Synthesis of 1,2,6,8-tetraazapyrenes by the reaction of aldehydes and ketones of 1H-perimidine series with diethyl azodicarboxylate in polyphosphoric acid

Full text of DOI:10.1007/s11172-013-0153-7

Russian Chemical Bulletin, International Edition, Vol. 62, No. 4, pp. 1125—1126, April, 2013
1125
Letters to the Editor
Synthesis of 1,2,6,8ꢀtetraazapyrenes by the reaction of aldehydes and ketones
of 1Hꢀperimidine series with diethyl azodicarboxylate
in polyphosphoric acid
A. M. Zhirov, A. S. Kolesnikova, I. V. Aksenova, A. S. Lyakhovnenko, and A. V. Aksenov
North Caucasus Federal University,
1a ul. Pushkina, 355009 Stavropol´, Russian Federation.
Fax: +7 (865) 235 4033. Eꢀmail: kꢀbiochemꢀorg@stavsu.ru
Scheme 1
Azapyrenes are used as fluorescent DNA intercallaꢀ
tors1, among them are also found compounds possessing
cytotoxic2 and analgesic activity.3 Nevertheless, only limꢀ
ited number of methods for the synthesis of such comꢀ
pounds are known at present, and the synthesis of 1,2,6,8ꢀ
tetraazapyrenes is described only in one work.4
In the present work, we suggest a method for the synꢀ
thesis of 1,2,6,8ꢀtetraazapyrenes based on the reaction of
6(7)ꢀformyl(benzoyl)perimidines with diethyl azodicarꢀ
boxylate.
Lewis5—8 or Brønsted acids8,9 were used as catalysts in
the reaction of azodicarboxylates with arenes.
We showed that the reaction of 6(7)ꢀformyl(benzoꢀ
yl)perimidines 1a—c with a twoꢀfold excess of diethyl
azodicarboxylate (2) in polyphosphoric acid (PPA) at
80—90 C with subsequent treatment of the reaction mixꢀ
ture with water and reflux of the solution formed led to
1,2,6,8ꢀtetraazapyrenes 3a—c in 32—37% yields (Scheme 1).
A mechanism suggested for this transformation
(Scheme 2) includes the Michael addition of azo comꢀ
pound 2 to perimidines 1a—c, resulting in hydrazines 5,
which cyclize with the formation of dihydro derivatives of
tetraazapyrenes 6. The hydrolysis and oxidation of the
Compound
1a, 3a
1b, 3b
R
H
Ph
H
R´
H
H
1c, 3c
Ph
latter, probably, with atmospheric oxygen gives the target
tetraazapyrenes 3a—c.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 1125—1126, April, 2013.
1066ꢀ5285/13/6204ꢀ1125 © 2013 Springer Science+Business Media, Inc.

1126
Russ.Chem.Bull., Int.Ed., Vol. 62, No. 4, April, 2013
Zhirov et al.
Scheme 2
chromatography was carried out on L 5/40 silica gel, eluent
ethyl acetate—ethanol, 9 : 1.
1,2,6,8ꢀTetraazapyrene (3a). The yield was 0.066 g (32%).
M.p. 142—144 C (from ethyl acetate; Ref. 4: m.p. 142—144 C).
The NMR spectrum is consistent with that given in the work.4
7ꢀPhenylꢀ1,2,6,8ꢀtetraazapyrene (3b). The yield was 0.104 g
(37%). M.p. 244—246 C (from ethyl acetate; Ref. 4: m.p.
244—246 C). The NMR spectrum is consistent with that given
in the work.4
3ꢀPhenylꢀ1,2,6,8ꢀtetraazapyrene (3c). The yield was 0.102 g
(36%). M.p. 236—238 C (from ethyl acetate). 1H NMR
(DMSOꢀd6), : 7.47 (m, 3 H, C(3)Ph, mꢀ and pꢀH); 8.01 (dd,
2 H, C(3)Ph, oꢀH, J = 7.6 Hz, J = 1.2 Hz); 8.56 (d, 1 H, H(10),
J = 9.5 Hz); 8.68 (d, 1 H, H(4), J = 9.4 Hz); 8.76 (d, 1 H, H(5),
J = 9.4 Hz); 9.06 (d, 1 H, H(9), J = 9.5 Hz); 10.06 (s, 1 H, H(7)).
Found (%): C, 76.67; H, 3.52; N, 19.81. C18H10N4. Calculatꢀ
ed (%): C, 76.58; H, 3.57; N, 19.85.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 10ꢀ03ꢀ
00193a).
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In conclusion, the reaction of 6(7)ꢀformyl(benzoyl)ꢀ
perimidines with diethyl azodicarboxylate in PPA leads to
1,2,6,8ꢀtetraazapyrenes. We plan to further study the genꢀ
erality of this reaction with respect to other azaphenalenes.
Synthesis of 1,2,6,8ꢀtetraazapyrenes 3a—c (general proceꢀ
dure). A corresponding 6(7)ꢀformyl(benzoyl)perimidine 1a—c
(1 mmol) was dissolved in PPA (2—3 g), followed by the addiꢀ
tion of diethyl azodicarboxylate (2) (0.35 g, 2 mmol) and vigorꢀ
ous stirring at 80—90 C for 3 h. The reaction mixture was poured
into cold water (30 mL) with stirring and refluxed for 1 h. Then,
it was treated with aqueous ammonia to pH ~8. A precipitate
formed was filtered off, the mother liquor was extracted with
butanol (3×50 mL). Butanol was evaporated, the residue was
combined with the filtered residue, the solvent was evaporated.
Compounds were purified by flashꢀchromatography.
NMR spectra were recorded on a Bruker DRXꢀ500 specꢀ
trometer (500 MHz) using SiMe4 as an internal standard. The
reaction progress and individuality of the compounds syntheꢀ
sized were performed on Silufol UVꢀ254 plates, using chloroꢀ
form as the solvent. 6(7)ꢀFormyl(benzoyl)perimidines were obꢀ
tained according to the procedures published earlier.10,11 Flashꢀ
11. A. V. Aksenov, I. V. Borovlev, A. S. Lyakhovnenko, I. V.
Aksenova, Russ. J. Org. Chem. (Engl. Transl.), 2007, 43, 1581
[Zh. Org. Khim. 2007, 43, 1581].
Received November 8, 2012;
in revised form February 22, 2013