Synthesis of 1,3-diazapyrenes and 1,3,7-triazapyrenes by the reaction of 1,8-naphthalenediamine with triazine in the presence of carbonyl compounds or benzonitrile in polyphosphoric acid

Article abstract of DOI:10.1007/s10593-009-0192-z

A novel three-component synthesis has been developed for 1,3-diazapyrenes based on the reaction of 1,8-naphthalenediamine with triazine and carbonyl compounds in polyphosphoric acid (PPA). The use of benzonitrile in place of the carbonyl compounds in this

Full text of DOI:10.1007/s10593-009-0192-z

Chemistry of Heterocyclic Compounds, Vol. 44, No. 11, 2008
SYNTHESIS OF 1,3-DIAZAPYRENES
AND 1,3,7-TRIAZAPYRENES BY THE REACTION
OF 1,8-NAPHTHALENEDIAMINE WITH TRIAZINE
IN THE PRESENCE OF CARBONYL COMPOUNDS
OR BENZONITRILE IN POLYPHOSPHORIC ACID*
A. V. Aksenov, I. V. Aksenova, A. S. Lyakhovnenko, and N. A. Aksenov
A novel three-component synthesis has been developed for 1,3-diazapyrenes based on the reaction of
1,8-naphthalenediamine with triazine and carbonyl compounds in polyphosphoric acid (PPA). The use
of benzonitrile in place of the carbonyl compounds in this reaction gives 6-phenyl-1,3,7-triazapyrenes.
Keywords: 1,3-diazapyrenes, 1,8-naphthalenediamine, perimidines, PPA, 1,3,7-triazapyrenes,
1,3,5-triazine, annelation.
We have previously [1, 2] developed a method for the acylation (formylation) of perimidines based on
their reaction with 1,3,5-triazines in PPA*2.
In the case of synthesis of 1,2,3,7-tetraazapyrenes using this system of reagents the peri annelation of a
pyridine ring was shown to be possible [4]. It was of interest to broaden this synthetic potential by the addition
of an further reagent. In this report we discuss the reaction of 1,8-naphthalenediamine with triazine 2 in PPA in
the presence of carbonyl compounds and benzonitrile.
The reaction of diamine 1 with triazine 2 gives the perimidine 3a [5] which, as we have recently shown
[1, 2], gives the perimidine-6(7)-carbaldehyde (5) after reaction with compound 2 in PPA and then treatment of
the reaction mixture with water. The compound 4a was postulated as intermediate.
NH
NH
N
N
NH
N
NH2
NH2
N
2
PPA
H2O
+
PPA
N
N
3a
2
1
O
N
NH
5
N
4a
_______
* Dedicated to one of the best Russian chemists A. F. Pozharskii on his 70th jubilee.
*2 PPA with an 86% content of P2O5 was prepared by the method [3]
__________________________________________________________________________________________
Stavropol State University, Stavropol 355009, Russia; e-mail: k-biochem-org@stavsu.ru. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1694-1698, November, 2008. Original article
submitted November 6, 2007.
0009-3122/08/4411-1379©2008 Springer Science+Business Media, Inc.
1379

We have suggested that the first two stages can be combined. In fact, the reaction of diamine 1 with
triazine 2 in the ratio 1:3 gives compound 5 after hydrolysis of the reaction mixture in near quantitative yield.
1) 2/PPA
1
5
2) H2O
We have further proposed that opening of the dihydrotriazine ring in the intermediate 4a can be brought
about not only by water but also by other nucleophilic reagents, e.g. the carbonyl compounds 6. Moreover, as a
result of the presence of an electrophilic center (the carbonyl group) in the intermediate material 7 a cyclization
can occur resulting in formation of the 1,3-diazapyrenes 8.
R
NH
N
N
N
X
O
6a–c
+
H
4a
– HN=CHNH2
– HCN
R
R
O
X
X
7a–c
6–8 a R = Ph, X = H, b R = Me, X = COOEt, c R = Me, X = COMe
8a–c
In fact, the reaction of diamine 1 with triazine 2 and the carbonyl compounds 6a-c (molar ratio 1:3:3) in
PPA gives the 1,3-diazapyrenes in 57-68% yields.
PPA
8a–c
6a–c
1
2
+
+
60–70°C
It is known that the reaction of diamine 1 with benzonitrile leads to formation of the 2,6,8-triphenyl-
1,3,7-triazapyrene [6] hence it can be expected that compound 4a will react with benzonitrile to give the
6-phenyl-1,3,7-triazapyrene 9a.
R
R
R
N
N
NH
NH
N
N
– H2NCONH2
– HCN
PhCN
PPA
NH
Ph
HN
N
HN
N
Ph
N
9a–c
N
N
4a–c
4, 9 a R = H, b R = Me, c R = Ph
The yield of compound 9a in the three component reaction of compounds 1, 2, and benzonitrile in PPA
is 72%.
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2, PhCN
1
9a
PPA

