Synthesis of 1H-1,5,7-triazacyclopenta[c,d]phenalenes involving electrophilic amination of 1H-perimidines with sodium azide in polyphosphoric acid

Full text of DOI:10.1007/s11172-011-0122-y

Russian Chemical Bulletin, International Edition, Vol. 60, No. 4, pp. 771—772, April, 2011
771
Synthesis of 1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalenes
involving electrophilic amination of 1Hꢀperimidines with sodium azide
in polyphosphoric acid
A. V. Aksenov, A. S. Lyakhovnenko, and A. V. Andrienko
Stavropol State University, Department of Biology and Chemistry,
1a ul. Pushkina, 355009 Stavropol, Russian Federation.
Fax: +7 (865 2) 35 4033. Eꢀmail: kꢀbiochemꢀorg@stavsu.ru
Earlier, we have developed several methods of periꢀ
ing into account high biological activity of many indole
annulation of 6ꢀmembered rings to perimidines.1—4 Takꢀ
derivatives, in the present work we proposed a method
of periꢀannulation of the pyrrole ring to perimidines,
which is based on the recently found reagent combination
NaN3/polyphosphoric acid (PPA*).6 We showed that the
reaction of perimidines 1a—c with a threefold molar excess
of NaN3 in PPA at 80—90 °C for 4 h followed by addition
of a carboxylic acid and heating for 5 h at 110—120 °C
results in the earlier unknown 1Hꢀ1,5,7ꢀtriazacycloꢀ
penta[c,d]phenalenes 2a—e in yields of 48—67% (Scheme 1).
The proposed mechanism of this transformation inꢀ
cludes the formation of triazenes 3 according to the mechꢀ
anism given in Ref. 6, their acylation and cyclization folꢀ
lowed by the successive formation of intermediates 4, 5,
and 6, which results in 1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]ꢀ
phenalenes 2a—e (Scheme 2).
Scheme 1
i. 1) NaN3/PPA; 2) R´CO2H
R
H
Me
Ph
H
R´
—
—
—
Me
R
R´
Me
Me
Ph
Ph
1a
1b
1c
2a
2b
2c
2d
2e
Me
Ph
Me
Ph
Thus, the consecutive reaction of sodium azide and
carboxylic acids with 1Нꢀperimidines in PPA affords the
hitherto unknown 1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenꢀ
Scheme 2
i. NaN3, PPA; ii. R´CO2H, PPA.
* PPA containing 86% of P2O5, which has been prepared according to the previously described procedure,5 was used.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 755—756, April, 2011.
1066ꢀ5285/11/6004ꢀ771 © 2011 Springer Science+Business Media, Inc.

