New one-pot reaction of perimidines with nitroethane and acylating agents in polyphosphoric acid

Full text of DOI:10.1007/s11172-014-0648-x

Russian Chemical Bulletin, International Edition, Vol. 63, No. 7, pp. 1643—1645, July, 2014
1643
Letters to the Editor
New oneꢀpot reaction of perimidines with nitroethane
and acylating agents in polyphosphoric acid*
A. V. Aksenov, N. A. Aksenov, A. N. Smirnov, V. I. Goncharov, S. N. Ovcharov, and I. V. Aksenova
North Caucasus Federal University,
1a ul. Pushkina, 355009 Stavropol´, Russian Federation.
Fax: +7 (865 2) 35 4033. Eꢀmail: alexaks05@rambler.ru
A structural framework of [c,d]ꢀannulated indoles is
encountered with in nature and synthetic compounds, exꢀ
hibiting various biological activity.1—3 Low toxic polyꢀ
heterocyclic analogs of acenaphthenes and benzopyrenes
can in prospects replace these widely used photochemical
probes,4 making them more attractive for medical appliꢀ
cation. Besides, such structures can be used in nanoꢀ
technology for modeling reactivity of azafullerenes5 and
atomꢀmodified nanotubes.6
Earlier, we have described a number of methods for
periꢀannulation of pyrrole ring.7—12 These methods have
some disadvantages: some of them require preliminary
functionalization of perimidine,11,12 other use sodium
azide, which in acidic medium can form highly toxic and
explosive hydrazoic acid.7—10 In the present work, we suggest
two approaches to the synthesis of such compounds, which
do not have the disadvantages mentioned above. These
approaches are based on the reaction recently discovered
in our laboratory,13—15 electrophilic acetamidation of
arenes with nitroethane in polyphosphoric acid (PPA)**
We showed that the reaction of 1 mmol of perimidines
1a—c and 2 mmol of nitroethane (Scheme 1) in 2—3 g
PPA at 100—105 C for 5 h (monitoring by thinꢀlayer
chromatography) with subsequent addition of 1.5 mmol
of the corresponding 1,3,5ꢀtriazine 3 and heating for
another 3 h at 110—120 C (3b,c) or 90—100 C (3a) leads
to 1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalenes 5a—i in
36—51% yield.
It is probable that the reaction proceeds through the
acetamidation of perimidines 1a—c with the formation of
acetamides 2a—c (see Ref. 15), which through the reacꢀ
tion with 1,3,5ꢀtriazines, successive ring opening and hetꢀ
erocyclization are converted to the intermediate Nꢀacetyl
derivatives 4a—i. Similar processes involving 1,3,5ꢀtriꢀ
azines in PPA are considered in details in the review.17
Compounds 4a—i undergo hydrolysis after treatment of
the reaction mixture with water to give indoles 5a—i.
We showed that more available carboxylic acids can be
used instead of 1,3,5ꢀtriazines for the preparation of comꢀ
pounds 5d—i by this reaction (Scheme 2), with the yields
remaining on the same level.
The mechanism is similar to that described above.
In conclusion, we have developed two method for
the synthesis of 1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenꢀ
alenes 5a—i based on the reaction of perimidines
* Dedicated to Academician of the Russian Academy of Sciences
O. N. Chupakhin on the occasion of his 80th birthday.
** Polyphosphoric acid containing 86% of P2O5 was obtained
according to the known procedure (see Ref. 16).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1643—1645, July, 2014.
1066ꢀ5285/14/6307ꢀ1643 © 2014 Springer Science+Business Media, Inc.

