Synthesis of 1,3-diazapyrenes by the reaction of 1H-perimidines with 1,3-dicarbonyl compounds

Article abstract of DOI:10.1007/s11172-009-0108-1

A method for the synthesis of 1, 3-diazapyrenes has been developed based on the reaction of 1H-perimidines with 1,3-dicarbonyl compounds in polyphosphoric or 70% aq. sulfuric acid.

Full text of DOI:10.1007/s11172-009-0108-1

Russian Chemical Bulletin, International Edition, Vol. 58, No. 4, pp. 859—861, April, 2009
859
Synthesis of 1,3ꢀdiazapyrenes by the reaction of 1Hꢀperimidines
with 1,3ꢀdicarbonyl compounds
A. V. Aksenov, I. V. Aksenova, A. S. Lyakhovnenko, and D. A. Lobach
Stavropol State University,
1a ul. Pushkina, 355009 Stavropol, Russian Federation.
Fax: +7 (865) 235 4033. Eꢀmail: kꢀbiochemꢀorg@stavsu.ru
A method for the synthesis of 1,3ꢀdiazapyrenes has been developed based on the reaction of
1Hꢀperimidines with 1,3ꢀdicarbonyl compounds in polyphosphoric or 70% aq. sulfuric acid.
Key words: perimidines, 1,3ꢀdiazapyrene.
Scheme 1
Azapyrenes belong to the class of multinuclear hetꢀ
eroaromatic compounds, which are of interest in both theꢀ
oretical (aromaticity, mechanism of electrophilic and nuꢀ
cleophilic substitution, stability of radical ions, etc.), and
applied aspects.1 For example, intercalating properties of
4(9)ꢀ (see Refs 2 and 3) and 2,7ꢀdiazapyrene4—6 derivaꢀ
tives are under active study, results on investigation of
their biological activity are published7—10 and their use in
supramolecular chemistry is described.11 No more than
20 azapyrene structures from almost 300 possible have
been synthesized so far.12 A few existing methods for the
synthesis of 1,3ꢀdiazapyrenes1,12,13 allow one to obtain
them either without substituents at positions 6 and 8 or
with an aryl substituent. The most efficient method is based
on a threeꢀcomponent reaction of 1Hꢀperimidines 1 with
carbonyl compounds and 1,3,5ꢀtriazines in polyphosphoric
acid (PPA) with 86% content of P2O5 (Scheme 1).14 The
use of expensive and, hence, poorly available 1,3,5ꢀtriꢀ
azines is a disadvantage of this method.
R = H, Me, Ph; R´ = H, Me, Ph; R″ = H, Me, Ph;
In the present work, a simple and efficient method for
the synthesis of 1,3ꢀdiazapyrenes based on the reaction of
1Hꢀperimidines 1 with 1,3ꢀdicarbonyl compounds is
suggested.
X = H, COMe, CO2Et
Scheme 2
Earlier,13 it has been reported that the reaction of
1Hꢀperimidines 1 with acetylacetone 2a in PPA with 80%
content of P2O5 begins only at temperatures higher 100 °C
and leads to 4(9)ꢀacetylperimidine (3) in 10% yield
(Scheme 2). No formation of 1,3ꢀdiazapyrenes (4) was
observed under these conditions.13
Based on the reported results,14 we suggested that such
a result is due to the reaction conditions. In fact, a reducꢀ
tion of the temperature to 70—75 °C (PPA with 80% conꢀ
tent of P2O5) allows one to obtain diazapyrene 4a in 71%
yield (Scheme 3). The yield of ketone 3 under these condiꢀ
tions was 11%.
Earlier,15 it has been reported that, depending on the
amount of P2O5 (80 or 86%) in PPA, the regioselectivity
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 841—843, April, 2009.
1066ꢀ5285/09/5804ꢀ0859 © 2009 Springer Science+Business Media, Inc.

