New polynitrogen materials based on fused 1,2,4-triazines

Article abstract of DOI:10.1055/s-2006-926242

The synthesis of several novel polynitrogen materials based on fused 1,2,4-triazines is described. A powerful palladium-catalyzed N-heteroarylation strategy followed by a cyclization provides a straightforward one-pot reaction to these tricyclic materials

Full text of DOI:10.1055/s-2006-926242

472
LETTER
New Polynitrogen Materials Based on Fused 1,2,4-Triazines
P
olynitrogen M
t
aterialshel Garnier,a,b Franck Suzenet,a Didier Poullain,b Bruno Lebret,b Gérald Guillaumet*a
a
Institut de Chimie Organique et Analytique (ICOA), UMR-CNRS 6005, FR CNRS 2708, LRC CEA M09, Université d’Orléans,
Rue de Chartres, BP 6759, 45067 Orléans Cedex 2, France
Fax +33(2)38417281; E-mail: gerald.guillaumet@univ-orleans.fr
b
CEA Le Ripault, BP 16, 37260 Monts, France
Received 13 October 2005
These parameters have a fundamental impact on the pres-
sure and the speed of detonations. Therefore, nitro func-
tionalized and polynitrogen tricyclic fused structures were
designed to increase both of these parameters.
Abstract: The synthesis of several novel polynitrogen materials
based on fused 1,2,4-triazines is described. A powerful palladium-
catalyzed N-heteroarylation strategy followed by a cyclization pro-
vides a straightforward one-pot reaction to these tricyclic materials.
Key words: N-arylation reactions, palladium, energetic materials, To access tricyclic structures, the ethyl 5-chloro-3-meth-
1,2,4-triazines
ylsulfanyl-1,2,4-triazine-6-carboxylate (1) seemed to be
an interesting starting material due to its two substituents
in the 5- and 6-position. Indeed the chloride atom could be
displaced in a key amination step and the further cycliza-
tion should occur on an ester moiety (Scheme 1). 1,2,4-
Triazine derivatives are good energetic candidates be-
cause they possess high positive heats of formation and
high crystalline densities. Furthermore, this heterocycle
has received a high degree of attention in the literature due
to its synthetic potential and unique reactivity.2
In 1980, Benichon,3a followed by Huang,3b Warner3c and
Pamukcu,3d described the formation of azapteridines by
reaction of 1 with different amidines under basic condi-
tions. Unfortunately, in our case, by using the 3-amino-5-
nitro-1,2,4-triazole (ANT, an interesting energetic precur-
sor, 2a) and sodium ethoxide in ethanol, no displacement
of the chlorine atom was observed and the starting
material was completely recovered (Scheme 2).
The development of novel heterocyclic materials finds ap-
plications in a wide variety of fields including propellants
and explosives. In the course of our study of new perfor-
mant insensitive energetic molecules, our laboratory was
interested in the synthesis of novel heterocyclic materials
such as polynitrogen tricyclic skeletons to significantly
increase the stability of the final compounds. To our
knowledge, the effects of polynitro functionalization on
mono- or bicyclic rings often gives rise to unstable and
very sensitive compounds.
Our interest in developing tricyclic species was to gener-
ate more stable compounds.1 Indeed, the electron delocal-
ization and the distribution of energetic functions should
be favorable to stabilize the final structures. To generate
very interesting energetic properties, materials have to
satisfy two major criteria: a per volume ratio greater than
1.9 g cm–3 and a high heat of formation (ideally positive).
O2N
2a
NH2
O
O
N
N
N
N
N
N
EtO
N
N
EtO
N
H
R
EtONa, EtOH
r.t., overnight
HN
SMe
O2N
Cl
N
SCH3
N
N
N
N
1
NH
N
H
N
SMe
N
O2N
R = O, NH, ...
