Reaction of 6(7)-acyl-and 6(7)-formylperimidines with 1,3,5-triazines in poly-phosphoric acid

Article abstract of DOI:10.1007/s10593-008-0121-6

A method has been developed for the synthesis of 1,3,7-triazapyrenes using the reaction of 6(7)-formyl-and 6(7)-benzoylperimidines with 1,3,5-triazines in PPA. Under these conditions, 6(7)-formylperimidine reacts with 2,4,6-trimethyl-1,3,5-triazine to give 6-hydroxy-1,3-diazapyrene.

Full text of DOI:10.1007/s10593-008-0121-6

Chemistry of Heterocyclic Compounds, Vol. 44, No. 7, 2008
REACTION OF 6(7)-ACYL-
AND 6(7)-FORMYLPERIMIDINES
WITH 1,3,5-TRIAZINES IN POLY-
PHOSPHORIC ACID
A. V. Aksenov, I. V. Borovlev, S. V. Pisarenko, and I. V. Aksenova
A method has been developed for the synthesis of 1,3,7-triazapyrenes using the reaction of
6(7)-formyl- and 6(7)-benzoylperimidines with 1,3,5-triazines in PPA. Under these conditions,
6(7)-formylperimidine reacts with 2,4,6-trimethyl-1,3,5-triazine to give 6-hydroxy-1,3-diazapyrene.
Keywords: 6(7)-acylperimidines, 6-hydroxy-1,3-diazapyrene, perimidine, PPA, 1,3,7-triazapyrenes,
1,3,5-triazines, 6(7)-formylperimidine, cyclization.
We have already shown that the 1,3,5-triazine–PPA* system is useful for the acylation and formylation
of perimidines [2] and the synthesis of 1,2,3,7-tetraazapyrenes from 1H-naphtho[1,8-de][1,2,3]triazine
(1,2,3-triazaphenalene) [3]. The present study is a continuation of our investigation of the synthetic scope of this
system. The reaction of this system with 6(7)-acylperimidines 1a-c and 1e and 6(7)-formylperimidine (1d) was
studied in present work.
Since perimidines [2] and 1,2,3-triazaphenalene [3] undergo, in effect, double electrophilic attack by the
system of 1,3,5-triazines 2 in PPA, we might have assumed that perimidines 1 would react analogously. Indeed,
1,3,7-triazapyrenes 3a-d were obtained in 50-65% yield upon heating 1a-d with 1,3,5-triazine (2a) in PPA.
R
R
N
N
N
HN
N
PPA
+
N
N
R1
N
3a–e
O
R1
2a
1a–e
1, 3 a R = H, R1 = Ph, b R = Me, R1 = Ph, c R = R1 = Ph,
d R = R1 = H, e R = H, R1 = Me
_______
* PPA with 86% P2O5 prepared according to Uhlig [1] was used.
__________________________________________________________________________________________
Stavropol State University, Stavropol 355009, Russia; e-mail: k-biochem-org@stavsu.ru. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1080-1084, July, 2008. Original article submitted
June 21, 2007.
868
0009-3122/08/4407-0868©2008 Springer Science+Business Media, Inc.

The reaction with 1e gave a 1:1 mixture of triazapyrenes 3e,d in 61% total yield as indicated by
1H NMR spectroscopy. We were unable to separate the products in light of their similar chromatographic
mobility. The formation of compound 3d may be attributed to the competing deacetylation of acylperimidine 1e
[4] and subsequent reaction of perimidine 4 with triazine 2a.
HN
N
PPA
2a
2a
3d
1e
3e
PPA
PPA
4
The proposed mechanism for the formation of 1,3,7-triazapyrenes 3 is given in the scheme below. Initial
protonation (or phosphorylation) of the carbonyl group oxygen atom in compound 1 gives quinoid structure 5
containing a dienol fragment. This facilitates electrophilic attack of the 1,3,5-triazinium cation at the free peri
position to give 6. Subsequent nucleophilic addition at the carbonyl group and dehydration lead to
intermediate 7, which undergoes the cycloelimination of HCN to give triazapyrenes 3.
R
R
N
N
HN
N
N
N
NH
+
PPA
1a–e
O
HN
R1
N
HO
R1
5a–e
6a–e
N
R
R
+
H
N
HN
N
N
–H2O
3a–e
–2HCN
HO
R1
R1
N
N
N
N
N
N
7a–e
We cannot completely exclude an alternative Diels-Alder reaction mechanism, in which the
1,3,5-triazine acts as a dienophile relative to the diene fragment in the structure 5 and during which the loss of
aromaticity in one ring is compensated by the restoration of aromaticity in another ring.
R
R
N
N
N
N
N
+
3a–e
N
N
– H2O
– 2HCN
2a
H
HO
R1
R1
N
N
HO
5a–e
N
869

