Synthesis of N-phenyl-1,5,7-triazacyclopenta[cd]- phenalenes by the reaction of 1H-perimidine carbonyl derivatives with nitrobenzene

Full text of DOI:10.1007/s10593-014-1531-2

Chemistry of Heterocyclic Compounds, Vol. 50, No. 5, July, 2014 (Russian Original Vol. 50, No. 5, May, 2014)
LETTERS TO THE EDITOR
SYNTHESIS OF N-PHENYL-1,5,7-TRIAZACYCLOPENTA[cd]-
PHENALENES BY THE REACTION OF 1H-PERIMIDINE
CARBONYL DERIVATIVES WITH NITROBENZENE
S. V. Shcherbakov1, D. A. Lobach1, M. Rubin2, and A. V. Aksenov1*
Keywords: indoles, nitrobenzene, 1H-perimidines, 1H-1,5,7-triazacyclopenta[cd]phenalenes, peri
annelation.
A [cd]-annelated indole structural framework is often met in natural and synthetic compounds which
show a variety of biological activity [1-3]. In addition, as low toxicity analogs of acenapthenes and
benzopyrenes, such polyheterocyclic molecules may in the future replace these widely used photochemical
probes [4] and this makes them more attractive for medical applications. Similar structures can be used in
nanotechnology for modeling the reactivity of azafullerenes [5] and atom-modified nanotubes [6].
We have previously reported development of a method for the direct peri annelation of a pyrrole ring to
1H-perimidine derivatives containing a functional group at position 6(7). Either 1,3,5-triazines in
polyphosphoric acid (PPA) [7] or a combination of 1,3,5-triazines with sodium azide in PPA [8] have been used
as reagents. The unsubstituted 1H-1,5,7-triazacyclopenta[cd]phenalene and derivatives of this heterocyclic
R
R
6
5 N
N7
N
NH
8
9
PhNO2, KOH
4
3
, 2 h
N 1
2
R1
O
R1
Ph
1a–e
a R = H, R1 = Ph; b R = Me, R1 = Ph; c R = R1 = Ph; d R = Me, R1 = H; e R = R1 = H
2a–e
_______
*To whom correspondence should be addressed, e-mail: alexaks05@rambler.ru.
1North Caucasus Federal University, 1a Pushkin St., Stavropol 355009, Russia.
2Department of Chemistry, University of Kansas and Center for Medicinal Libraries Development, 1255
Wescoe Hall Drive, Lawrence, KS 66049, U.S.A.; e-mail: mrubin@ku.edu.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 821-824, May, 2015. Original
article submitted February 17, 2014.
0009-3122/14/5005-0757©2014 Springer Science+Business Media New York
757

system with a substituent at positions 2 and 6 were obtained as a result. However, representatives of this class of
compounds with a substituent at the nitrogen atom in position 1 have remained unavailable to this time. Based
on previously successful work we decided to develop a method for their synthesis by direct peri annelation
using the previously unknown reaction between perimidine series carbonyl compounds and nitrobenzene.
It was found that refluxing the aldehydes and ketones 1a-e with nitrobenzene in the presence of base
gave the N-phenyl-1H-1,5,7-triazacyclopenta[cd]phenalenes 2a-e. We consider that this peri annelation reaction
occurs via a stage of reduction of the nitrobenzene by the starting compounds 1a-e to nitrosobenzene which also
takes part in the reaction according to the mechanism in the reaction given below. In confirmation of this
mechanism it was found that the product yields in this reaction did not exceed 45%. Loss of the target product
evidently occurs via a partial oxidation of the starting compounds 1a-e by the N-oxides formed in the process.
Along with this, exchange of the nitrobenzene for nitrosobenzene allows compound 2a to be obtained in a
higher yield (53%).
1a–e + PhNO2
PhNO + oxidation products
R
R
R
N
N
N
N
N
NH
OH–
~H+
1a–e
–H2O
–
N
O
H
R1
O
O
R1
O
R1
Ph–N=O
Ph
R
R
R
N
N
N
NH
N
NH
2a–e
+
oxidation
products
~H+
–OH–
1a–e
+
+
N
O
O
N
O
:
N
O
R1
R1
O
R1 Ph
Ph
Ph
The structure of compound 2a was confirmed unambiguously by correlation NMR spectroscopy
(Fig. 1).
Hence, on the basis of the reaction of benzoyl- and formylperimidines with nitrobenzene in the presence
of alkali we have developed an efficient method for the synthesis of novel representatives of the 1H-1,5,7-tri-
azacyclopenta[cd]phenalene system containing a phenyl substituent at position 1.
1H NMR and DEPTQ 13C NMR spectra and also the HSQC 1H–13C, HMBC 1H–13C, and HMBC 1H–15N
1
13
15
spectra were recorded on a Bruker Avance-III spectrometer at 400, 100, and 40 MHz (for the H, C, and N
nuclei, respectively). The solvents were: CDCl3 (1H NMR spectra of compounds 2c,e) or DMSO-d6 ( spectra of
the remaining compounds) with TMS as internal standard for 1H and 13C nuclei and with MeNO2 at 376.8 ppm
for the 15N nucleus. High-resolution mass spectra were recorded on a Bruker Maxis instrument using CI
(solution in MeCN, calibrant HCO2Na–HCO2H). Melting points were determined on a Khimlaborpribor PTP-M
apparatus. Monitoring of the reaction course and the purity of the products was carried out by TLC on Silufol
UV-254 plates using EtOAc–petroleum ether in varying ratios as eluent. The compounds obtained were purified
by flash chromatography (silica gel, L 5/40, eluent EtOAc–petroleum ether, 3:1).The starting compounds 1a-c
were prepared by method [9] and compounds 1d,e by method [10]. The physicochemical properties for the
758