Bearing in mind that the intermediate compounds 4a-c can be prepared from the perimidines 3a-c we
also developed a method for the synthesis of triazapyrenes 9a-c via a three component reaction of compounds
3a-c, 2 and benzonitrile in PPA in 71-75% yield.
R
N
NH
2, PhCN
9a–c
PPA
3a–c
3, 9 a R = H, b R = Me, c R = Ph
For the reaction given above an alternative mechanism can be proposed with a stage of annelation of the
ring which includes formation of the intermediate 10 via opening of the dihydrotriazine ring in compound 4 and
a subsequent Diels-Alder reaction to form the intermediates 11 and 12.
N
N
– HN=CHNH2
– HCN
9a–c
H
N
N
PhCN
HN
N
Ph
N
N
NH
N
4a
11
R
H
X
HN
O
N
NH
– HN=CHNH2
– HCN, – H2O
8a–c
10
H
R
NH
HN
OH
X
N
12
EXPERIMENTAL
1H NMR spectra were recorded on a Bruker WP-200 (200 MHz) instrument using CDCl3 (compounds
8a-c, 9b,c) or DMSO-d6 (compound 9a) with TMS as internal standard and mass spectra were taken on a
MAT-311A instrument. Monitoring of the course of the reaction and the purity of the synthesized compounds
was carried out on Silufol UV-254 plates using ethyl acetate solvent. Column chromatography was carried out
on L 40/100 silica gel using ethyl acetate eluent.
Perimidine-6(7)-carbaldehyde (5). A mixture of 1,8-naphthalenediamine (0.154 g, 1 mmol) and
1,3,5-triazine (0.243 g, 3 mmol) in PPA (3-4 g) was stirred vigorously for 9 h at 60-70ºC, the reaction mixture
was poured into water (30 ml), basified by ammonia solution to pH ~ 7-8, and the crystals formed after cooling
were extracted with ethyl acetate (3×50 ml). The solvent was evaporated. Yield 91%; mp 212-214ºC (acetic
acid); mp 212-214ºC [7]. A sample mixed with a known sample did not give a depression of melting point. The
1H NMR spectrum was identical to that given in [7].
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Synthesis of the 1,3-Diazapyrenes 8a-c (General Method). A mixture of 1,8-naphthalenediamine
(0.154 g, 1 mmol), 1,3,5-triazine (0.243 g, 3 mmol), and the corresponding carbonyl compound (3 mmol) in
PPA (3-4 g) was stirred vigorously for 9h at 60-70ºC. The reaction mixture was poured into water (30 ml),
basified using ammonia solution to pH ~ 7-8, and the crystals or oil formed after cooling were extracted with
ethyl acetate (3 x 50 ml). Solvent was evaporated and the residue was chromatographed.
6-Phenyl-1,3-diazapyrene (8a). Yield 0.16 g (57%); mp 193-195ºC (ethyl acetate). 1H NMR spectrum,
δ, ppm (J, Hz): 7.59-7.64 (5H, m, C6H5); 8.15 (1H, d, J7,8 = 7.72, H-7); 8.32 (1H, d, J4,5 = 9.4, H-5); 8.41 (1H, d,
J7,8 = 7.7, H-8); 8.48 (1H, d, J9,10 = 9.4, H-9); 8.76 (1H, d, J4,5 = 9.4, H-4); 8.98 (1H, d, J9,10 = 9.4, H-10); 9.76
(1H, s, H-2). Found, %: C 85.82; H 4.25; N 8.93. C20H12N2. Calculated, %: C 85.69; H 4.32; N 9.99.
