Unusual reaction of 1h-perimidines with sodium azide and benzoyl hydrazine in polyphosphoric acid

Full text of DOI:10.1007/s10593-012-1133-9

Chemistry of Heterocyclic Compounds, Vol. 48, No. 8, November, 2012 (Russian Original Vol. 48, No. 8, August, 2012)
UNUSUAL REACTION OF 1H-PERIMIDINES WITH
SODIUM AZIDE AND BENZOYL HYDRAZINE IN
POLYPHOSPHORIC ACID
A. S. Lyakhovnenko1, A. S. Kolesnikova1, I. V. Goncharov1,
I. V. Aksenova1, and A. V. Aksenov1*
Keywords: benzoyl hydrazine, perimidines, polyphosphoric acid, sodium azide, 1,2,6,8-tetraazapyrenes,
peri-annelation.
Azapyrenes are used as organic luminophores and dyes, and they include compounds with high
cytostatic and analgesic activity [1-3]. None the less there are a limited number of methods for the synthesis of
such compounds, particularly those with functional groups. In this work, we propose a one-pot method for
preparing the 10-amino-1,2,6,8-tetraazapyrenes 8a-c, based on our recently discovered method for the
amination of perimidines with sodium azide in polyphosphoric acid (PPA) [4, 5].
It was found that a reaction of perimidines 1a-c with NaN3 in PPA at 70-80ºC, and further with benzoyl
hydrazine in the ratio 1:3:1 at 125-135ºC gave the previously unknown 10-amino-1,2,6,8-tetraazapyrenes 8a-c
in 34-41% yields.
The reaction scheme, as reported in the studies [4, 5], includes the formation of the intermediates 2a-c
which are acylated by benzoyl hydrazine to give compounds 3a-c (found in equilibrium with 4a-c). Through an
intramolecular nucleophilic substitution the latter are converted to the 1,6-dihydro-1,2,6,8-tetraazapyrenes 5a-c.
These compounds are aminated by a scheme similar to that proposed for the amination of perimidines. After
hydrolysis and, likely, oxidation of the dihydro derivatives 7a-c by atmospheric oxygen, they are converted to
the amines 8a-c.
IR spectra were recorded on a UR-20 instrument using KBr pellets. 1H NMR spectra were recorded on a
Bruker WP-200 instrument (200 MHz) using DMSO-d6 with TMS as internal standard. Elemental analysis was
carried out on a KOVO CHN-1 CHN analyzer. Melting points were determined on a PTP-M apparatus
(Khimlaborpribor). Monitoring of the reaction course and the purity of the synthesized compounds was carried
out on Silufol UV-254 plates with EtOAc–EtOH (1:1) as eluent. PPA with an 86% content of P2O5 was
prepared by the method [6].
10-Amino-3-phenyl-1,2,6,8-tetraazapyrenes 8a-c (General Method). A mixture of perimidine 1a-c
(1 mmol) and NaN3 (0.13 g, 2 mmol) in 86% PPA (2-3 g) was heated at 70-80ºC for 2 h with vigorous stirring. An
additional portion of sodium azide (0.065 g, 1 mmol) was added and heating was continued for another 2 h.
Benzoyl hydrazine (0.136 g, 1 mmol) was then added, the reaction mixture temperature was raised to 125-135ºC,
_______
*To whom correspondence should be addressed, e-mail: alexaks05@rambler.ru.
1North Caucasus Federal University, 1a Pushkin St., Stavropol 355009, Russia.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1366-1368, August, 2012.
Original article submitted April 4, 2012.
0009-3122/12/4808-1275©2012 Springer Science+Business Media New York
1275

