New approaches to synthesis of tris[1,2,4]triazolo[1,3,5]triazines

Article abstract of DOI:10.1007/s11172-005-0310-8

Thermal cyclization of 3-R-5-chloro-1,2,4-triazoles (R = Cl, Ph) afforded 2,6,10-tri-R- tris[1,2,4]triazolo[1,5-a:1′,5′c:1″,5″-e] [1,3,5]triazines 5 (R = Ph) and 7 (R = Cl). These compounds are first representatives of this class of heterocycles, whose st

Full text of DOI:10.1007/s11172-005-0310-8

Russian Chemical Bulletin, International Edition, Vol. 54, No. 3, pp. 719—725, March, 2005
719
New approaches to synthesis of tris[1,2,4]triazolo[1,3,5]triazines
ꢀ
V. A. Tartakovsky, A. E. Frumkin, A. M. Churakov, and Yu. A. Strelenko
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: tva@ ioc.ac.ru
Thermal cyclization of 3ꢀRꢀ5ꢀchloroꢀ1,2,4ꢀtriazoles (R = Cl, Ph) afforded 2,6,10ꢀtriꢀRꢀ
tris[1,2,4]triazolo[1,5ꢀa:1´,5´ꢀc:1″,5″ꢀe][1,3,5]triazines 5 (R = Ph) and 7 (R = Cl). These
compounds are first representatives of this class of heterocycles, whose structures were unamꢀ
biguously established. Treatment of these compounds with nucleophiles (H2O/NaOH, NH3)
results in the triazine ring opening to give compounds consisting of three 1,2,4ꢀtriazole rings
linked in a chain. For example, treatment of cyclic compound 5 with aqueous alkali affords
3ꢀphenylꢀ1ꢀ{3ꢀphenylꢀ1ꢀ(3ꢀphenylꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀyl)ꢀ1,2,4ꢀtriazolꢀ5ꢀyl}ꢀ1Hꢀ1,2,4ꢀ
triazolꢀ5ꢀone. Treatment of 3,7,11ꢀtriphenyltris[1,2,4]triazolo[4,3ꢀa:4´,3´ꢀc:4″,3″ꢀe][1,3,5]triꢀ
azine (2) with HCl/SbCl5 leads to the triazine ring opening giving rise to 5ꢀ(3ꢀchloroꢀ
5ꢀphenylꢀ1,2,4ꢀtriazolꢀ4ꢀyl)ꢀ3ꢀphenylꢀ4ꢀ(5ꢀphenylꢀ1Hꢀ1,2,4ꢀtriazolꢀ3ꢀyl)ꢀ1,2,4ꢀtriꢀ
azole. Thermal cyclization of the latter produces 3,7,10ꢀtriphenyltris[1,2,4]triazoꢀ
lo[1,5ꢀa:4´,3´ꢀc:4″,3″ꢀe][1,3,5]triazine (13). Thermolysis of both cyclic compound 2 and cyꢀ
clic compound 13 is accompanied by the Dimroth rearrangement to yield 3,6,10ꢀtriphenylꢀ
tris[1,2,4]triazolo[1,5ꢀa:1´,5´ꢀc:4″,3″ꢀe][1,3,5]triazine (14). Compounds 13 and 14 are the
first representatives of cyclic compounds with this skeleton. 13C NMR spectroscopy allows the
determination of the isomer type in a series of tris[1,2,4]triazolo[1,3,5]triazines.
Key words: fused heterocycles, nitrogen heterocycles, 1,2,4ꢀtriazoles, 1,3,5ꢀtriazines,
tris[1,2,4]triazolo[1,3,5]triazine, pyrolysis, Dimroth rearrangement, synthetic methods.
Scheme 1
The 1,2,4ꢀtriazole ring can be fused to the 1,3,5ꢀtriꢀ
azine ring in two ways to give the structure А or B. Let us
denote the 1,2,4ꢀtriazole ring involved in the strucꢀ
tures А and B as the X ring and Y ring, respectively.