Scheme 2 Reactivity of ANT 2a with 1 under basic conditions
O2N
The low level of nucleophilicity displayed by hetero-
aromatic amines is not sufficient to allow substitution on
triazines. In few previous reports on the reactivity of elec-
tron-poor heteroaromatic amines, difficulty was encoun-
tered in preparing N-heteroarylamino-1,2,4-triazines.4
Based on our recent study,5 we speculated that a palladi-
um-catalyzed N-heteroarylation would be the solution to
achieve the key step of the synthetic strategy (Scheme 1).6
A single product was formed and isolated as a yellow oil
as a result of the coupling reaction between the 3-amino-
5-nitro-1,2,4-triazole (2a) with 1 followed by in situ
cyclization. Nevertheless, at this stage, it was not clear
R'
N
N
NH
N
+
N
R' = ester
Cl
SMe
NH2
key amination step
Scheme 1 Access to tricyclic functionalized skeletons
SYNLETT 2006, No. 3, pp 0472–0474
Advanced online publication: 06.02.2006
DOI: 10.1055/s-2006-926242; Art ID: D31505ST
© Georg Thieme Verlag Stuttgart · New York
1
5.
0
2.
2
0
0
6

LETTER
Polynitrogen Materials
473
which of the two possible regioisomers were formed, A or
B (Scheme 3). When the reaction was performed without
palladium catalyst and base, or at room temperature, the
cross-coupling reaction failed.
NH2
O
2b
N
EtO
HN
N
1
cat. Pd(OAc)2, xantphos
K2CO3, dioxane, r.t.
75%
N
SMe
3b
O
O2N
N
N
EtO
N
+
N
Scheme 4 Reactivity of aniline 2b with 1 in Pd-catalyzed
NH2
N
Cl
N
SMe
conditions
H
1
2a
A (Table 1, run 1). This outcome is consistent with the re-
port of Huang,3b reporting that the reaction of compound
1 with ammonia led to substitution of chloride without
reacting with the ester function. It is noteworthy that our
structural assignment is based on the fact that N-alkyl-
ation of triazole is described to occur at N(1) rather than
N(4).8
cat. Pd(OAc)2, xantphos
K2CO3, dioxane, reflux
71%
O
O
N
N
N
N
N
N
HN
N
O2N
or
N
H
A
N
SMe
N
N
SMe
N
N
Table 1 N-Arylations9 with Various Heteroarylamines 2a,c–h
B
O2N
Run
Amine
Producta
Yield
(%)b,c
Scheme 3 Two possible regioisomers A or B
H
N
O
N
Owing to the lack of hydrogens on the final compound (A
or B) and our inability in accessing suitable single crys-
tals, we used N NMR analysis to confirm the structure
NH2
N
N
N
N
N
O
1
2a
2c
2d
2e
2f
3a 71
N
15
N
O2N
O2N
N
H
S
of this novel polynitrogen compound. Eight nitrogen en-
vironments were observed including the characteristic
signals for NO2 and NH at d = 12 ppm and d = –258 ppm,
H
N
NH2
N
N
N
N
1
respectively.7 Both H NMR and 13C NMR spectra con-
2
3
4
5
3c 65
3d 62
3e 67
3f 64
N
N
firmed the disappearance of the ethyl chain. Moreover,
mass spectrometry revealed no presence of a chloro
group. The presence of the amino and carbonyl function
was confirmed by IR analysis. Therefore, in an attempt to
determine the exact structure of the final product
(Scheme 3) we wondered if (i) the substitution of the chlo-
rine atom was carried out by the NH or NH2 of the azole
moiety, and (ii) if the first step is the amide formation or
N-arylation.
According to our previous report,5 in amino–azahetero-
cycle bearing at least two nucleophilic nitrogens, the pri-
mary amine was the most reactive. Consequently, we
assumed that in the present case the exocyclic amine re-
acts first. However, we were reluctant to make a definitive
structural assignment without being sure that the coupling
reaction constituted the first step of the cyclization. For
this purpose, we compared the reactivity of the ester and
chloro functions of compound 1 using a substrate bearing
only one nucleophilic amine. As a model, aniline 2b was
reacted with compound 1. The reaction was found to take
place at position 5 of the triazine ring to give compound
3b in 75% yield (Scheme 4). This result shows that the
palladium-catalyzed N-arylation reaction occurs before
the addition–elimination reaction with the ester function.
