Chemistry of Heterocyclic Compounds

, Volume 48, Issue 8, pp 1275–1277

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


  • A. S. Lyakhovnenko
    • North Caucasus Federal University
  • A. S. Kolesnikova
    • North Caucasus Federal University
  • I. V. Goncharov
    • North Caucasus Federal University
  • I. V. Aksenova
    • North Caucasus Federal University
    • North Caucasus Federal University

DOI: 10.1007/s10593-012-1133-9

Cite this article as:
Lyakhovnenko, A.S., Kolesnikova, A.S., Goncharov, I.V. et al. Chem Heterocycl Comp (2012) 48: 1275. doi:10.1007/s10593-012-1133-9


benzoyl hydrazineperimidinespolyphosphoric acidsodium azide1,2,6,8-tetraazapyrenesperi-annelation

Azapyrenes are used as organic luminophores and dyes, and they include compounds with high cytostatic and analgesic activity [13]. 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 70-80°C, and further with benzoyl hydrazine in the ratio 1:3:1 at 125-135°C 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 70-80°C 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 125-135°C, 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.
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 194-195°C. Rf 0.6 (EtOAc– EtOH, 1:1). IR spectrum, ν, cm-1: 3420 (NH2). 1H NMR spectrum, δ, 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 182-183°C. Rf 0.6 (EtOAc–EtOH, 1:1). IR spectrum, ν, cm-1: 3407 (NH2). 1H NMR spectrum, δ, 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 215-216°C. Rf 0.42 (EtOAc). IR spectrum, ν, cm-1: 3436 (NH2). 1H NMR spectrum, ν, 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.

This work was carried out with the financial support of the Russian Foundation for Basic Research (grant 10-03-00193a).

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© Springer Science+Business Media New York 2012