Tris[1,2,4]triazolo[1,3,5]triazine in which the triazine ring
is fused to three triazole rings is designated as TTT.
In
the
early
20th
century,
the
first
tris[1,2,4]triazolo[1,3,5]triazine was prepared by heating
3,5ꢀdiaminoꢀ1,2,4ꢀtriazole (guanazole).1 The authors of
the cited paper1 assigned structure Y3ꢀTTT 1a to this
compound (Scheme 1) and called it pyroguanazole. More
recently, structure X3ꢀTTT 1b was proposed2 for this comꢀ
pound based on its chemical behavior. However, the asꢀ
signment is not conclusive and, in essence, the choice
between structures 1а and 1b was not made.
cyanuric chloride with 1ꢀphenyltetrazole (Scheme 2). The
reaction mechanism involving the intermediate formaꢀ
tion of nitrile imine C unambiguously determines the X3
structure of compound 2, and the relatively low therꢀ
molysis temperature excludes the possibility of a skeletal
rearrangement (for details, see below).
Triphenylꢀsubstituted compound 2 with the structure
X3ꢀTTT was prepared by Huisgen et al.3 by the reaction of
To our knowledge, the above compounds are the only
known tris[1,2,4]triazolo[1,3,5]triazines.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 706—712, March, 2005.
1066ꢀ5285/05/5403ꢀ0719 © 2005 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 3, March, 2005
Tartakovsky et al.
Scheme 2
they are potential components of materials with high therꢀ
mal stability.
Synthesis of Y3ꢀTTT
By analogy with the Hofmann—Erhart method,1 we
attempted to synthesize triphenylꢀsubstituted TTT by pyꢀ
rolysis of 5ꢀaminoꢀ3ꢀphenylꢀ1,2,4ꢀtriazole (3а). However,
this attempt was unsuccessful. Heating of 5ꢀmethylthioꢀ
3ꢀphenylꢀ1,2,4ꢀtriazole (3b) also did not give the desired
result. Pyrolysis of 5ꢀchloroꢀ3ꢀphenylꢀ1,2,4ꢀtriazole (4)
afforded compound 5 with the Y3 structure.*
The best results were obtained upon heating of triazole
4 without a solvent at 230—270 °C (the yield of 5 was 46%).
Heating in sulfolane at the same temperature afforded
compound 5 in lower yield (12%). Under thermolysis
conditions, TTT 5 is stable. Compound 5 begins to deꢀ
compose during melting only at about 400 °C.
For thermolysis of 5ꢀchloroꢀ3ꢀphenylꢀ1,2,4ꢀtriazole
4 to form TTT with the Y3 structure, it is necessary that
the N(1) atom of triazole be the attacking nucleophile
both in the first and second steps of the reaction, and the
N(1) atom of the intermediate linear trimer be the attackꢀ
ing nucleophile in the third step (Scheme 4).
i. Toluene, reflux.
It should be noted that the mechanism involving the
initial formation of X3ꢀTTT 2 followed by its rearrangeꢀ
The aim of the present study was to develop new proꢀ
cedures for the synthesis of tris[1,2,4]triazolo[1,3,5]triꢀ
azines, which differ in the mutual arrangement of the
triazole rings. This class of compounds is of interest from
the standpoint of their biological activity and also because
* Examples of thermal trimerization of imidazoles and pyrazoles
containing the chlorine atom4,5 or the methylthio group6 were
described in the literature.
Scheme 3
3: X = NH2 (a), SMe (b)
Scheme 4

Synthesis of tris[1,2,4]triazolo[1,3,5]triazines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 3, March, 2005
721
Table 1. 13C NMR spectroscopic data for TTT (DMSOꢀd6)
Comꢀ
pound
δ (J/Hz)
C(1)
C(2)
C(2)
Ph
X ring
Y ring
ipso
ortho, meta
para
2
5
141.9
145.5
149.2
3J = 4.5
—
—
124.6
128.5, 129.8
131.4
162.8
3J = 4.0
157.4
128.2
126.8, 129.0
131.1
7
13
145.6
142.3, 142.7,
143.8
143.1, 144.3,
144.9
—
—
—
—
148.8, 149.4
161.9
124.3, 124.7, 128.2
126.7, 128.5, 128.6,
129.3, 129.9, 130.1
126.6, 126.8, 128.4,
129.3, 129.9
131.4, 131.5,
131.7
131.3, 131.4,
131.5
14
148.7
161.9,
162.8
124.4, 128.1, 128.3
* Two superimposed signals.
ment into Y3ꢀTTT 5 can be excluded because this rearꢀ
rangement (as demonstrated below) occurs at higher temꢀ
perature.