N
H
N
S
H
O
N
NH2
N
N
N
N
N
H
N
S
S
O
H
N
NH2
N
N
N
N
N
N
N
N
H
N
O
H
NC
N
NC
NH2
N
N
N
N
NC
NC
N
N
H
N
S
H
N
O
NH2
N
N
N
N
N
N
6
7
2g
2h
3g 68
3h 59
NO2
N
H
S
O2N
O
N
N
N
N
N
NH2
N
N
N
S
Therefore, this ‘one-pot’ cyclization mechanism occurs
first by the N-arylation reaction followed by the cycliza-
tion with the ester moiety, leading to the only regioisomer
a Yield of pure, isolated compound.
b The remaining material was constituted of degradation compounds.
Synlett 2006, No. 3, 472–474 © Thieme Stuttgart · New York

474
E. Garnier et al.
LETTER
These first optimized conditions5 were used for a compar-
ative study with different heteroarylamines (Table 1).9
Various five-membered heterocycles were reacted with
triazine 1 and after ‘one-pot’ cyclization, the correspond-
ing tricyclic fused heterocycles were isolated in 62% to
71% isolated yield (Table 1, runs 1–6). Six-membered
ring amines also react. For example, 2-aminopyrimidine
(2h) was converted to compound 3h in 59% yield
(Table 1, run 7).
(4) (a) Jonckers, T. H. M.; Maes, B. U. W.; Lemière, G. L. F.;
Dommisse, R. Tetrahedron 2001, 57, 7027. (b) Košmrlj, J.;
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2000, 2, 293. (d) Schoffers, E.; Olsen, P. D.; Means, J. C.
Org. Lett. 2001, 3, 4221. (e) Yin, J.; Zhao, M. M.; Huffman,
M. A.; McNamara, J. M. Org. Lett. 2002, 4, 3481.
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D.; Lebret, B.; Guillaumet, G. J. Org. Chem. 2004, 69, 7809.
(6) For reviews about metal-catalyzed C–N bond formation,
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(7) For chemical shift assignment, see: Martin, M. L.;
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A. R.; Rees, C. W.; Scriven, E. F. W., Eds.; Pergamon Press:
Oxford UK, 1996, 127.
We have demonstrated that palladium-catalyzed N-het-
eroarylation conditions can be used with ethyl 5-chloro-3-
methylsulfanyl-1,2,4-triazine-6-carboxylate (1) and
various electron-poor amines 2a–h. Our optimized cou-
pling conditions were successfully applied to the ‘one-
pot’ synthesis of compounds 3a,c–h, in good yields.
Current efforts are directed towards the reactivity of the
methylsulfanyl group in order to increase the energetic
properties of the final products. These studies will be
communicated in due course.
References and Notes
(9) Typical Procedure for the Pd-Catalyzed N-Arylation
Cyclization.
(1) (a) Millar, R. W.; Philbin, S. P.; Claridge, R. P.; Hamid, J.
Propellants, Explos., Pyrotech. 2004, 81. (b) Sikder, A. K.;
Sikder, N. J. Hazard. Mater. 2004, A112, 1. (c) Singh, G.;
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A three-necked flask was flushed with N2 and charged with
xantphos (20 mol%) and dry dioxane (5 mL). After
degassing, Pd(OAc)2 (10 mol%) was added and the mixture
was stirred under N2 for 10 min. In another three-necked
round-bottom flask, compound 1 (0.100 g, 1.0 equiv),
heteroarylamine (1.2 equiv) and K2CO3 (20 equiv) were
poured into dry dioxane (7 mL). Then, the Pd(OAc)2/
xantphos solution was added via cannula. The resulting
mixture was subsequently heated to reflux and vigorously
stirred until 1 has disappeared. After cooling down, the solid
material was filtered off and washed with CH2Cl2 (20 mL)
and MeOH (20 mL). The solvent was evaporated and the
resulting crude product was purified by flash column
chromatography using CH2Cl2–MeOH (99:1 v/v) as eluent.
Characterization of Compounds 3a and 3b.
