m units
acetyl
axial;
antarafacial
asymmetrical
atmosphere
base
butyl
boiling
point
curie,
millicurie
and microcurie
concentration
circular
dichroism
concentrated
critical
-18
Debye
unit,

1 x I0
e.s.u.
dissociation
energy
dextro-rotatory;
dextro
configuration
optically
inactive
(externally
compensated)
density
with decomposition
derivative
energy;
extinction;
electromeric
effect;
Entgegen
(opposite)
configuration
uni- and bi-molecular
elimination
mechanisms
unimolecular
elimination
in conjugate
base
electron
spin resonance

ethyl
nuclear
charge;
equatorial
oscillator
strength
freezing
point
free energy
gas liquid
chromatography
spectroscopic
splitting
factor,
2.0023
applied
magnetic
field;
heat content
Planck's
constant
hertz
spin quantum
number;
intensity;
inductive
effect
infrared
coupling
constant

in n.m.r,
spectra;
joule
dissociation
constant
kilojoule

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XV

LIST

k

OF

COMMON

ABBREVIATIONS

Boltzmann
constant;
velocity
constant
kilocalories
laevorotatory;
laevo
configuration

molecular
weight;
molar;
mesomeric
effect
methyl
mass;
mole;
molecule;
metamillilitre
melting
point
mesyl
(methanesulphonyl)
molecular
rotation
Avogadro
number;
normal
nanometre
(10 -9 metre)
nuclear
magnetic
resonance
normal;
refractive
index;
principal
quantum
number


kcal
L

M
Me
m
ml
m.p.
Ms

EM~

N
nm
n.m.r.
n

0

ortho-

o.r.d.

optical
rotatory
dispersion
polarisation,
probability;
orbital

propyl
phenyl
p a r a - ; orb i t al
proton
magnetic
resonance
clockwise
configuration
counterclockwise
config. ; entropy,
of incompleted
electronic
shells;
orbital
state
uni- and bi-molecular
nucleophilic
stitution
mechanisms
internal
nucleophilic
substitution
isms

P
Pr
Ph

P
p.m.r.


R
S

SNI,

SN 2

SNi
s
sec
soln.
symm.
T
Tosyl
Trityl
t
temp.
tert .

U

u.v.
v
Z

symmetrical;
orbital;
suprafacial
secondary

solution
symmetrical
absolute
temperature
p-tol uen e sul phonyl
triphenylmethyl
time
temperature
(in degrees
centigrade)
tertiary
potential
energy
ultraviolet
velocity
zusammen
(together)
configuration

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state

net

spin

submechan-



XVI
LIST OF COMMON ABBREVIATIONS

~A
CCE

~B
~g
l)

X ,•

(+)
(-)
(+)
0

@

,X~

optical rotation (in water unless otherwise
stated)
specific optical rotation
atomic susceptibility
electronic susceptibility
dielectric constant; extinction coefficient
microns (lO -4 cm); dipole moment; magnetic
moment
Bohr magneton

microgram (lO -6g)
wavelength
frequency; wave number
magnetic, diamagnetic and paramagnetic
susceptibilities
about
dextrorotatory
laevorotatory
racemic
negative charge
positive charge

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Chapter 28
POLYCYCLIC COMPOUNDS COMPRISING A PYRIDINE AND TWO OR
MORE CARBOCYCLIC RINGS

J.D. HEPWORTH

I.

Acridine and its derivatives

The widespread
is

reflected


chemistry
1980,

T. Brychcy,
and

Z.

in

(S.

14,

interest
the

in acridine
reviews

Skonieczny,

which

biological

Mutat.

Res., 1979, 65,
in


J.M.

their

Polak,

occurrence

Wiley,

to

1977,

activity

(A. Nasim

261 and M.R.

Science'

Chichester,

in alkaloids

their

6,


'Histochemist ry:

Horizons in Applied Biomedical
and

relate

Heterocycles,

985),

Darzynkiewicz

and its derivatives

p.

(M.F. Grundon,

and

Melamed
Widening

ed. P.J.

1981,

987


Stoward
237)

Nat.

and
Prod.

Rep., 1985, 2, 393).