In addition to TTT 7, thermolysis in the absence of
the solvent afforded two groups of products, which were
isolated by chromatography. The 13C NMR spectra demꢀ
onstrate that the first group consists of four main comꢀ
pounds. The spectrum of each compound shows two sigꢀ
nals for carbon atoms at δ 145—146 and 154—158 (all
signals of the mixture of four compounds, δ: 145.2, 145.5,
145.8, 146.0, 154.7, 156.0, 157.5, 157.6). These chemical
shifts are similar to those of Y3ꢀTTT 7 (Table 1). We
believe that these compounds are macrocyclic analogs of
trimer 7, which is confirmed by the fact that their mass
spectra have signals of both the tetramer (m/z: 404 [M]+)
and the pentamer (m/z: 470 [M – Cl]+). The second
group of products consists, presumably, of trimeric cyclic
compounds 7, in which one, two, or three chlorine atoms
are replaced by the 3,5ꢀdichloroꢀ1,2,4ꢀtriazole fragment.
This is evidenced by the fact that the mass spectrum of
these compounds has peaks at m/z: 404 [M]+, 505 [M]+,
606 [M]+.* These compounds could most likely be formed
directly by cyclization of the corresponding linear chains
rather than by the replacement of the chlorine atoms in
cyclic compound 7.
Thermal cyclization appeared to be suitable also for
the synthesis of trichloroꢀsubstituted Y3ꢀTTT 7. This comꢀ
pound was prepared in 17% yield by heating 3,5ꢀdichloroꢀ
1,2,4ꢀtriazole 6 in the absence of a solvent at 240—270 °C.
Heating in sulfolane led to an increase in the yield to 20%.
The latter procedure is preferable also because it makes
isolation of the product easier. Compound 7 crystallizes
in pure form upon cooling of the reaction mixture to
room temperature. Trichloroꢀsubstituted TTT 7, like
triphenylꢀsubstituted TTT 5, is thermally stable (m.p.
311—313 °C, without decomposition).
Scheme 5
Triazine ring opening in TTT
The chemical properties of triphenylꢀsubstituted
X3ꢀTTT 2 differ substantially from those of Y3ꢀTTT 5.
i. 240—270 °C, sulfolane (20%).
* Only signals with the 35Cl isotope are given.

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Tartakovsky et al.
Scheme 6
Reagents, conditions, and yields of products: i. HCl/SbCl5, dioxane, reflux, 83% yield; ii. H2O/NaOH or H2O/HCO2H, yield >90%.
Scheme 7
The triazine ring opening in Y3ꢀTTT 7 occurs also in the
presence of ammonia to form compound 12.
To our knowledge, compounds consisting of three
triazole rings linked in a chain (compounds 8—12) have
not been described earlier.
Synthesis of X2YꢀTTT and XY2ꢀTTT
To prepare phenylꢀsubstituted X2YꢀTTT 13 containꢀ
ing three triazole rings (two X rings and one Y ring), we
attempted to perform cyclization of compounds 8 and 9.
Triazolone 8 appeared to be an inert compound. The
addition of a concentrated alkali, refluxing in POCl3, or
heating at 350 °C did not lead to cyclization of 8. By
contrast, chloro derivative 9 undergoes smooth cyclization
at 240 °C to form compound X2YꢀTTT 13 (Scheme 9).
An attempt to prepare this compound by the rearrangeꢀ
ment of X3ꢀTTT 2 failed. The latter compound remained
unchanged upon prolonged storage at 240 °C.