1644
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 7, July, 2014
Aksenov et al.
Scheme 1
1—3: R1 = R2 = H (a), Me (b), Ph (c)
Starting
compounds
1a, 3a
1b, 3a
1c, 3a
Product
R1
R2
Starting
compounds
1a, 3b
1b, 3b
1c, 3b
Product
R1
R2
Starting
compounds
1a, 3c
1b, 3c
1c, 3c
Product
R1
R2
4a, 5a
4b, 5b
4c, 5c
H
Me
Ph
H
H
H
4d, 5d
4e, 5e
4f, 5f
H
Me
Ph
Me
Me
Me
4g, 5g
4h, 5h
4i, 5i
H
Me
Ph
Ph
Ph
Ph
Scheme 2
with nitroethane and 1,3,5ꢀtriazines or carboxylic acids
in PPA.
1H NMR spectra were recorded on a Bruker Avance III
spectrometer (400 MHz), using SiMe4 as an internal standard.
Reaction progress and individuality of synthesized compounds
were monitored by chromatography on Silufol UVꢀ254 plates,
using a 1 : 1 ethyl acetate—ethanol solvent system. Nitroethane,
1,3,5ꢀtriazine, 2,4,6ꢀtriphenylꢀ1,3,5ꢀtriazine, acetic and benzoic
acids are commercial agents (Aldrich). Perimidine,18 2ꢀmethylꢀ
and 2ꢀphenylperimidine,18 and 2,4,6ꢀtrimethylꢀ1,3,5ꢀtriazine19
were obtained according to the described procedures.
Synthesis of triazacyclopentaphenalenes 5a—i (general proꢀ
cedure). A mixture of the corresponding perimidine 1a—c
(1 mmol) and nitroethane (0.15 g, 2 mmol) in PPA (2—3 g) was
heated at 100—105 C for 3 h (TLC monitoring). Then, the
corresponding 1,3,5ꢀtriazine or carboxylic acid (1.5 mmol) was
added and the mixture was allowed to stand for 5 h at 110—120 C
(3b,c) or 90—100 C (3a). The reaction mixture was cooled to
80 C, poured into cold water (30 mL) with stirring, aqueous
ammonia was used to bring the pH to ~8, a precipitate formed
was filtered off, the mother liquor was extracted with benzene
(3×50 mL), a precipitate was dried and extracted in a Soxhlet
extractor with benzene (100 mL) for 3 h. The benzene fractions
were combined, the solvent was evaporated. Compounds obꢀ
tained were purified by recrystallization.
i.1) EtNO2/PPA; 2) R2COOH; 3) H2O.
Ref. 7: m.p. 207—209 C. NMR spectrum agrees with that deꢀ
scribed in the work.7
6ꢀMethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (5b).
The yield was 0.106 g (51%), m.p. 237—238 C (benzene). The
data in Ref. 7: m.p. 237—238 C. NMR spectrum agrees with
that described in the work.7
6ꢀPhenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (5c). The
yield was 0.105 g (39%), m.p. 201—203 C (benzene). The data
in Ref. 7: m.p. 201—203 C. NMR spectrum agrees with that
described in the work.7
1Hꢀ1,5,7ꢀTriazacyclopenta[c,d]phenalene (5a). The yield
was 0.081 g (42%), m.p. 207—209 C (benzene). The data in
2ꢀMethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (5d).
The yield was 0.079 g (38%) (from 2,4,6ꢀtrimethylꢀ1,3,5ꢀtriꢀ

New one pot reaction of perimidines
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 7, July, 2014
1645
azine), 0.085 g (41%) (from acetic acid), m.p. 259—260 C (from
benzene). The data in Ref. 7: m.p. 259—260 C. NMR spectrum
agrees with that described in the work.7
3. M. D. Varney, C. L. Palmer, J. G. Deal, S. Webber, K. M.
Welsh, C. A. Bartlett, C. A. Morse, W. W. Smith, C. A.
Janson, J. Med. Chem., 1995, 38, 1892.
2,6ꢀDimethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (5e).
The yield was 0.104 g (47%) (from 2,4,6ꢀtrimethylꢀ1,3,5ꢀtriꢀ
azine), 0.106 g (48%) (from acetic acid), m.p. 271—272 C (from
benzene). The data in Ref. 7: m.p. 271—272 C. NMR spectrum
agrees with that described in the work.7
2ꢀMethylꢀ6ꢀphenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenꢀ
alene (5f). The yield was 0.13 g (46%) (from 2,4,6ꢀtrimethylꢀ
1,3,5ꢀtriazine), 0.139 g (49%) (from acetic acid), m.p. 245—246 C
(from benzene with light petroleum). The data in Ref. 7:
m.p. 245—246 C. NMR spectrum agrees with that described in
the work.7
2ꢀPhenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (5g).
The yield was 0.097 g (36%) (from 2,4,6ꢀtriphenylꢀ1,3,5ꢀtriꢀ
azine), 0.121 g (41%) (from benzoic acid), m.p. 263—265 C
(from benzene). The data in Ref. 7: m.p. 263—265 C. NMR
spectrum agrees with that described in the work.7
2ꢀPhenylꢀ6ꢀmethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenꢀ
alene (5h). The yield was 0.13 g (46%) (from 2,4,6ꢀtriphenꢀ
ylꢀ1,3,5ꢀtriazine), 0.136 g (48%) (from benzoic acid), m.p.
291—292 C (from benzene). The data in Ref. 7: m.p. 291—292 C.
NMR spectrum agrees with that described in the work.7
2,6ꢀDiphenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (5i).
The yield was 0.148 g (43%) (from 2,4,6ꢀtriphenylꢀ1,3,5ꢀtriꢀ
azine), 0.159 g (46%) (from benzoic acid), m.p. 169—171 C
(from benzene with light petroleum). The data in Ref. 7:
m.p. 169—171 C. NMR spectrum agrees with that described in
the work.7
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This work was financially supported by the Russian
Foundation for Basic Research (Project No. 13ꢀ03ꢀ
00304a).
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2009, 167].
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Received June 9, 2014