starting materials were identical to those given in the studies [9] (compound 1a), in [11] (compounds 1b,c), and
in [10] (compounds 1d,e). Commercially available nitrobenzene and nitrosobenzene from Sigma-Aldrich were
used without additional purification.
H
6
N 5
N
7
H
H
H
4a
7a
4a1
4
3
8
9
2a
2a1
H
H
9a
1
N
2
– HSQC 1H–13C
– HMBC 1H–13C и 1H–15N
H
Fig. 1. Correlations in the HSQC 1H–13C, HMBC 1H–13C, and HMBC 1H–15N spectra of compound 2a.
1,2-Diphenyl-1H-1,5,7-triazacyclopenta[cd]phenalene (2a). A. A mixture of compound 1a (0.27 g,
1 mmol) and KOH (0.11 g, 2 mmol) in nitrobenzene (20 ml) was refluxed for 2 h. At the end of the reaction the
excess nitrobenzene was removed by steam distillation.
Using method A also gave compounds 2b-e. The compounds are obtained as dark-red crystals.
B. A mixture of compound 1a (0.27 g, 1 mmol), KOH (0.11 g, 2 mmol), and nitrosobenzene (0.32 g,
3 mmol) in ethylene glycol (20 ml) was refluxed for 2.5-3.0 h. At the end of the reaction the mixture was poured
into water, and the precipitate formed was filtered off.
1
Compound 2a. Yield 0.16 g (42%, method A), 0.18 g (53%, method B). Mp 187-189C. H NMR
spectrum, δ, ppm (J, Hz): 7.43-7.65 (10H, m, H Ph); 7.84 (1H, d, J = 9.2, H-4); 7.99 (1H, d, J = 8.9, H-8); 8.20
(1H, d, J = 8.9, H-9); 8.52 (1H, d, J = 9.2, H-3); 9.55 (1H, s, H-6). 13C NMR spectrum, δ, ppm: 114.3 (С-4а1);
114.5 (С-2а1); 120.0 (С-2a); 120.4 (С-8); 121.1 (С-9); 123.9 (С-4); 128.2 (2С); 128.7 (С-9a); 129.2; 129.3;
129.4 (2С); 130.3 (2С); 130.4 (С-2); 130.6 (2С); 131.6 (С-3); 137.5 (C-i 2-Ph); 137.9 (C-i 1-Ph); 148.5 (C-7a);
154.9 (C-4a); 155.7 (C-6). 15N NMR spectrum, δ, ppm: -93.3 (N-5,7); -205.7 (N-1). Found, m/z: 346.1351
[M+H]+. C24H16N3. Calculated, m/z: 346.1339.
6-Methyl-1,2-diphenyl-1H-1,5,7-triazacyclopenta[cd]phenalene (2b). Yield 0.17
g
(45%).
1
Mp 183-184C. H NMR spectrum, δ, ppm (J, Hz): 2.94 (3H, s, CH3); 7.41-7.62 (10H, m, H Ph); 7.73 (1H, d,
J = 9.2, H-4); 7.86 (1H, d, J = 8.9, H-8); 8.11 (1H, d, J = 8.9, H-9); 8.44 (1H, d, J = 9.2, H-3). 13C NMR
spectrum, δ, ppm: 27.6; 112.4; 114.3; 120.2; 120.3; 120.9; 124.0; 128.2 (2С); 128.4; 129.1; 129.2; 129.4 (2С);
130.3 (2С); 130.5; 130.6 (2С); 131.3; 137.5; 137.6; 149.2; 155.5; 164.7. Found, m/z: 360.1498 [M+H]+.
C25H18N3. Calculated, m/z: 360.1495.
1,2,6-Triphenyl-1H-1,5,7-triazacyclopenta[cd]phenalene (2c). Yield 0.13 g (36%). Mp 253-254C.
1H NMR spectrum, δ, ppm (J, Hz): 7.45-7.62 (13H, m, H Ph); 7.87 (1H, d, J = 9.0, H-4); 8.06 (1H, d, J = 9.0,
H-8); 8.37 (1H, d, J = 9.0, H-9); 8.50 (2H, d, J = 8.1, H-2,6 6-Ph); 8.62 (1H, d, J = 9.0, H-3). 13C NMR
spectrum, δ, ppm: 113.7; 114.1; 120.3; 120.5; 120.7; 124.1; 127.4 (2C); 128.1 (2C); 128.2 (2C); 128.4; 129.0;
129.2; 129.4 (2C); 130.2; 130.3 (2C); 130.5; 130.6 (2C); 131.4; 137.5; 137.8; 140.3; 148.7; 155.2; 161.8.
Found, m/z: 422.1659 [M+H]+. C30H20N3. Calculated, m/z: 422.1652
6-Methyl-1-phenyl-1H-1,5,7-triazacyclopenta[cd]phenalene (2d). Yield 0.13 g (30%). Mp 223-224C.
1H NMR spectrum, δ, ppm (J, Hz): 2.96 (3H, s, CH3); 7.41-7.63 (5H, m, H Ph); 7.89 (1H, d, J = 9.1,
759