Heating of X2YꢀTTT 13 at higher temperature (350 °C)
afforded XY2ꢀTTT 14 containing two triazole Y rings.
This compound was also prepared directly from X3ꢀTTT
2 by heating at 350 °C. Under these conditions, the reacꢀ
tion produced also trace amounts of Y3ꢀTTT 5 (TLC
data), in which all three triazole rings are rearranged.
The transformation of the triazole X ring into the Y ring
can be assigned to the Dimroth rearrangement.7 Howꢀ
ever, the mechanism of the rearrangement involving the
i. H2O/NaOH, 77% yield
Compound 2 is more reactive and is relatively easily hydroꢀ
lyzed in both alkaline and acidic media, resulting in the
triazine ring opening to form triazolone 8 (Scheme 6). An
interesting fact is that the triazine ring of X3ꢀTTT 2 is
opened with HCl in the presence of SbCl5 as the catalyst
to form chloroꢀsubstituted compound 9. It should be noted
that an attempt to prepare this compound by treatment of
triazolone 8 with phosphorus(V) oxychloride failed.
Compound 5 is stable to acidic hydrolysis and to the
action of HCl/SbCl5 and gives triazolone 10 only in the
presence of an alkali.
Compound 7, like compound 5, is stable to acidic
hydrolysis and forms triazolone 11 only in the presence of
an alkali, the reaction proceeding under milder condiꢀ
tions than those of triphenylꢀsubstituted TTTs 2 and 5.
Scheme 8
Reagents, conditions, and yields of products: i. NH3, dioxane, 83% yield; ii. H2O/NaOH, 61% yield.

Synthesis of tris[1,2,4]triazolo[1,3,5]triazines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 3, March, 2005
723
Scheme 9
Reagents, conditions, and yields of products: a. HCl/SbCl5, dioxane; b. 240 °C, 71% yield; c. 350 °C, 80% yield; d. 350 °C, yield >95% 14,
trace amounts of 5.
cleavage of the bond between two heterocycles has not, to
our knowledge, been described in the literature. The therꢀ
mal Dimroth rearrangement for structures similar to those
under study generally occurs at temperatures below 250 °C.
The proposed mechanism involves the ionic cleavage of
the C—N bond to form intermediate 15, in which both
the cationic and anionic parts of the zwitterion are stabiꢀ
lized (Scheme 10).
positive charge cannot be well distributed. Taking into
account also the high reaction temperature, the radical
mechanism of the rearrangement involving the intermeꢀ
diate formation of biradical 17 cannot be ruled out as well.
Structure of TTT
13C NMR spectroscopy is the most convenient method
for establishing the structures of TTT systems. We carried
out a comparative study of X3ꢀTTT 2 and Y3ꢀTTT 5. The
unambiguous assignment of the signals of these comꢀ
pounds was made based on the 13C NMR spectra meaꢀ
sured without proton decoupling (see Table 1). The signal
for C(2) of the X triazole ring is observed at much higher
field compared to the signal for C(2) of the Y triazole ring
(TTT 5). The difference between the chemical shifts is
rather large (∆δ = 13.6) and can be used to recognize the
X and Y rings.
Scheme 10
Actually, the 13C NMR spectra of compounds 13
and 14 allowed us to unambiguously assign these two
compounds to the X2Y and XY2 isomers, respectively (see
Table 1).
Compound 7 can be unambiguously assigned to the
Y3 isomer based on the 13C NMR spectrum taking into
account the change in the chemical shift of the C(2) atom
upon the replacement of the phenyl group with the chloꢀ
rine atom (see Table 1).
This considerable difference in the chemical shifts of
the signals for C(2) of the X and Y rings is clear if the X
and Y rings are considered as the 4Hꢀ1,2,4ꢀtriazole and
In the case under consideration, an analogous ionic
bond cleavage would give rise to zwitterion 16, whose

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Tartakovsky et al.
