Letters to the editor: New three-component reaction of perimidines with sodium azide and sodium nitrite in poly-phosphoric acid

Full text of DOI:10.1007/s10593-012-1043-x

Chemistry of Heterocyclic Compounds, Vol. 48, No. 4, July, 2012 (Russian Original Vol. 48, No. 4, April, 2012)
LETTERS TO THE EDITOR
NEW THREE-COMPONENT REACTION OF PERIMIDINES
WITH SODIUM AZIDE AND SODIUM NITRITE IN POLY-
PHOSPHORIC ACID
A. S. Lyakhovnenko1, A. V. Aksenov1*, N. A. Aksenov1,
V. I. Goncharov2, and I. V. Aksenova1
Keywords: perimidines, polyphosphoric acid, sodium azide, sodium nitrite, 1,2,5,7-tetraazacyclo-
penta[cd]phenalenes, amination, peri-annelation.
Polynuclear aromatic and heteroaromatic compounds, including compounds with peri-annelated penta-
and hexa-membered rings, have considerable practical value. Effective medications [1, 2] and luminescent
intercalators [3, 4] have been created based on them.
We have previously developed a series of methods for peri-annelation of pyrrole [1, 5-7] and furan [5]
rings to naphthalene derivatives. At the same time, there are only a few examples of the peri-annelation of the
pyrazole nucleus [5, 8]. In the present work, we have developed a method for the synthesis of compounds with
such fragments based on the electrophilic amination of arenes with sodium azide in polyphosphoric acid (PPA)
[9-11] and nitrosation of the heterocyclic intermediates with sodium nitrite.
We have established that heating of the perimidines 1a-c with a threefold excess of sodium azide and a
twofold molar excess of NaNO2 in PPA (86% content of P2O5) gave 1,2,5,7-tetraazacyclopenta[cd]phenalenes
2a-c in 46-52% yields.
The reaction can be carried with a simultaneous mixture of all components, but in this case the yields
are somewhat lower (37-41%).
The mechanism of the reaction probably includes the formation of the intermediate compounds 3a-c
from the perimidines 1a-c and sodium azide [9-11]. Subsequent nitrosation of these compounds at the nitrogen
atom leads to the intermediates 4a-c, which by loss of PPA and a molecule of nitrogen, are converted into the N-
nitroso derivatives 5a-c. Cyclization of the latter gives the required compounds 2a-c.
1H NMR spectra were recorded with a Bruker WP-200 (200 MHz) spectrometer with TMS as internal
standard. IR spectra were recorded with a UR-20 spectrophotometer using KBr pellets. The course of the
reactions and the purity of the products were monitored by TLC on Silufol UV-254 plates in ethyl acetate. PPA
with 86% P2O5 content was prepared by a known method [12].
______
*To whom correspondence should be addressed, e-mail: alexaks05@rambler.ru.
1Stavropol State University, 1a Pushkin St., Stavropol 255009, Russia.
2Stavropol State Medical Academy, 310 Mir St., Stavropol 355017, Russia; e-mail: sgma@statel.stavropol.ru.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 726-728, April, 2012. Original article
submitted January 31, 2012.
0009-3122/12/4804-0677©2012 Springer Science+Business Media, Inc.
677