772
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 4, April, 2011
Aksenov et al.
6ꢀMethylꢀ2ꢀphenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenꢀ
alene (2d) was obtained in a yield of 0.15 g (53%), m.p. 291—292 °C
(from benzene). 1H NMR, δ: 2.92 (s, 3 H, Me); 7.49 (t, 1 H, Ph,
Н(4), J = 7.7 Hz); 7.49 (t, 2 H, Ph, Н(3), H(5), J = 7.7 Hz); 7.68
(d, 1 H, H(9), J = 9.0 Hz); 7.81 (d, 1 H, H(3), J = 9.0 Hz); 8.19
(d, 2 H, Ph, H(2), H(6), J = 7.7 Hz); 8.34 (d, 1 H, H(4), J = 9.0 Hz);
8.73 (d, 1 H, H(8), J = 9.0 Hz); 12.9 (br.s, 1 H, NH). Found (%):
C, 80.69; H, 4.55; N, 14.76. C19H13N3. Calculated (%): C, 80.55;
H, 4.62; N, 14.83.
2,6ꢀDiphenylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (2e)
was obtained in a yield of 0.166 g (48%), m.p. 169—170 °C (from
benzene with hexane). 1H NMR, δ: 7.5—7.7 (m, 6 H, 2ꢀPh,
6ꢀPh, Н(3), H(4), H(5)); 7.85 (d, 1 H, H(9), J = 9.0 Hz); 7.98
(d, 1 H, H(3), J = 9.0 Hz); 8.21 (d, 2 H, 2ꢀPh, H(2), H(6),
J = 7.7 Hz); 8.41 (d, 1 H, H(4), J = 9.0 Hz); 8.73 (d, 2 H, 6ꢀPh,
H(2), H(6), J = 8.1 Hz); 8.81 (d, 1 H, H(8), J = 9.0 Hz); 13.0
(br.s, 1 H, NH). Found (%): C, 83.62; H, 4.29; N, 12.09.
C24H15N3. Calculated (%): C, 83.46; H, 4.38; N, 12.17.
alenes through the oneꢀpot reaction. In future, we intend
to study to what extent this reaction is general with respect
to other azaphenalenes.
NMR spectra were recorded on a Bruker WPꢀ200 (200 MHz)
instrument in DMSOꢀd6 using SiMe4 as the internal standard.
The course of the reaction and the purity of the compounds
synthesized were monitored by TLC on Silufol UVꢀ254 plates
using chloroform as a solvent. Perimidine, 2ꢀmethylꢀ, and
2ꢀphenylperimidine 1a—c were prepared according to known
procedures.7
Synthesis of compounds 2a—e (general procedure). A mixture
of the corresponding 1Нꢀperimidine 1a—c (1 mmol) and NaN3
(0.195 g, 3 mmol) in PPA (2—3 g) were thoroughly stirred at
80—90 °C for 4 h (TLC control). Then, a carboxylic acid
(4 mmol) was added, the temperature was raised to 110—120 °C,
and the mixture was stirred for additional 5 h. The reaction
mixture was cooled to 80 °C, poured into cold water (30 mL),
and alkalified with aqueous ammonia to pH ~8. The precipitate
that formed was filtered off, the mother liquor was extracted
with benzene (3×50 mL), and the precipitate was dried and exꢀ
tracted in a Soxhlet apparatus with benzene (100 mL) for 3 h.
The benzene extracts were combined and the solvent was reꢀ
moved. The compounds were purified by recrystallization.
2ꢀMethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (2a) was
obtained in a yield of 0.128 g (62%), m.p. 259—260 °C (from
benzene). 1H NMR, δ: 2.98 (s, 3 H, Me); 7.58 (d, 1 H, H(9),
J = 9.0 Hz); 7.78 (d, 1 H, H(3), J = 9.0 Hz); 8.31 (d, 1 H, H(4),
J = 9.0 Hz); 8.47 (d, 1 H, H(8), J = 9.0 Hz); 9.36 (s, 1 H, H(6));
13.1 (br.s, 1 H, NH). Found (%): C, 75.54; H, 4.31; N, 20.15.
C13H9N3. Calculated (%): C, 75.35; H, 4.38; N, 20.28.
2,6ꢀDimethylꢀ1Hꢀ1,5,7ꢀtriazacyclopenta[c,d]phenalene (2b)
was obtained in a yield of 0.148 g (67%), m.p. 271—272 °C (from
benzene). 1H NMR, δ: 2.87 (s, 3 H, Me(2)); 2.95 (s, 3 H, Me(6));
7.50 (d, 1 H, H(9), J = 9.0 Hz); 7.67 (d, 1 H, H(3), J = 9.0 Hz);
8.24 (d, 1 H, H(4), J = 9.0 Hz); 8.41 (d, 1 H, H(8), J = 9.0 Hz);
12.8 (br.s, 1 H, NH). Found (%): C, 76.18; H, 4.95; N, 18.87.
C14H11N3. Calculated (%): C, 76.00; H, 5.01; N, 18.99.
2ꢀMethylꢀ6ꢀphenylꢀ1Hꢀ1,5,7ꢀtriazacylcopenta[c,d]phenꢀ
alene (2c) was obtained in a yield of 0.184 g (65%), m.p.
245—246 °C (from benzene with hexane). 1H NMR, δ: 2.98
(s, 3 H, Me); 7.53 (m, 3 H, Ph, Н(3), H(4), H(5)); 7.66 (d, 1 H,
H(9), J = 9.1 Hz); 7.85 (d, 1 H, H(3), J = 8.8 Hz); 8.32 (d, 1 H,
H(4), J = 8.8 Hz); 8.50 (d, 1 H, H(8), J = 9.1 Hz); 8.70 (d, 2 H,
Ph, H(2), H(6), J = 7.3 Hz); 13.1 (br.s, 1 H, NH). Found (%):
C, 80.66; H, 4.56; N, 14.78. C19H13N3. Calculated (%): C, 80.55;
H, 4.62; N, 14.83.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ00193a).
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Received May 28, 2010