Ethyl 6-Methyl-1,3-diazapyrene-7-carboxylate (8b). Yield 0.197 g (68%); mp 153-154ºC (ethyl
1
acetate). H NMR spectrum, δ, ppm (J, Hz): 1.52 (3H, t, J = 6.8, CH3CH2); 3.26 (3H, s, CH3); 4.55 (2H, q,
J = 6.9, CH3CH2); 8.22 (1H, d, J9,10 = 9.5, H-9); 8.31 (1H, d, J4,5 = 9.5, H-5); 8.55 (1H, d, J9,10 = 9.5, H-10); 8.85
(1H, s, H-8); 8.93 (1H, d, J4,5 = 9.5, H-4); 9.80 (1H, s, H-2). Found, %: C 74.58; H 4.81; N 9.58. C18H14N2O2.
Calculated, %: C 74.47; H 4.86; N 9.65.
7-Acetyl-6-methyl-1,3-diazapyrene (8c). Yield 0.266 g (64%); mp 161-163ºC (ethyl acetate). 1H NMR
spectrum, δ, ppm (J, Hz): 2.86 (3H, s, COCH3); 3.14 (3H, s, CH3); 8.23 (1H, d, J9,10 = 9.5, H-9); 8.31 (1H, d,
J4,5 = 9.5, H-5); 8.54 (1H, d, J9,10 = 9.5, H-10); 8.55 (1H, s, H-8); 8.90 (1H, d, J4,5 = 9.5; H-4); 9.83 (1H, s, H-2).
Found, %: C 78.58; H 4.59; N 10.71. C17H12N2O. Calculated, %: C 78.44; H 4.65; N 10.76.
Synthesis of 6-Phenyl-1,3,7-triazapyrene (9a) from 1,8-Naphthalenediamine. A mixture of
1,8-naphthalenediamine (0.154 g, 1 mmol), 1,3,5-triazine (0.243 g, 3 mmol), and benzonitrile (0.515 g, 5 mmol)
in PPA (3-4 g) was vigorously stirred for 8 h at 60-70ºC. The reaction mixture was poured into water (30 ml),
basified with ammonia solution to pH ~ 7-8, and the crystals formed after cooling were extracted with ethyl
acetate (3×50 ml). Solvent was evaporated and the residue was chromatographed.
Synthesis of 2-R-6-Phenyl-1,3,7-triazapyrenes 9a-c from Perimidines 3a-c (General Method). A
mixture of the corresponding perimidine (1 mmol), 1,3,5-triazine (0.243 g, 3 mmol), and benzonitrile (0.515 g,
5 mmol) in PPA (3-4 g) was vigorously stirred for 8 h at 60-7-ºC. The reaction mixture was poured into water
(30 ml), basified with aqueous ammonia solution to pH ~ 7-8, and the crystals or oil formed after cooling were
extracted with ethyl acetate (3×50 ml). Solvent was evaporated and the residue was chromatographed.
6-Phenyl-1,3,7-triazapyrene (9a). Yield from 1,8-naphthalenediamine 0.2 g (72%), from the
1
perimidine 0.211 g (75%); mp 174-176ºC (nonane). H NMR spectrum, 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
(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.
1
2-Methyl-6-phenyl-1,3,7-triazapyrene (9b). Yield 0.21 g (71%); mp 246-248ºC (nonane). H NMR
spectrum, δ, ppm (J, Hz): 3.19 (3H, s, CH3); 7.63 (3H, m, 3,4,5-C6H5); 7.88 (2H, dd, J = 8.1, J = 1.3, 2,6-C6H5); 8.2
(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.
1
2,6-Diphenyl-1,3,7-triazapyrene (9c). Yield 0.264 g (74%); mp 197-199ºC (nonane). H NMR
spectrum, 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 (2H, d, J4,5 = 9.2, H-4); 8.63 (1H, d, J4,5 = 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.
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