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

Full text of DOI:10.1007/s10593-011-0709-0

Chemistry of Heterocyclic Compounds, Vol. 46, No. 12, March, 2011 (Russian Original Vol. 46, No. 12, December, 2010)
NOVEL ONE-POT SYNTHESIS OF
1H-1,5,7-TRIAZACYCLOPENTA[c,d]PHENALENES
A. V. Aksenov1*, A. S. Lyakhovnenko1, T. S. Perlova1, and I. V. Aksenova1
Keywords: perimidines, 1H-1,5,7-triazacyclopenta[c,d]phenalenes, peri-annelation, reduction, nitration.
1H-1,5,7-Triazacyclpenta[c,d]phenalenes 4a-g are of interest with respect to the search for biologically
active compounds since they are structural analogs of known antitumor agents, e.g. AG 331 [1]. We have
previously developed a series of methods for the synthesis of these compounds [2-4]. The drawback of these
methods is the use of polyphosphoric acid (PPA) as solvent and hence the difficulty of working on a large scale.
In this work we propose the removal of the drawback to this synthetic method based on a one pot reaction
sequence for compounds 4a-g, viz. nitration of the carbonyl compounds 1a-g, reduction of the intermediate nitro
compounds 2a-g, and heterocyclization of the amines 3a-g. The overall yields are 64-87%.
R
R
R
R
N
N
N
NH
N
NH
N
NH
HCl
Zn
HNO3
AcOH
AcOH
AcOH
N
H
R1
NH2
R1
NO2
R1
R1
O
O
O
4a–g
3a–g
1a–g
2a–g
1H NMR spectra were recorded on a Bruker WP-200 instrument (200 MHz) with TMS as internal
standard. Monitoring of the reaction course and purity of the synthesized compounds was carried out on Silufol
UV-254 plates in the system ethyl acetate–alcohol (1:1).
Synthesis of Compounds 4a-g (General Method). A mixture of ketone 1a-g (1 mmol), carbamide
(0.03 g, 0.5 mmol), and nitric acid (d =1.4, 0.105 g, 1.05 mmol) in acetic acid (10 ml) was refluxed for 3 min. It
was then treated with zinc powder (0.32 g, 5 mmol), refluxed for 1 h, conc. HCl (1 ml) was added, and then
refluxed for a further 4 h (TLC monitoring). The reaction mixture was filtered and treated with water (50 ml).
The precipitate formed was filtered off, the mother liquor was extracted with hot benzene (650 ml), and washed
with a 10% solution of sodium carbonate (230 ml). Solvent was evaporated off and the residue was combined
with the precipitate. The compound obtained was purified by crystallization.
_______
* To whom correspondence should be addressed, e-mail: k-biochem-org@stavsu.ru, alexaks05@rambler.ru.
1Stavropol State University, Stavropol 355009, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1906-1908. December, 2010.
Original article submitted November 24, 2010.
0009-3122/11/4612-1545©2011 Springer Science+Business Media, Inc.
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6-Methyl-1H-1,5,7-triazacyclopenta[c,d]phenalene (4a). Yield 0.132 g (64%); mp 237-238ºC
(benzene) (mp 237-238ºC [3]). The 1H NMR spectrum was similar to that reported in [3].
2-Methyl-1H-1,5,7-triazacyclopenta[c,d]phenalene (4b). Yield 0.131 g (73%); mp 259-260ºC
(benzene) (mp 259-260ºC [2]). The 1H NMR spectrum was similar to that reported in [2].
2,6-Dimethyl-1H-1,5,7-triazacyclopenta[c,d]phenalene (4c). Yield 0.179 g (81%); mp 271-272ºC
(benzene) (mp 271-272ºC [2]). The 1H NMR spectrum was similar to that reported in [2].
2-Methyl-6-phenyl-1H-1,5,7-triazacyclopenta[c,d]phenalene (4d). Yield 0.240 g (85%); mp 245-246ºC
(benzene with petroleum ether) (mp 245-246ºC [3]). The 1H NMR spectrum was similar to that reported in [3].
2-Phenyl-1H-1,5,7-triazacyclopenta[c,d]phenalene (4e). Yield 0.223 g (83%); mp 263-265ºC
(benzene) (mp 263-265ºC [3]). The 1H NMR spectrum was similar to that reported in [3].
6-Methyl-2-phenyl-1H-1,5,7-triazacyclopenta[c,d]phenalene (4f). Yield 0.243 g (86%); mp 291-292ºC
(benzene) (mp 291-292ºC [3]). The 1H NMR spectrum was similar to that reported in [3].
2,6-Diphenyl-1H-1,5,7-triazacyclopenta[c,d]phenalene (4g). Yield 0.300 g, (87%); mp 169-171ºC
(benzene with petroleum ether) (mp 169-171ºC [3]). The 1H NMR spectrum was similar to that reported in [3].
This work was carried out with the support of the Russian Fund for Basic Research (grant 10-03-
00193a).
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