An original approach to the synthesis of 1,3,6,8-tetraazapyrenes

Full text of DOI:10.1007/s10593-010-0643-6

Chemistry of Heterocyclic Compounds, Vol. 46, No. 9, 2010
AN ORIGINAL APPROACH TO THE SYNTHESIS
OF 1,3,6,8-TETRAAZAPYRENES
A. V. Aksenov1*, A. S. Lyakhovnenko1,
N. Ts. Karaivanov1, and I. V. Aksenova1
Keywords: sodium azide, perimidines, PPA, 1,3,6,8-tetraazapyrenes, amination, peri annelation,
Schmidt reaction.
Methods have been developed for the synthesis of 1,3,6,8-tetraazapyrene based on the reaction of
1,4,5,8-tetraaminonaphthalene with formic acid [1] and the synthesis of 2,7-dimethyl-1,3,6,8-tetraazapyrene
based on the reaction of 6,7-diamino-2-methylperimidine with acetic anhydride [2]. These methods involve the
use of not readily available starting reagents and are not general. In the present work, we propose a method for
the synthesis of such compounds from available perimidine ketones 1a-c. Heating ketone 1a-c (1 mmol) and
NaN3 (0.26 g, 4 mmol) in PPA (2-3 g) at 70-80°C for 1 h and then at 100-110°C for 4 h with monitoring by
thin-layer chromatography leads to 1,3,6,8-tetraazapyrenes 4a-c in 31-44% yield. The PPA sample containing
87% P2O5 was prepared according to Uhlig [3].
This reaction involves the intermediate formation of amides 2a-c, whose amination using sodium azide
in PPA, as previously described for perimidines [4, 5], leads to dihydro derivatives 3a-c, which are oxidized by
atmospheric oxygen to give tetraazapyrenes 4a-c.
R
R
R
R
HN
HN
N
N
N
N
N
N
N
NH
O
N
NH
[O]
NaN3
PPA
NaN3
PPA
HN
R1
O
R1
R1
R1
1a–c
2a–c
3a–c
1–4 a R = R1 = Me, b R = R1 = Ph, c R = Ph, R1 = Me
4a–c
_______
* To whom correspondence should be addressed, e-mail: k-biochem-org@stavsu.ru.
1Stavropol State University, Stavropol 355009, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1418-1420, September, 2010.
Original article submitted June 3, 2010.
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0009-3122/10/4609-1146©2010 Springer Science+Business Media, Inc.

The 1H NMR spectra were taken on a WP-200 spectrometer at 200 MHz in DMSO-d6 with TMS as the
internal standard. The course of the reactions and purity of the products were monitored by thin-layer
chromatography on Silufol UV-254 plates using 1:1 ethyl acetate–ethanol as the eluent.
The reaction mixture was treated with 50 ml water, brought to pH 8-9 by adding ammonium hydroxide.
The precipitate formed was filtered off. The mother liquor was extracted with three 50-ml portions of butanol.
The solvent was evaporated. The residue was combined with the precipitate. The compounds obtained were
purified by recrystallization.
2,7-Dimethyl-1,3,6,8-tetraazapyrene (4a) was obtained in 36% yield (0.084 g); mp >300°C (butanol)
1
(mp >300°C [2]). H NMR spectrum, , ppm: 3.12 (6H, s, CH3); 8.62 (4H, s, H-4, H-5, H-9, H-10). Found, %:
C 71.94; H 4.23; N 23.83. C14H10N4. Calculated, %: C 71.78; H 4.30; N 23.92.
2,7-Diphenyl-1,3,6,8-tetraazapyrene (4b) was obtained in 31% yield (0.111 g); mp >300°C (butanol).
1H NMR spectrum, , ppm: 7.55 (6H, m, H-3, H-4, H-5 Ph); 8.58 (4H, s, H-4, H-5, H-9, H-10); 8.62 (4H, m,
H-2, H-6 Ph). Found, %: C 80.54; H 3.88; N 15.58. C24H14N4. Calculated, %: C 80.43; H 3.94; N 15.63.
2-Methyl-7-phenyl-1,3,6,8-tetraazapyrene (4c) was obtained in 44% yield (0.13 g); mp >300°C
1
(butanol). H NMR spectrum, , ppm (J, Hz): 2.89 (3H, s, CH3); 7.49 (3H, m, H-3, H-4, H-5 Ph); 8.40 (2H, d,
J = 9.4, H-5, H-9); 8.49 (2H, d, J = 9.4, H-4, H-10); 8.89 (2H, m, H-2, H-6 Ph). Found, %: C 77.12; H 4.02;
N 18.86. C19H12N4. Calculated, %: C 77.01; H 4.08; N 18.91.
This work was carried out with the financial support of the Russian Basic Research Fund
(Grant 10-03-00193a).
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