(2) For C–C bond formation, see: (a) Alphonse, F.-A.; Suzenet,
F.; Keromnes, A.; Lebret, B.; Guillaumet, G. Synlett 2002,
447. (b) Alphonse, F.-A.; Suzenet, F.; Keromnes, A.; Lebret,
B.; Guillaumet, G. Org. Lett. 2003, 5, 803. (c) Alphonse,
F.-A.; Suzenet, F.; Keromnes, A.; Lebret, B.; Guillaumet, G.
Synthesis 2004, 2893. (d) For general chemistry, see:
Neunhoffer, H. Comprehensive Chemistry II, Vol. 6;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. W., Eds.;
Pergamon Press: Oxford UK, 1996, 507. For inverse-
electron-demand Diels–Alder reaction, see: (e) Lipinska, T.
Tetrahedron Lett. 2002, 43, 9565. (f) Lahue, B.; Wan, Z.-
K.; Snyder, J. K. J. Org. Chem. 2003, 68, 4345. (g) Lahue,
B. R.; Lo, S.-M.; Wan, Z.-K.; Woo, G. H. C.; Snyder, J. K.
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2003, 2096. (i) Bilbao, E. R.; Alvarado, M.; Masguer, C. F.;
Ravina, E. Tetrahedron Lett. 2002, 43, 3551 . For fused
1,2,4-triazine derivatives, see: (j) Garnier, E.; Guillard, J.;
Pasquinet, E.; Suzenet, F.; Poullain, D.; Jarry, C.; Léger, J.-
M.; Lebret, B.; Guillaumet, G. Org. Lett. 2003, 5, 4595.
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Compound 3a: 1H NMR (200 MHz, DMSO): d = 2.10 (s, 3
H, CH3), 11.97 (br s, 1 H, NH) ppm. 13C NMR (50 MHz,
DMSO): d = 13.1 (CH3), 144.8 (C10a), 153.7 (C5a), 154.1
(C10), 154.6 (C4a), 165.5 (C7), 178.1 (C3) ppm. 15N NMR (30
MHz, DMSO): d = –296, –258 (NH), –133, –154, –54, –49,
5, 12 (NO2) ppm. IR: n = 3223, 2975, 1652, 1521, 1352,
1023 cm–1. MS: m/z = 281 [M + 1]. Anal. Calcd for
C7H4N8O3S: C, 30.00; H, 1.44; N, 39.99. Found: C, 30.11;
H, 1.48; N, 40.05.
Compound 3b: 1H NMR (200 MHz, DMSO): d = 1.30 (t,
J = 8.1 Hz, 3 H, CH3), 2.37 (s, 3 H, SCH3), 4.14 (q, J = 8.1
Hz, 2 H, CH2), 7.03 (dd, J2¢,4¢ = 1.1 Hz, J3¢,4¢ = 7.4 Hz, 1 H,
H4¢), 7.43 (dd, J2¢,3¢ = 7.9 Hz, J3¢,4¢ = 7.4 Hz, 2 H, H3¢ and H5¢),
7.93 (dd, J2¢,4¢ = 1.1 Hz, J2¢,3¢ = 7.9 Hz, 2 H, H2¢ and H6¢),
11.43 (br s, 1 H, NH) ppm. 13C NMR (50 MHz, DMSO): d =
12.1 (CH3), 14.07 (CH3), 62.0 (CH2), 122.9 (C4¢), 123.5 (C2¢
and C6¢), 126.6 (C3¢ and C5¢), 140.5 (C6), 149.4 (C1¢), 155.6
(C5), 163.8 (C=O), 188.1 (C3) ppm. IR: n = 3188, 2932,
1726, 1663 cm–1. MS: m/z = 291 [M + 1]; mp 85–87 °C.
Anal. Calcd for C13H14N4O2S: C, 53.78; H, 4.86; N, 19.30.
Found: C, 54.01; H, 4.54; N, 19.12.
Tetrahedron Lett. 1987, 28, 1977. (d) Piazza, G. A.;
Pamukcu, R. Am. Pat. Appl. US6060477, 2000; Chem.
Abstr. 2000, 132, 321870.
Synlett 2006, No. 3, 472–474 © Thieme Stuttgart · New York