860
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
Aksenov et al.
Scheme 3
extracted with ethyl acetate, the solvent was evaporated. The
product was recrystallized from ethyl acetate.
Reaction in sulfuric acid (method B). A mixture of perimidine
1 (1 mmol), dicarbonyl compound 2 (2.5 mmol), and 70% aq.
sulfuric acid (10 mL) was heated for 3—4 h at 95—100 °C, then
poured into some cold water, which was made basic with aq.
ammonia to pH ~8. A precipitate formed was filtered off. The
filtrate was additionally extracted with ethyl acetate, the solvent
was evaporated. The product was recrystallized from ethyl acetate.
4(9)ꢀAcetylperimidine (3). The yield was 0.023 g (11%) (80%
P2O5), 0.054 g (26%) (86% P2O5) (method A, from perimidine
and acetylacetone). M.p. 201—202 °C (ethyl acetate) (cf. Ref. 13:
m.p. 201—202 °C). Found (%): C, 74.41; H, 4.73; N, 13.27.
C13H10N2O. Calculated (%): C, 74.27; H, 4.79; N, 13.32.
1H NMR, δ: 2.56 (s, 3 H, CH3CO); 6.99 (d, 1 H, H(7), J = 9.1 Hz);
7.11 (dd, 1 H, H(4), J = 7.6 Hz, J = 1.1 Hz); 7.26 (dd, 1 H, H(6),
J = 8.1 Hz, J = 1.1 Hz); 7.44 (d, 1 H, H(8), J = 9.1 Hz); 7.51
(dd, 1 H, H(5), J = 7.6 Hz, J = 8.1 Hz); 7.68 (d, 1 H, H(2),
J = 3.1 Hz); 12.60 (br.s, 1 H, NH...O=).
Comꢀ
pound
1a
1b
1c
2a
2b
2c
4a
4b
4c
4d
4e
R
R´
R″
H
Me
Ph
—
—
—
H
H
H
Me
Me
Ph
—
—
—
—
—
—
Me
Me
Ph
Me
Me
Ph
Me
Ph
Ph
Me
Ph
Ph
Me
Ph
Ph
Me
Ph
Ph
6,8ꢀDimethylꢀ1,3ꢀdiazapyrene (4a). The yield was 0.165 g
(71%) (80% P2O5), 0.144 g (62%) (86% P2O5) (method A), 0.19 g
(82%) (method B). M.p. 207—209 °C (ethyl acetate) (cf. Ref. 14:
m.p. 207—209 °C). Found (%): C, 82.89; H, 5.15; N, 11.96.
C
16H12N2. Calculated (%): C, 82.73; H, 5.21; N, 12.06. 1H NMR
is analogous to that given in Ref. 14.
4f
6ꢀMethylꢀ8ꢀphenylꢀ1,3ꢀdiazapyrene (4b). The yield was 0.23 g
(79%) (method B). M.p. 198—199 °C (ethyl acetate) (cf. Ref. 13:
m.p. 198—199 °C). Found (%): C, 85.79; H, 4.72; N, 9.49.
C21H14N2. Calculated (%): C, 85.69; H, 4.79; N, 9.52. 1H NMR
is analogous to that given in Ref. 13.
of the reaction of compound 1 with unsaturated carboxylꢀ
ic acids can change. Therefore, a change in regioselectiviꢀ
ty of the reaction of compound 1 with 1,3ꢀdicarbonyl comꢀ
pounds could have been also expected. It turned out that
an increase in the content of P2O5 to 86% at the same
temperature leads to a decrease in the content of diazapyꢀ
rene 4a. Its yield was 62%, the yield of ketone 3, 26%.
To sum up, an increase in the concentration of P2O5
promotes cleavage of the diketone and side acylation of
1Hꢀperimidines 1. The running the reaction in 100% aq.
orthophosphoric acid or more available 70% aqueous sulꢀ
furic acid allows one to completely avoid the formation of
the acylation products and increase the yield of diazapyꢀ
rene 4a to 82%. This reaction can be applied to other
1,3ꢀdicarbonyl compounds.
6,8ꢀDiphenylꢀ1,3ꢀdiazapyrene (4c). The yield was 0.21 g
(59%) (method A, 80% P2O5), 0.29 g (82%) (method B). M.p.
175—176 °C (ethyl acetate) (cf. Ref. 13: m.p. 175—176 °C).
Found (%): C, 87.81; H, 4.46; N, 7.73. C26H16N2. Calculated (%):
1
C, 87.62; H, 4.52; N, 7.86. H NMR is analogous to that given
in Ref. 13.
2,6,8ꢀTrimethylꢀ1,3ꢀdiazapyrene (4d). The yield was 0.11 g
(45%) (method A, 80% P2O5), 0.19 g (77%) (method B). M.p.
241—243 °C (ethyl acetate). Found (%): C, 83.07; H, 5.66;
N, 11.27. C17H14N2. Calculated (%): C, 82.90; H, 5.73; N, 11.37.
1H NMR, δ: 2.96 (s, 3 H, Me(2)); 3.05 (s, 6 H, Me(6), Me(8));
7.86 (s, 1 H, H(7)); 8.17 (d, 2 H, H(5), H(9), J = 9.5 Hz); 8.71
(d, 2 H, H(4), H(10), J = 9.5 Hz).
2ꢀMethylꢀ6,8ꢀdiphenylꢀ1,3ꢀdiazapyrene (4e). The yield was
0.19 g (51%) (method A, 80% P2O5), 0.25 g (67%) (method B).
M.p. 182—183 °C (ethyl acetate) (cf. Ref. 13: m.p. 182—183 °C).
Found (%): C, 87.67; H, 5.09; N, 7.64. C27H18N2. Calculatꢀ
ed (%): C, 87.54; H, 4.90; N, 7.56. 1H NMR is analogous to that
given in Ref. 13.
In conclusion, we developed a method for the syntheꢀ
sis of 1,3ꢀdiazapyrenes based on the reaction of 1Hꢀperiꢀ
midines with 1,3ꢀdicarbonyl compounds.
Experimental
2,6,8ꢀTriphenylꢀ1,3ꢀdiazapyrene (4f). The yield was 0.23 g
(53%) (method A, 80% P2O5), 0.31 g (72%) (method B). M.p.
267—268 °C (ethyl acetate) (cf. Ref. 13: m.p. 267—268 °C).
Found (%): C, 88.96; H, 4.81; N, 6.35. C32H20N2. Calculatꢀ
ed (%): C, 88.86; H, 4.66; N, 6.48. 1H NMR is analogous to that
given in Ref. 13.
1
H NMR spectra were recorded on a Bruker WPꢀ200 specꢀ
trometer (200 MHz) using Me4Si as the internal standard and
CDCl3 as the solvent. Perimidine,16 2ꢀphenylperimidine,16
2ꢀmethylperimidine,16 PPA with 80% and 86% content of P2O5
17
were obtained according to the specified procedures.
Reaction in polyphosphoric acid (method A). A mixture of
perimidine 1 (1 mmol), dicarbonyl compound 2 (2.5 mmol), and
polyphosphoric acid (3—4 g) (with 80 or 86% content of P2O5)
was heated for 3—4 h at 70—75 °C, then poured into some cold
water, which was made basic with aq. ammonia to pH ~8.
A precipitate formed was filtered off. The filtrate was additionally
References
1. I. V. Borovlev, O. P. Demidov, Khim. Geterotsikl. Soꢀ
edin., 2003, 1612 [Chem. Heterocycl. Compd. (Engl. Transl.),
2003, 1417].