1Hꢀ1,2,4ꢀtriazole derivatives, respectively. It is known8
that the signal for C(3) in the spectra of the latter comꢀ
pounds appears at lower field compared to the signal
for C(5).
for 1 h. The reaction solution was cooled to 20 °C. After 6 h, the
colorless crystals were filtered off and washed with a small
amount of cold benzene. Compound 7 was obtained in a yield of
1.2 g (20%), m.p. 311—313 °C (from toluene). Found (%):
C, 23.60; Cl, 34.84; N, 41.49. C6Cl3N9. Calculated (%):
C, 23.67; Cl, 34.93; N, 41.40. IR (KBr), ν/cm–1: 716, 757,
1081, 1237, 1269, 1449, 1629. MS, m/z: 303 [M]+.
*
*
*
B. Triazole 6 (190 mg, 1.4 mmol) was heated at 210—215 °C
for 10 min, at 240 °C for 15 min, and at 270 °C for 25 min. The
residue (140 mg) was separated by chromatography (CHCl3 as
the eluent). Compound 7, which was obtained in a yield of
25 mg (17%), was identical to that described above.
To summarize, we developed a procedure for the synꢀ
thesis of the Y3ꢀTTT system by thermal cyclization of
5ꢀsubstituted 3ꢀchloroꢀ1,2,4ꢀtriazoles. The X2YꢀTTT and
XY2ꢀTTT systems were synthesized for the first time. Sysꢀ
tems consisting of three nonannulated triazole rings were
prepared for the first time by the triazine ring opening in
TTT using nucleophiles. The triazole X and Y rings of
tris[1,2,4]triazolo[1,3,5]triazine can be distinguished with
certainty by 13C NMR spectroscopy.
3ꢀPhenylꢀ4ꢀ[3ꢀphenylꢀ4ꢀ(3ꢀphenylꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀyl)ꢀ
1,2,4ꢀtriazolꢀ5ꢀyl]ꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀone (8). А. Acidic hydrolyꢀ
sis. A solution of TTT 2 (100 mg, 0.23 mmol) in 86% formic
acid (1 mL) was refluxed for 6 h (TLC control; acetone—hexꢀ
ane, 1 : 1, as the eluent). The solution was concentrated and the
residue was dried at 80 °C in vacuo over P2O5. Triazolone 8 was
obtained in a yield of 100 mg (96%) as colorless crystals, m.p.
158—160 °C (from toluene). Found (%): C, 64.18; H, 3.71;
N, 28.66. C24H17N9O. Calculated (%): C, 64.42; H, 3.83;
N, 28.17. IR (KBr), ν/cm–1: 1688, 1721 (C=O). 1H NMR
(DMSOꢀd6), δ: 7.40—7.62 (m, 12 H); 7.84 (dd, 1 H, J ≈ 3 Hz,
J ≈ 7 Hz); 7.93 (d, 2 H); 12.50 (s, 1 H, NH); 15.20 (br.s,
1 H, NH). 13C NMR (DMSOꢀd6), δ: 125.5, 125.79, 125.84
(3 ipsoꢀPh); 126.1, 126.6, 128.2, 128.7, 129.0, 129.2 (6 оꢀ and
mꢀPh); 130.6, 130.8, 131.1 (3 pꢀPh); 145.1 (3J = 3.2); 153.6
Experimental
The IR spectra were recorded on a PerkinꢀElmer 577 specꢀ
trometer. The mass spectra were obtained on a Kratos MSꢀ30
instrument (EI, 70 eV); for the chlorineꢀcontaining fragments,
only the signals with the 35Cl isotope are given. The 1H and
13C NMR spectra were measured on a Bruker AMꢀ300 specꢀ
trometer operating at 300.13 and 75.5 MHz, respectively. The
assignment of the signals in the 13C NMR spectra was made
using spectra measured without proton decoupling, the INEPT
and DEPTꢀ135 experiments, and additive calculations. The reꢀ
actions were monitored by TLC (Silufol UVꢀ254) using silica
gel for column chromatography.