The reaction of the aldehyde 1d with 2,4,6-trimethyl-1,3,5-triazine (2b) unexpectedly led to 6-hydroxy-
1,3-diazapyrene (8) instead of the corresponding triazapyrene. Diazapyrene 8 was previously obtained by
another route [5].
Me
N
N
PPA
N
N
1d
+
Me
N
Me
2b
OH
8
This reaction likely involves the crotonic condensation of trimethyltriazine 2b with aldehyde 1d and
subsequent intramolecular acylation. The spiro compound 9 formed after hydrolysis and proton transfer converts
to hydroxydiazapyrene 8.
HN
N
HN
N
HN
N
+
H2O
2b
H
8
1d
Me
N
Me
N
PPA
N
N
N
Me
N
N
+
HN
N
H
Me
Me
Me
9
EXPERIMENTAL
1
The H NMR spectra were taken on a Bruker WP-200 spectrometer at 200 MHz with TMS as the
internal standard. The mass spectra were taken on a MAT-311A spectrometer. The course of the reactions and
purity of the products were monitored by thin-layer chromatography on Silufol UV-254 plates with ethyl acetate
as the eluent.
1,3,7-Triazapyrenes 3a-e (General Method). A mixture of corresponding acylperimidine 1 (1 mmol),
1,3,5-triazine (0.12 g, 1.5 mmol), and PPA (4 g) was stirred for 3 h at 100°C (in the preparation of compound
3e, the reaction was carried out for 2 h at 125°C). The reaction mixture was poured into 30 ml water and brought
to pH ~7-8 by adding ammonium hydroxide. The precipitate was filtered off. In the case of compound 3e, the
reaction mixture after being made alkaline was extracted with three 30-ml ethyl acetate portions. The solvent
was almost entirely evaporated and the crystals precipitated were filtered off.
6-Phenyl-1,3,7-triazapyrene (3a) was obtained in 60% yield (0.168 mg) as light-yellow crystals;
mp 174-176°C (nonane). 1H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.68 (3H, m, 3,4,5-C6H5); 7.91 (2H, br.
d, J = 8.0, 2,6-C6H5); 8.29 (1H, d, J9,10 = 9.5, H-10); 8.33 (1H, d, J4,5 = 9.1, H-4); 8.75 (1H, d, J9,10 = 9.5, H-9);
8.91 (1H, d, J4,5 = 9.1, H-5); 9.86 (1H, s, H-8); 9.89 (1H, s, H-2). Mass spectrum (EI, 70 eV), m/z (Irel, %): 281
[M]+ (100). Found, %: C 81.27; H 3.87; N 14.86. C19H11N3. Calculated, %: C 81.12; H 3.94; N 14.94.
2-Methyl-6-phenyl-1,3,7-triazapyrene (3b) was obtained in 47% yield (0.14 g) as light-orange
1
crystals; mp 246-248°C (nonane). H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 3.19 (3H, s, CH3); 7.63 (3H,
870

m, 3,4,5-C6H5); 7.88 (2H, dd, J = 8.1, J = 1.3, 2,6-C6H5); 8.18 (1H, d, J9,10 = 9.5, H-10); 8.24 (1H, d, J4,5 = 9.2,
H-4); 8.60 (1H, d, J4,5 = 9.2, H-5); 8.76 (1H, d, J9,10 = 9.5, H-9); 9.69 (1H, s, H-8). Found, %: C 81.44; H 4.38;
N 14.18. C20H13N3. Calculated, %: C 81.34; H 4.44; N 14.23.
2,6-Diphenyl-1,3,7-diazapyrene (3c) was obtained in 53% yield (0.189 mg) as yellow crystals;
mp 197-199°C (nonane). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.63 (6H, m, 3,4,5-(2)C6H5,
3,4,5-(6)C6H5); 7.90 (2H, dd, J = 8.1, J = 1.6, 2,6-(6)C6H5); 8.30 (1H, d, J9,10 = 9.5, H-10); 8.35 (1H, d,
J4,5 = 9.2, H-4); 8.63 (1H, d, J5,4 = 9.2, H-5); 8.76 (1H, d, J9,10 = 9.5, H-9); 8.84 (2H, dd, J = 8.1, J = 1.6,
2,6-(2)C6H5); 9.68 (1H, s, H-8). Found, %: C 84.14; H 4.19; N 11.67. C25H15N3. Calculated, %: C 84.01; H 4.23;
N 11.76.
1,3,7-Triazapyrene (3d). The reaction starting with 6(7)-carbaldehyde (1d) gave 0.129 g (63%) 3d. The
1
reaction starting with 6(7)-acetylperimidine (1e) gave 30% 3d as indicated by H NMR spectroscopy. The
1
product was obtained as yellow crystals, mp 240-242°C (octane, subl.) (mp 240-242°C [3]). The H NMR
spectrum for 3d obtained was the same as the spectrum reported in our previous work [3].
6-Methyl-1,3,7-triazapyrene (3e) was obtained from a mixture with 1,3,7-triazapyrene (3d) in
1
1
30% yield as indicated by H NMR spectroscopy. H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 3.25 (3H, s,
CH3); 8.16 (1H, d, J4,5 = 9.1, H-5); 8.22 (1H, d, J9,10 = 9.9, H-9); 8.75 (1H, d, J4,5 = 9.1, H-4); 8.89 (1H, d,
J9,10 = 9.9, H-10); 9.61 (1H, s, H-8); 9.78 (1H, s, H-2).
6-Hydroxy-1,3-diazapyrene (8). A mixture of perimidine-6(7)-carbaldehyde (0.182 g, 1 mmol),
2,4,6-trimethyl-1,3,5-triazine (0.184 g, 1.5 mmol), and PPA (4 g) was stirred rapidly for 2 h at 130°C. The
reaction mixture was poured into water (30 ml) and brought to pH ~7-8 by adding ammonium hydroxide. The
precipitate was filtered off. The mother liquor was heated at reflux until ammonia had been completely
evaporated. The crystals formed upon cooling were filtered off to give 0.105 g (47%) 8 as red-brown crystals,
mp 303-305°C (ethanol) (mp 303-305°C [5]). A mixture with an authentic sample did not give a depressed
melting point. The 1H NMR spectrum was identical to the spectrum reported in previous work [5].
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