H-4); 8.06 (1H, d, J = 8.9, H-9); 8.51 (1H, d, J = 9.1, H-3); 9.16 (1H, d, J = 8.9, H-8); 9.23 (1H, s, H-2). Found,
m/z: 284.1187 [M+H]+. C19H14N3. Calculated, m/z: 284.1182.
1-Phenyl-1H-1,5,7-triazacyclopenta[cd]phenalene (2e). Yield 0.10 g (26%). Mp 198-199C. 1H NMR
spectrum, δ, ppm (J, Hz): 7.52-7.77 (5H, m, H Ph); 8.35 (1H, d, J = 9.2, H-4); 8.63 (1H, d, J = 8.9, H-8); 8.67
(1H, d, J = 9.2, H-3); 8.81 (1H, d, J = 8.9, H-9); 9.53 (1H, s, H-2); 9.71 (1H, s, H-6). Found, m/z: 270.1029
[M+H]+. C18H12N3. Calculated, m/z: 270.1026.
This work was carried out in the framework of the project section of the State Assignment to Higher
Education Institutions (Russian Ministry of Education and Science) and was financially supported by the
Russian Foundation for Basic Research (grant 14-03-31327 mol_a).
REFERENCES
1.
W. Zhang, Z. Liu, S. Li, T. Yang, O. Zhang, L. Ma, X. Tian, H. Zhang, C. Huang, S. Zhang, J. Ju,
Y. Shen, and C. Zhang, Org. Lett., 14, 3364 (2012).
2.
3.
S. Nakadate, K. Nozawa, and T. Yaguchi, Heterocycles, 83, 1867 (2011).
M. D. Varney, C. L. Palmer, J. G. Deal, S. Webber, K. M. Welsh, C. A. Bartlett, C. A. Morse,
W. W. Smith, and C. A. Janson, J. Med. Chem., 38, 1892 (1995).
T. Stafforst and J. M. Stadler, Angew. Chem., Int. Ed., 52, 12448 (2013).
O. Vostrowsky and A. Hirsch, Chem. Rev., 106, 5191 (2006).
4.
5.
6.
7.
R. H. Xie, Chem. Phys. Lett., 310, 379 (1999).
A. V. Aksenov, N. A. Aksenov, A. S. Lyakhovnenko, and I. V. Aksenova, Zh. Org. Khim., 49, 1575
(2013). [Russ. J. Org. Chem., 49, 1555 (2013)].
8.
9.
A. V. Aksenov, A. S. Lyakhovnenko, A. V. Andrienko, and I. I. Levina, Tetrahedron. Lett., 51 2406
(2010).
I. V. Borovlev and O. P. Demidov, Khim. Geterotsikl. Soedin., 902 (2009). [Chem. Heterocycl. Compd.,
45, 721 (2009)].
10.
11.
A. V. Aksenov, I. V. Borovlev, A. S. Lyakhovnenko, and I. V. Aksenova, Zh. Org. Khim., 43, 1581
(2007). [Russ. J. Org. Chem., 43, 1579 (2007)].
S. V. Shcherbakov, D. A. Lobach, and A. V. Aksenov, Khim. Geterotsikl. Soedin., 327 (2014). [Chem.
Heterocycl. Compd., 50, 300 (2014)].
760