3ꢀAminoꢀ5ꢀphenylꢀ1,2,4ꢀtriazole (3a),9 3ꢀmethylthioꢀ5ꢀ
phenylꢀ1,2,4ꢀtriazole (3b),10 5ꢀchloroꢀ3ꢀphenylꢀ1,2,4ꢀtriazole
(4),11 and 3,5ꢀdichloroꢀ1,2,4ꢀtriazole (6)12 were prepared acꢀ
cording to procedures described earlier.
3,7,11ꢀTriphenyltris[1,2,4]triazolo[4,3ꢀa:4´,3´ꢀc:4″,3″ꢀe]ꢀ
[1,3,5]triazine (2). Compound 2 was synthesized according to a
known procedure3 and thoroughly dried at 120 °C in vacuo.
1H NMR (DMSOꢀd6), δ: 7.65 (m, 3 H); 8.05 (dd, 2 H, J =
1.9 Hz, J = 8.1 Hz). MS, m/z: 429 [M]+.
3
(3J = 5.2); 154.5 (3 C—Ph, J = 4.2 Hz); 143.7, 151.0 (br.s,
C=O), 155.6. MS, m/z: 446 [M – 1]+.
B. Alkaline hydrolysis. Compound 2 (100 mg, 0.23 mmol)
was dissolved with heating in DMF (1 mL). A solution of NaOH
(0.3 g) in water (0.3 mL) was added to the cold reaction soluꢀ
tion. The reaction mixture was stirred for 0.5 h, poured into
water with ice (20 g), and neutralized with concentrated aqueꢀ
ous HCl. The precipitate that formed was filtered off, washed
with water, and dried in vacuo over P2O5. Compound 9 was
obtained in a yield of 95 mg (92%). The product is identical to
that prepared under acidic hydrolysis conditions.
5ꢀ(3ꢀChloroꢀ5ꢀphenylꢀ1,2,4ꢀtriazolꢀ4ꢀyl)ꢀ3ꢀphenylꢀ4ꢀ
(5ꢀphenylꢀ1Hꢀ1,2,4ꢀtriazolꢀ3ꢀyl)ꢀ1,2,4ꢀtriazole (9). Antimony
pentachloride (10 mg, 0.03 mmol) was added to a solution of 2
(100 mg, 0.23 mmol) in dry dioxane (3 mL). Gaseous HCl was
passed through the refluxing reaction mixture for 3 h. Then a
new portion of SbCl5 (10 mg, 0.03 mmol) was added, and HCl
was passed for 2 h. After consumption of the starting compound
(TLC control; EtOAc—hexane, 3 : 1, as the eluent), the soluꢀ
tion was cooled and the solvent was distilled off in vacuo. The
residue was thoroughly washed with ice water (20 mL) and
extracted with CHCl3 (30 mL). The extract was dried with
MgSO4 and the solvent was distilled off in vacuo. The residue
was dried in vacuo at 80 °C over P2O5. Compound 9 was obꢀ
tained in a yield of 90 mg (83%) as colorless crystals, m.p.
217—218 °C (from acetone). Found (%): C, 61.59; H, 3.30;
Cl, 7.90; N, 26.68. C24H16ClN9. Calculated (%): C, 61.87;
H, 3.46; Cl, 7.61; N, 27.06. 1H NMR (DMSOꢀd6), δ: 7.45—7.57
(m, 11 H); 7.65 (d, 2 H, J = 6.9 Hz); 7.77 (dd, 2 H, J ≈ 3 Hz,
J ≈ 7 Hz); 12.00 (s, 1 H, NH). 13C NMR (DMSOꢀd6), δ: 124.5,
124.8, 125.5 (3 iꢀPh); 126.1, 127.1, 128.3 (3 oꢀPh); 128.8, 129.2*
(3 mꢀPh); 131.2*, 131.3 (3 pꢀPh); 142.3, 142.7, 150.3 (br.s);
155.0 (3J = 4.2 Hz); 155.4 (3J = 4.0 Hz); 155.9 (br.s). MS, m/z:
429 [M – HCl]+.