1,2,5,7-Tetraazacyclopenta[cd]phenalenes 2a-c (General Method). A. A mixture of perimidine 1a-c
(1.00 mmol), NaN3 (0.07 g, 1.07 mmol) in 86% PPA (2-3 g) was heated with vigorous stirring for 4 h at 80-
90°C and for 1 h at 110°C. NaNO2 (0.14 g, 2.00 mmol) was then added, and stirring continued for 2 h at 110°C.
The reaction mixture was poured into water (30 ml), neutralized with ammonia solution, and extracted with
benzene (630 ml), the solvent was evaporated, and the residue was recrystallized from benzene.
B. The same components in the same quantities as in method A were mixed simultaneously and heated
for 4 h at 80-90°C and for 3 h at 110°C. The products were isolated as in method A.
R
R
R
N
N
N
N
NaN3
PPA
N
NaNO2
H+
HN
O
O
O
R
N+ N
NH
1a–c
P
N
OH
P
N
N
N
[PPA]
O
[PPA]
R
O
OH
3a–c
4a–c
R
R
N
N
HN
N
HN
O
N
HN
N
H+
– H+
– N2
– PPA
– H2O
HO+
N
NH
N
NH
N
NH
HO
N
NH
5a–c
6a–c
7a–c
2a–c
a R = H, b R = Me, c R = Ph
1H-1,2,5,7-Tetraazacyclopenta[cd]phenalene (2a). Yield 0.101 g (52%) (method A), 0.080 g (41%)
(method B); mp 233-235°C (decomp., benzene) (mp 233°C (decomp., benzene) [8]). IR spectrum, ν, cm-1: 3410
(NH). 1H NMR spectrum was identical to the published one [8].
6-Methyl-1H-1,2,5,7-tetraazacyclopenta[cd]phenalene (2b). Yield 0.108 g (52%) (method A), 0.085 g
(41%) (method B); mp 231-233°C (decomp., benzene) (mp 231°C (decomp., benzene) [8]). IR spectrum, ν, cm-1:
3488 (NH). 1H NMR spectrum was identical to the published one [8].
6-Phenyl-1H-1,2,5,7-tetraazacyclopenta[cd]phenalene (2c). Yield 0.124 g (46%) (method A), 0.100 g
1
(37%) (method B); mp 258-260°C (decomp., benzene). IR spectrum, ν, cm-1: 3407 (NH). H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 7.18 (1H, d, J = 9.9, H-9); 7.49-7.55 (3H, m, H-3,4,5 Ph); 7.94 (1H, d, J = 9.9, H-8);
8.33 (1H, d, J = 9.5, H-4); 8.49-8.51 (2H, m, H-2,6 Ph); 9.22 (1H, d, J = 9.5, H-3); 12.70 (1H, br. s, NH).
Found, %: C 75.62; H 3.68; N 20.70. C17H10N4. Calculated, %: C 75.54; H 3.73; N 20.73.
This work was carried out with a grant from the Russian Foundation for Basic Research (grant 10-03-
00193a).
REFERENCES
1.
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. Jansen, J. Med. Chem., 38, 1892 (1995).
678

2.
S. Roknić, Lj. Glavaš-Obrovac, I. Karner, I. Piantanida, M. Žinić, and K. Pavelić, Chemotherapy, 46,
143 (2000).
3.
4.
5.
6.
H. C. Becker and B. Norden, J. Am. Chem. Soc., 119, 5798 (1997).
H. Ikeda, K. Fuji, and K. Tanaka, Bioorg. Med. Chem. Lett., 6, 101 (1996).
V. V. Mezheritskii and V. V. Tkachenko, Adv. Heterocycl. Chem., 51, 1 (1990).
A. V. Aksenov, A. S. Lyakhovnenko, A. V. Andrienko, and I. I. Levina, Tetrahedron Lett., 51. 2406
(2010).
7.
8.
A. V. Aksenov, N. A. Aksenov, A. E. Tsys', and O. N. Nadein, Khim. Geterotsikl. Soedin., 1909 (2010).
[Chem. Heterocycl. Compd., 46, 1547 (2010)].
A. V. Aksenov, A. S. Lyakhovnenko, A. N. Spitsyn, and N. V. Aksenov, Khim. Geterotsikl. Soedin.,
1429 (2011). [ Chem. Heterocycl. Compd., 47, 1180 (2011)].
9.
A. V. Aksenov, N. A. Aksenov, O. N. Nadein, and Yu. I. Smushkevich, Obzornyi Zh. po Khimii, 1, 350
(2011) [Review Journal of Chemistry, 1, 359 (2011)].
10.
11.
12.
A. V. Aksenov, A. S. Lyakhovnenko, and N. Ts. Karaivanov, Khim. Geterotsikl. Soedin., 1091 (2009).
[Chem. Heterocycl. Compd., 45, 871 (2009)].
A. V. Aksenov, A. S. Lyakhovnenko, N. Ts. Karaivanov, and I. I. Levina, Khim. Geterotsikl. Soedin.,
591 (2010). [Chem. Heterocycl. Compd., 46, 468 (2010)].
F. Uhlig, Angew. Chem., 66, 435 (1954).
679