Russian Chemical Bulletin, International Edition, Vol. 50, No. 9, pp. 16631667, September, 2001 1663
1066-5285/01/5009-1663 $25.00 ©2001 Plenum Publishing Corporation
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 15851589, September, 2001.
Transformations of 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones
in the presence of amines
I. I. Barabanov, L. G. Fedenok, N. E. Polyakov, and M. S. Shvartsberg
«
Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences,
3 ul. Institutskaya, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 2350. E-mail: shvarts@kinetics.nsc.ru
When heated in piperidine, 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones un-
dergo cyclization into 2-(1-hydroxyalkyl)naphtho[2,3-g]indole-6,11-diones. In contrast,
1-amino-2-(3-hydroxy-3-phenylpropynyl)-9,10-anthraquinone reacts with primary and sec-
ondary amines to give the corresponding 1-amino-2-(1-amino-2-benzoylvinyl)-9,10-an-
thraquinones, which undergo cyclization into 4-dialkylamino- or 4-alkylamino-2-phenyl-
naphtho[2,3-h]quinoline-7,12-diones. Heating of the starting phenylpropynol with Et
3
N
causes its dehydrogenation and isomerization.
Key words: 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-anthraquinones, addition of amines,
dehydrogenation, isomerization, cyclization, 2-(1-hydroxyalkyl)naphtho[2,3-g]indole-6,11-
diones, 4-dialkylamino-2-phenylnaphtho[2,3-h]quinoline-7,12-diones.
Fused quinoid heterocycles are interesting as sub-
stances with potential biological activity.
13
A general
approach to their synthesis is based on the use of
alkynyl derivatives of simple quinones (anthra-, naphtho-,
and benzoquinones) as key intermediates.
48
Ear-
lier,
5,911
it was shown that the addition of amines to
alkynylquinones containing a functional group vicinal
to the alkynyl substituent changes the geometry of the
unsaturated fragment and, in most cases, allows easy
cyclization of the adducts obtained. Depending on the
structure and/or the reaction conditions, the resulting
heterocycle can either lose or retain the amino group.
We have developed methods for the synthesis of
naphthoquinoline- and naphthoindolediones from amino
adducts of different vicinal oxo-, alkoxycarbonyl-,
alkyl-, and arylacetylenic derivatives of aminoanthra-
quinones.
5,1214
In the present work, the possibility and specific
features of the formation of adducts and the hetero-
cyclization of 1-amino-2-(3-hydroxyalk-1-ynyl)-9,10-
anthraquinones (13) in their reactions with amines
were studied.
Results and Discussion
It was found that, when heated in piperidine at
80106 °C, 1-amino-2-(3-hydroxyprop-1-ynyl)- (1) and
1-amino-2-(3-hydroxyhex-1-ynyl)-9,10-anthraquinones
(2) undergo intramolecular cyclization into 2-(1-hydroxy-
alkyl)naphtho[2,3-g]indole-6,11-diones (4, 5) in 58 and
77% yields, respectively (Scheme 1).
Closure of the pyrrole ring in the heterocyclization
of alcohols 1 and 2 under these conditions is hardly
possible without prior addition of the amine to the triple
bond. At the same time, no intermediates were detected
chromatographically during the cyclization. This sug-
gests that the multistep reaction includes the addition of
the amine to compounds 1 and 2, cyclization proper of
the adduct, and elimination of the amine, the formation
of the adduct being the rate-limiting step.
Unlike alcohols 1 and 2, phenyl analog 3 reacts with
piperidine, as well as with diethylamine and butylamine,
at 4080 °C in dioxane or without a solvent to give
aminovinyl ketones 6ac rather than expected substi-
tuted aminoallyl alcohols.
Such an unusual outcome of the reaction of com-
pound 3 with amines prompted us to search for addi-
tional confirmation of the structures of adducts 6ac.
The cyclization of amino ketones 6ac in the presence
of small amounts of H
2
SO
4
in benzene at 20 °C gave
dialkyl(or alkyl)amino-2-phenylnaphtho[2,3-h]quinoline-
7,12-diones (7ac). In addition, heating of alcohol 3 in
morpholine at 120 °C for 1 h yielded naphthoquinoline-
dione 7d. Adducts 6ac and cyclization products 7ac
and 7d were compared with authentic compounds syn-
thesized
13
from 1-amino-2-benzoylethynyl-9,10-an-
thraquinone (8). The substances obtained by two inde-
pendent methods were identical, which unambiguously
proves the correctness of structures 6ac for the ad-
ducts of amines to alcohol 3.
While studying the way in which alcohol 3 is trans-
formed into amino ketones 6, we found that heating of
3 in Et
3
N (8 h, 80 °C) unlike secondary and primary
amines, it cannot add to the triple bondaffords two
products, namely, 1-amino-2-benzoylethynyl- (8) and
E-1-amino-2-(2-benzoylvinyl)-9,10-anthraquinones (9)
in virtually quantitative yield in the ratio 1 : 1 (Scheme 2).