(i)

Acridines

The

principal

formation
although

synthetic

route

to

of the C-9 - C-9a bond
the


exact

nature

and

acridines

7

source

to the heteroatom,
of

acridine precursor varies quite appreciably.

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involves

the

immediate


A

range


of

derivatives

obtained

by

the

acid

of

2-nitroacridine

catalysed

arylamino-5-nitrobenzaldehydes
through

protonation

of the

and J.F.K. Wilshire,
It is of interest
substituent


cyclisation

which

probably

carbonyl

Austral.

group

J. Chem.,

been
of

2-

proceeds

(J. Rosevear

1981, 34, 839).

to note that the presence

of a

meta-


arylamino moiety

leads predominantly

to the 6-substituted 2-nitroacridine;

only a small amount

of

the

in the

has

8-isomer

is

produced.

Electron

withdrawing

substituents markedly decrease the rate of cyclisation in
trifluoroacetic


acid.

groups

as

is

not

accelerates
group

has

under

the

The effect

simple,

cyclisation,
a

retarding

strongly


a

for

of electron releasing

whilst

a

dimethylamino

effect.

acidic

It

or

seems

conditions

methyl

group

a methoxy


certain

used

to

that

effect

cyclisation the amine function is protonated and perhaps
the methoxy group is similarly affected.

02N / ~ _CHO 02N~CHO
NHAr
(i) ArNH2, DMSO, Et3N ;

~ ~ /

(ii) CF3COOH

Electron rich 2-arylaminoacetophenones
alumina
1983,
the

(B. Kasum

36,


1455)

and

and

of

W.A.

amides
Denny,

cyclise readily on

Prager,

and polyphosphoric

cyclodehydration

(D. Chambers

R.H.

R

Austral.
ethyl


(I)
J.

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ester

Chem.,
effects

to 9-aminoacridines

chem.

1986, 1055).

J.

Soc.

Perkin

I,


~CONHPr
pPE

.
f


NH

NHPr

~

NO2

N(CH2CH 20Ac ) 2

(AcOCH2CH2 ) 2N~

NO2

(1)

3-Acyl- 2,5-bis (arylamino) -I, 4-benz oquinones
cyclisation

in

either

sulphuric

acid

(2)


or

undergo

methanolic

hydrogen chloride to yield acridinequinones (3) (K. Joos,
M. Pardo and W. Schafer,
4901).

J. chem. Research

(M), 1978,

2-Methoxyacridine is the starting point for the

synthesis

of

both

acridine-l, 4-diones

corresponding 1,2-quinones (J. Renault

and

et al.,


the

Eur. J.

Med. Chem.-Chim. Ther., 1981, 16, 24).

0

0

R

A

MeOH
NHAr

MeO
X

HCI

0

0

MeOH//
HC1/ / ArNH2
0
A


r

N

R
H

~

X

(3)

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Cyclisation of 4-chloro-N-(3-nitrophenyl)anthranilic

acid

(4) by means of phosphorus oxychloride gives a mixture of
1- and 3-nitro-6,9-dichloroacridine.

The 1-isomer reacts

selectively with pyridine to give the 9-pyridinium salt
and

hence


separation

(B. Wysocka-Skrzela,
Chem.,

1977, 51,

of

the

isomers

is

possible

K. Biskup and A. Ledochowski, Rocz.

2411).

The 9-chlorine

atom

in each

isomer is exclusively displaced by phenol~ the resulting
9-phenoxy


substituent

is

also

labile.

reaction with mono-Boc-protected
di-

and

tri-

9-acridyl

amines

derivatives

polyamines to be prepared

(5,

For

example.


enables
6

and

mono-,
7)

of

(J.B. Hansen and O. Buchardt,

Chem. Comm., 1983, 162) and several 9-acridylamino acids
have

been

obtained

Wysocka-Skrzela,

from

l-nitro-9-phenoxyacridine

G. Weltrowska

and A. Ledochowski,

(B.

Pol.

J. Chem., 1980, 5__44,619).

NH(CII2)nNH2
C l ~

COOH

NO

2

(4)

(5)

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~

N

NH
I

(~H2)n
NH
HN/~/


(6)

(7)

2,9-Dimethylacridine
methyldiphenyl~aine

results

from

the

reaction

of

4-

with acetic acid in the presence of

zinc chloride; the route involves decarbo~lation

of N-p-

tolylanthranilic acid, itself a precursor of the acridine
ring system (J.R. Patton and K.H. Dudley. J. heterocyclic
C~em.,


1979,

16, 257).

