New one pot synthesis of 1H-1,5,7-triazacyclopenta[c,d]phenalenes

Full text of DOI:10.1007/s11172-013-0117-y

Russian Chemical Bulletin, International Edition, Vol. 62, No. 3, pp. 855—856, March, 2013
855
Letters to the Editor
New one pot synthesis of 1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalenes*
A. S. Lyakhovnenko, N. A. Aksenov, A. S. Kolesnikova, I. V. Aksenova, and A. V. Aksenov
North Caucasus Federal University,
1a ul. Pushkina, 355009 Stavropol´, Russian Federation.
Fax: +7 (865 2) 35 4033. Eꢀmail: kꢀbiochemꢀorg@stavsu.ru
1Hꢀ1,5,7ꢀTriazacyclopenta[c,d]phenalenes (1a—g) are
of interest from the point of view of the search for biologiꢀ
cally active compounds, since they are the structural anaꢀ
logs of known antitumor agents, for example, AG 331 (see
Ref. 1). Earlier, we have developed a number of methods
for the synthesis of these compounds.2—5 These methods
have the disadvantage of using polyphosphoric acid (PPA)
as a solvent, and, as a consequence, difficulties in handꢀ
ling scaled amounts of reagents. In the present work, we
suggest a one pot method for the synthesis of compounds
1a—g, which has no such a disadvantage. It is based on
the following sequence: the azoꢀcoupling of carbonyl comꢀ
pounds 2a—g, the reduction of the intermediate azo comꢀ
pounds 3a—g, and the heterocyclization of the interꢀ
mediate amines 4a—g (Scheme 1).
The total yields were 34—47%.
Scheme 1
R = Me, R´ = H (a); R = H, R´ = Me (b); R = R´ = Me (c); R = Ph, R´ = Me (d); R = H, R´ = Ph (e); R = Me, R´ = Ph (f);
R = R´ = Ph (g); Ar = 4ꢀO3SC6H4
* Dedicated to Academician of the Russian Academy of Sciences I. P. Beletskaya on the occasion of her anniversary.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 0854—0856, March, 2013.
1066ꢀ5285/13/6203ꢀ855 © 2013 Springer Science+Business Media, Inc.

856
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 3, March, 2013
Lyakhovnenko et al.
Synthesis of 1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalenes (genꢀ
6ꢀMethylꢀ2ꢀphenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenꢀ
alene (1f). The yield was 0.116 g (41%). M.p. 291—292 C (from
benzene; Ref. 4: m.p. 291—292 C). 1H NMR spectrum is simiꢀ
lar to that given in the work.4
2,6ꢀDiphenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (1g).
The yield was 0.135 g (39%). M.p. 169—171 C (from benzene
with light petroleum; Ref. 4: m.p. 169—171 C). 1H NMR specꢀ
trum is similar to that given in the work.4
eral procedure). A mixture of the corresponding 6(7)ꢀformylꢀ
(acyl)perimidine (2a—g) (1 mmol), diazobenzenesulfonic acid
(0.276 g, 1.5 mmol), and sodium acetate (0.164 g, 2 mmol) in
acetic acid (10 mL) was vigorously stirred at room temperature
for 1 h, then heated to 50 C over 15 min, followed by the
addition of zinc dust (0.32 g, 5 mmol) and reflux for 1 h with
stirring. The reaction mixture was cooled to 80 C, poured into
a stirred cold water (30 mL), pH was raised to ~8. A precipitate
formed was filtered off, the mother liquor was extracted with
benzene (3×50 mL), the precipitate was dried and extracted in
a Soxhlet extractor with benzene (100 mL) over 3 h. The benzꢀ
ene phases were combined, the solvent was evaporated. The
compounds obtained were purified by recrystallization.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00193a).
References
NMR spectra were recorded on a Bruker WPꢀ200 (200 MHz)
spectrometer, using SiMe4 as an internal standard. The reaction
progress and individuality of the compounds synthesized were
monitored by TLC on Silufol UVꢀ254 plates, using the 1 : 1 ethyl
acetate—ethanol solvent system as the eluent. Diazobenzeneꢀ
sulfonic acid was obtained by the known method.6 6(7)ꢀFormylꢀ
(acyl)perimidines were obtained according to the procedures
described earlier.7,8
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6ꢀMethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (1a).
The yield was 0.07 g (34%). M.p. 237—238 C (from benzene;
1
Ref. 4: m.p. 237—238 C). H NMR spectrum is similar to that
given in the work.4
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2ꢀMethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (1b).
The yield was 0.083 g (40%). M.p. 259—260 C (from benzene;
1
Ref. 2: m.p. 259—260 C). H NMR spectrum is similar to that
given in the work.2
2,6ꢀDimethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (1c).
The yield was 0.102 g (46%). M.p. 271—272 °C (from benzene;
1
Ref. 2: m.p. 271—272 C). H NMR spectrum is similar to that
given in the work.2
2ꢀMethylꢀ6ꢀphenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenꢀ
alene (1d). The yield was 0.133 g (47%). M.p. 245—246 C (from
benzene with light petroleum; Ref. 4: m.p. 245—246 C).
1H NMR spectrum is similar to that given in the work.4
2ꢀPhenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (1e). The
yield was 0.121 g (45%). M.p. 263—265 C (from benzene; Ref. 4:
m.p. 263—265 C). 1H NMR spectrum is similar to that given in
the work.4
Received November 8, 2012;
in revised form February 20, 2013