and heating was continued for 5 h. The reaction mixture was cooled, poured into water (50 ml), neutralized with
ammonia solution, and extracted with BuOH (5×50 ml). The butanol was evaporated, and the residue was
separated by flash chromatography. The obtained compounds 8a-c were recrystallized from EtOAc.
R
R
R
O
NH2
NH
N
NH
NH
N
N
N
Ph
NaN3
PPA
H
PPA
1a–c
NH
NH
Ph
N
N
N
N
[PPA]
[PPA]
N
2a–c
NH2
3a–c
R
R
R
NH
HN
N
NH
N
N
N
NaN3
PPA
–[PPA]NH2
–N2
N
N
H
N
HN
HN
N
Ph
[PPA]
N
H
N
N
5a–c
Ph
[PPA]
N
Ph
6a–c
NH2
4a–c
R
R
N
N
N
HN
HN
N
[O]
H2O
–PPA
–N2
H2N
H2N
N
Ph
N
Ph
8a–c
7a–c
a R = H, b R = Me, c R = Ph
10-Amino-3-phenyl-1,2,6,8-tetraazapyrene (8a). Yield 0.119 g (40%); mp 194-195ºC. Rf 0.6 (EtOAc–
1
EtOH, 1:1). IR spectrum, , cm-1: 3420 (NH2). H NMR spectrum, , ppm (J, Hz): 7.30 (2H, br. s, NH2); 7.51
(1H, s, H-9); 7.65-7.72 (3H, m, H-3,4,5 Ph); 7.91 (2H, d, J = 7.5, H-2,6 Ph); 8.39 (1H, d, J = 9.4, H-4); 8.83
(1H, d, J = 9.4, H-5); 9.93 (1H, s, H-7). Found, %: C 72.88; H 3.68; N 23.44. C18H11N5. Calculated, %: C 72.72;
H 3.73; N 23.55.
10-Amino-7-methyl-3-phenyl-1,2,6,8-tetraazapyrene (8b). Yield 0.127 g (41%); mp 182-183ºC.
1
Rf 0.6 (EtOAc–EtOH, 1:1). IR spectrum, , cm-1: 3407 (NH2). H NMR spectrum, , ppm (J, Hz): 3.11 (3H, s,
CH3); 7.36 (2H, br. s, NH2); 7.51 (1H, s, H-9); 7.65-7.71 (3H, m, H-3,4,5 Ph); 7.93 (2H, d, J = 7.6, H-2,6 Ph);
8.42 (1H, d, J = 9.4, H-4); 8.83 (1H, d, J = 9.4, H-5). Found, %: C 73.42; H 4.19; N 22.41. C19H13N5.
Calculated, %: C 73.30; H 4.21; N 22.49.
10-Amino-3,7-diphenyl-1,2,6,8-tetraazapyrene (8c). Yield 0.127 g (34%); mp 215-216ºC. Rf 0.42
(EtOAc). IR spectrum, , cm-1: 3436 (NH2). 1H NMR spectrum, , ppm (J, Hz): 7.45 (2H, br. s, NH2); 7.52 (1H,
s, H-9); 7.60-7.70 (6H, m, H-3,4,5 (3,7-Ph)); 7.93 (2H, d, J = 7.6, H-2,6 (3-Ph)); 8.46 (1H, d, J = 9.4, H-4); 8.84
(1H, d, J = 9.4, H-5); 8.95 (2H, d, J = 8.2, H-2,6 (7-Ph)). Found, %: C 77.32; H 3.98; N 18.70. C24H15N5.
Calculated, %: C 77.20; H 4.05; N 18.75.
1276

This work was carried out with the financial support of the Russian Foundation for Basic Research
(grant 10-03-00193a).
REFERENCES
1.
2.
A. D. Andricopolo, L. A. Muller, V. C. Filho, G.-N. R. J. Cani, and R. A. Yunes, Farmaco, 55, 319
(2000).
S. Roknic, L. Glavas-Obrovac, I. Karner, I. Piantanida, M. Zinic, and K. Pavelic, Chemotherapy, 46,
143 (2000).
3.
4.
A. M. Brun and A. Harriman, J. Am. Chem. Soc., 113, 8153 (1991).
A. V. Aksenov, A. S. Lyakhovnenko, and N. Ts. Karaivanov, Khim. Geterotsikl. Soedin., 1091 (2009).
[Chem. Heterocycl. Compd., 45, 871 (2009)].
5.
6.
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).
1277