2,6,10ꢀTriphenyltris[1,2,4]triazolo[1,5ꢀa:1´,5´ꢀc:1″,5″ꢀe]ꢀ
[1,3,5]triazine (5). А. Chlorotriazole 4 (360 mg, 2 mmol) was
heated at 230 °C for 0.5 h and then at 270 °C for 0.5 h. The
reaction was accompanied by HCl elimination. Then the reacꢀ
tion mixture was cooled and washed on a filter with acetone
(8 mL). Compound 5 was obtained in a yield of 130 mg (46%) as
colorless crystals, m.p. 390—400 °C (with decomp.). Found (%):
C, 67.31; H, 3.54; N, 29.27. C24H15N9. Calculated (%): C, 67.13;
H, 3.52; N, 29.35. IR (KBr), ν/cm–1: 729, 1123, 1337, 1445,
1
1625. H NMR (DMSOꢀd6), δ: 7.66 (m, 3 H); 8.32 (dd, 2 H,
J ≈ 3 Hz, J ≈ 7 Hz). MS, m/z: 429 [M]+.
B. A solution of triazole 4 (300 mg, 1.7 mmol) in dry sulfolane
(3 mL) was heated at 250 °C for 0.5 h and at 270 °C for 1 h. After
cooling, the reaction mixture was poured into water (20 mL).
The precipitate was filtered off and washed on a filter with
acetone. Compound 5, which was identical to that prepared
above, was obtained in a yield of 30 mg (12%).
2,6,10ꢀTrichlorotris[1,2,4]triazolo[1,5ꢀa:1´,5´ꢀc:1″,5″ꢀe]ꢀ
[1,3,5]triazine (7). А. A solution of triazole 6 (8 g, 58 mmol) in
dry sulfolane (15 mL) was heated at 250 °C for 1 h and at 270 °C

Synthesis of tris[1,2,4]triazolo[1,3,5]triazines
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 3, March, 2005
725
3ꢀPhenylꢀ1ꢀ[3ꢀphenylꢀ1ꢀ(3ꢀphenylꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀyl)ꢀ
1,2,4ꢀtriazolꢀ5ꢀyl]ꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀone (10). Compound 5
(100 mg, 0.23 mmol) was dissolved in a minimum amount of hot
DMF. A solution of NaOH (3 g) in water (4 mL) was added to
the reaction solution cooled to 30 °C. The reaction mixture was
stirred for 20 min, poured into ice water (50 mL), and neutralꢀ
ized with a concentrated aqueous HCl solution. The precipitate
was filtered off, the filtrate was extracted with EtOAc (2×20 mL),
and the extract was dried with MgSO4. After evaporation of the
solvent, the residue was combined with the precipitate that reꢀ
mained after filtration, and the mixture was washed with water
and dried in vacuo at 100 °C over P2O5. Compound 10 was
obtained in a yield of 90 mg (77%), m.p. 296—299 °C (from a
EtOH—H2O mixture, 5 : 1). Found (%): C, 64.09; H, 4.07;
N, 28.24. C24H17N9O. Calculated (%): C, 64.42; H, 3.83;
N, 28.17. IR (KBr), ν/cm–1: 1720 (C=O). 1H NMR
(DMSOꢀd6), δ: 7.50—7.62 (m, 9 H); 7.88 and 7.98 (both m,
2 H each); 8.16 (d, 2 H, J = 6.8 Hz); 12.50 and 12.90 (both br.s,
1 H each, NH). 13C NMR (DMSOꢀd6), δ: 125.7, 126.3, 129.4
(3 iꢀPh); 125.5, 126.2* (3 mꢀPh); 129.1, 129.17, 129.24 (3 oꢀPh);
130.4, 130.9, 131.2 (3 pꢀPh); 146.1 (C(5), ring B); 147.7 (C(3),
331—334 °C (at this temperature, 13 was partially isomerized
into TTT 14). Found (%): C, 67.21; H, 3.50; N, 28.97.
C24H15N9. Calculated (%): C, 67.13; H, 3.52; N, 29.35.