It is ~ s o

of interest to note

that C-9 of acridine can be introduced
vapour

phase

(R.E. Busby

reaction

of

c~oroform

directly by the

and

diphenylmnine

et al., J. ch~,. Research (M), 1980, 4935).

co::


CuCO
225~

NH

Me

CH3C~H, ZnC12

220~

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Flash

vacuum

affords

a

pyrolysis

mixture

derivative,

of


of

2-azidodiphenylmethane

acridine

and

its

(8)

9,10-dihydro

the composition of the product varying with

the reaction temperature

(M.G. Hicks and G. Jones, Chem.

Comm., 1983, 1277).

Temp

% composition

(~

acridine


9, lO-dihydro

350

10

90

500

33

66

700

95

5

(8)

Both a dihydroacridine

and an acridine

thermolysis of 2-azidotriphenylmethanes

result


from the

(9) (R.N. Carde

et al., J. chem. Soc. Perkin I, 1978, 1211; 1981, 1132).
In

an

(I0),

analogous
generated

tosylhydrazone

manner,
in

2,(phenylamino)phenylcarbenes

the

sodium

vapour

salts,


phase
insert

from
into

the
the

adjacent ortho-position although giving only the dihydro
derivative

(W. D. Crow and H. McNab, Austral.

J. Chem.,

1981, 34, 1037).
...=..

H

p-MeOC 6 H4

CH
R

(9)

"NH


(i0)

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Me


(II)

The quinone methide
Diels-Alder

reaction

when heated with
include

the

(13) both
pyrolysis

derived from flavan by a retro-

gives only

aniline.

However,


diphenylmethane

of which

a 4% yield of acridine

yield

(12) and
the

(J.L. Asherson,

the other products
the Mannich base

tricyclic

compound

upon

O. Bilgic and D.W. Young,

J.

chem. Soc. Perkin I, 1980, 522).

A " I~


~ph

CH20

'

PhNH2

(11)
+
OH

OH NH2
(12)

Both

(13)

2- N -phenyl aminobenzyl

alcohol

and

l-

phenylbenzoxazine (14) break down to the azaxylylene (15)
at


high

silica

or

alumina the reaction temperature is reduced from 650~

to

400~

temperatures;

in

Electrocyclisation

dihydroacridine

with

some

the

of

presence


the

acridine,

of

azaxylylene
the

gives

extent

dehydrogenation increasing at temperatures over 650~

of
(I.

Hodgetts, S.J. Noyce and R.C. Storr, Tetrahedron Letters,
1984, 5435).

(14)

(15)

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Alkylation of acridine at C-9 occurs on reaction with


~-

alkoxyalkyl lithium compounds and subsequent oxidation of
the

resul ring

9,10-dihydroacridine

Various

functional

leading

notably

group
to

derivative

interconversions
acridines

are

bearing

(16).


possible

phosphorus

containing substituents at the 9-position (L. Hornet and
W. Hallenbach, Phosphorus and Sulphur, 1984, 20, 173).
(CH2 )nOR

O
.~,

FeCl 3
H

(16)

Cyclisation

of

2-carboxytriphenylamines

by

phosphorus

oxychloride

provides access to 9-amino-10-arylacridinium


salts

the

v~G

9-chloro

D.H. Birtwistle

and P.B.

derivatives
Wyatt,

J.

chem.

(R. M.

Acheson,

Research

(M),

1986, 2762).


An alternative approach to 9-substituted acridinium salts
and

thence

conversion

the

corresponding

of

acridines

9-acridones

involves

into

the

the
9-

trifluoromerhanesulphonyloxy

acridinium salts (17), which


react readily with halides,

pseudohalides

and isothiocyanate,

and sulphur nucleophiles

and G. Maas, Z. Naturforsch.,
base

results

on

9,9'-Bisacridine

such as azide

reaction
ethers

1984, 39b, 1399).
with

are

(B. Singer
The free


diisopropylethylamine.

also

methodology.

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available

by

this