Synthesis of 1,3ꢀdiazapyrenes
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 4, April, 2009
861
2. I. Piantanida, V. Tomisic, M. Zinic, J. Chem. Soc., Perkin
Trans. 2, 2000, 375.
3. B. S. Palm, I. Piantanida, M. Zinic, H.ꢀJ. Schneider,
J. Chem. Soc., Perkin Trans. 2, 2000, 385.
4. H.ꢀC. Becker, B. Norden, J. Am. Chem. Soc., 1997,
119, 5798.
5. H.ꢀC. Becker, A. Broo, B. Norden, J. Phys. Chem., 1997,
101, 8853.
6. A. M. Brun, A. Harriman, J. Am. Chem. Soc., 1991, 113, 8153.
7. A. M. Brun, A. Harriman, J. Am. Chem. Soc., 1992, 114, 3656.
8. S. Roknic, L. GlavasꢀObrovac, I. Karner, I. Piantanida,
M. Zinic, K. Pavelic, Chemotherapy, 2000, 46, 143.
9. I. Piantanida, B. S. Palm, M. Zinic, H.ꢀJ. Schneider,
J. Chem. Soc., Perkin Trans. 2, 2001, 1808.
12. I. V. Borovlev, O. P. Demidov, Khim. Geterotsikl. Soedin.,
2008, 1613 [Chem. Heterocycl. Compd. (Engl. Transl.), 2008].
13. I. V. Borovlev, O. P. Demidov, A. F. Pozharskii, Khim.
Geterotsikl. Soedin., 2002, 1109 [Chem. Heterocycl. Compd.
(Engl. Transl.), 2002, 968].
14. A. V. Aksenov, A. S. Lyahovnenko, I. V. Aksenova, O. N.
Nadein, Tetrahedron Lett., 2008, 49, 1808.
15. I. V. Borovlev, O. P. Demidov, A. F. Pozharskii, Izv. Akad.
Nauk, Ser. Khim., 2002, 794 [Russ. Chem. Bull., Int. Ed.,
2002, 51, 860].
16. A. F. Pozharskii, V. A. Anisimova, E. B. Tsupak, Prakꢀ
ticheskie raboty po khimii geterotsiklov [Practical Works on
Chemistry of Heterocycles], Rostov State Univ. Publ., Rosꢀ
tovꢀonꢀDon, 1988, 160 pp. (in Russian).
10. I. SteinerꢀBiocic, L. GlavasꢀObrovac, I. Karner, I. Piantaniꢀ
da, M. Zinic, K. Pavelic, J. Pavelic, Anticancer Res., 1996,
16, 3705.
17. F. Uhlig, Angew. Chem., 1954, 66, 435.
11. V. Balzani, A. Credi, S. J. Langford, F. M. Raymo, J. F.
Stoddart, M. Venturi, J. Am. Chem. Soc., 2000, 122, 3542.
Received July 18, 2008;
in revised form December 19, 2008