IR (KBr), ν/cm–1: 694, 731, 1447, 1600. 1H NMR (DMSOꢀd6),
δ: 7.58—7.62 (m, 3 H); 7.65—7.76 (m, 6 H); 8.05—8.11 (m, 6 H).
MS, m/z: 429 [M]+.
3,6,10ꢀTriphenyltris[1,2,4]triazolo[1,5ꢀa:1´,5´ꢀc:4″,3″ꢀe]ꢀ
[1,3,5]triazine (14). А. Compound 2 was heated at 230 °C for 3 h.
As a result, TTT 2 remained intact.
In an independent experiment, TTT 2 (100 mg, 0.23 mmol)
was heated for 0.5 h with a gradual increase in the temperature
from 330 to 360 °C. After cooling, the reaction mixture was
extracted with hot acetone, and the solvent was distilled off
in vacuo. The residue contained compound 14 and traces of
compounds 1 and 13 (TLC). The chromatographic purification
of the residue (CHCl3—EtOAc, 2 : 1, as an eluent) afforded
trimer 14 in a yield of 80 mg (80%) as colorless crystals, m.p.
307—310 °C (from acetone). Found (%): C, 67.32; H, 3.49;
N, 29.18. C24H15N9. Calculated (%): C, 67.13; H, 3.52; N, 29.35.
IR (KBr), ν/cm–1: 693, 727, 1447, 1620. 1H NMR (DMSOꢀd6),
δ: 7.56—7.77 (m, 9 H); 8.08—8.18 (m, 4 H); 8.28—8.34 (m, 2 H).
MS, m/z: 429 [M]+.
3
ring A, J = 4.3 Hz); 153.7 (C(5), ring A); 154.3 (br.s, C=O);
3
3
155.2 (C(3), ring C, J = 3.7 Hz); 160.8 (C(3), ring B, J =
4.4 Hz). MS, m/z: 447 [M]+.
B. Compound 13 (100 mg, 0.23 mmol) was heated at 330 °C
for 40 min to prepare compound 14 in a yield of 98 mg (98%).
The product is identical to that prepared according to the
method A.
3ꢀChloroꢀ1ꢀ[3ꢀchloroꢀ1ꢀ(3ꢀchloroꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀyl)ꢀ
1,2,4ꢀtriazolꢀ5ꢀyl]ꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀone (11). A solution of
NaOH (0.2 g) in water (0.5 mL) was added to a solution of
TTT 7 (80 mg, 0.26 mmol) in DMF (0.5 mL). The reaction
mixture was stirred for 15 min and poured into water with ice
(20 g). The solution was neutralized with a concentrated aqueꢀ
ous HCl solution and extracted with EtOAc (2×20 mL). The
extract was dried with MgSO4. The solvent was distilled off
in vacuo. The resulting oil was crystallized by adding a small
amount of CHCl3 and dried in vacuo at 80 °C over P2O5. Comꢀ
pound 11 was obtained in a yield of 52 mg (61%), m.p.
139—142 °C (from CHCl3). Found (%): C, 22.59; H, 0.97;
Cl, 32.59; N, 38.62. C6H2Cl3N9O. Calculated (%): C, 22.35;
H, 0.63; Cl, 32.98; N, 39.09. IR (KBr), ν/cm–1: 1779 (C=O).
1H NMR (DMSOꢀd6), δ: 14.45 (br.s, NH). 13C NMR
(DMSOꢀd6), δ: 138.6, 143.5 (br), 145.1, 151.3 (br), 151.5, 152.0.
MS, m/z: 321 [M]+.
This study was financially supported by the Federal
Target Program "Integration of Science and Higher
School" (Project No. IO 667).
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3ꢀChloroꢀ1ꢀ[3ꢀchloroꢀ1ꢀ(3ꢀchloroꢀ1Hꢀ1,2,4ꢀtriazolꢀ5ꢀyl)ꢀ
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in vacuo. Recrystallization of the residue from CHCl3 afforded
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Received November 1, 2004;
* Two superimposed signals.
in revised form December 20, 2004