Optimization of the synthesis of 2-phenyl-1,2,3-triazole

Article abstract of DOI:10.1007/s10593-010-0473-6

The synthesis of 2-phenyl-1,2,3-triazole by the cyclization of glyoxal phenylosazone in high-boiling solvents in the presence of copper triflate catalyst has been optimized. The structure of the product was confirmed by data of IR, ¹H, ¹³C, and ¹⁵N NMR spectroscopy, mass spectrometry, and elemental analysis.

Full text of DOI:10.1007/s10593-010-0473-6

Chemistry of Heterocyclic Compounds, Vol. 46, No. 1, 2010
OPTIMIZATION OF THE SYNTHESIS
OF 2-PHENYL-1,2,3-TRIAZOLE
G. F. Myachina1*, T. G. Ermakova1, N. P. Kuznetsova1, R. G. Sultangareev1,
L. I. Larina1, L. V. Klyba1, G. T. Suchanov2, and B. A. Trofimov1
The synthesis of 2-phenyl-1,2,3-triazole by the cyclization of glyoxal phenylosazone in high-boiling
solvents in the presence of copper triflate catalyst has been optimized. The structure of the product was
1
confirmed by data of IR, H, 13C, and 15N NMR spectroscopy, mass spectrometry, and elemental
analysis.
Keywords: aniline, glyoxal bis(phenylhydrazone), 2-phenyl-1,2,3-triazole, cyclization.
2-Phenyl-1,2,3-triazole is a promising starting material for the synthesis of 4-nitro-1,2,3-triazole, which
is energetically a reactive material as a component of explosive compositions, reactive fuel [1]. Previously, the
synthesis of 2-phenyl-1,2,3-triazole was reported [2, 3] by the cyclization of glyoxal phenylosazone in the
presence of Cu2SO4 at 75-80oC (yield was 50-59%). Later the possibility of synthesizing 2-phenyl-1,2,3-triazole
was shown by heating glyoxal phenylosazone to 180-210oC with a catalytic amount of CuCl (yield was 66.6%)
[4], and also using a combined catalyst CuCl/CaCl2 (yield was 75%) [5].
With the aim of optimizing the synthesis of 2-phenyl-1,2,3-triazole (2) (increase of yield, purity of
product, and acceleration of the process) we have studied the cyclization of glyoxal phenylosazone 1 using
copper triflate, Cu(OSO2CF3)2, and also high-boiling solvents: o-xylene, toluene, and ethylene glycol [6]. The
synthesis of the 1,2,3-triazole 2 was effected according to the following scheme:
5
4
Ph
∆
H2NPh
N
N
+
N
N N
3
1
H
catalyst
N 2
NH
3
Ph
Ph
1
2
_______
* To whom correspondence should be addressed, e-mail: myachina@irioch.irk.ru.
1Irkutsk A. E. Favorsky Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, Irkutsk
664033, Russia.
2Institute of Problems of Chemical and Energetic Technologies, Siberian Branch of the Russian Academy of
Sciences, Biisk 659322, Russia; e-mail: admin@ipcet.ru.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 91-94, January, 2010. Original
article submitted July 14, 2009.
0009-3122/10/4601-0079©2010 Springer Science+Business Media, Inc.
79

TABLE 1. Dependence of the Yield of Compound 2 on the Time of
Cyclization of Substance 1 in Various Solvents (according to data of
1H NMR spectroscopy)
Reaction
time, h
Reaction
time, h
Reaction
time, h
Yield 2, %*
Yield 2, %*2
Yield 2, %*3
0.5
1.0
1.5
2.5
5.0
6.0
20
25
0.5
1.0
2.0
5.5
65
75
0.5
1.0
1.4
2.0
85
90
34
50
85
100
95
100
85
100
_______
* Solvent toluene, reaction temp. 110oC.
*2 Solvent o-xylene, reaction temp.140oC.
*3 Solvent ethylene glycol, reaction temp. 190oC.
The effect of the amount of catalyst on the yield of compound 2 on cyclization of substance 1 (without
using solvent) was investigated previously in [6]. It was established that the optimum catalyst content in the
reaction mixture was 5%, which was used in the present work.
In the presence of copper triflate in high-boiling solvents the cyclization of the initial compound 1 began
at 100oC with subsequent self-heating to the boiling point of the solvent. The reaction kinetics was studied using
the 1H NMR method (by the relative change of integral intensities of compounds 1 and 2). It was established that
after 0.5 h the cyclization of substance 1 was effected in toluene by 20, o-xylene by 65, and ethylene glycol by
85%. The end of the reaction was reached after 6, 5.5, and 2 h respectively (Table 1).
Reaction proceeds rapidly in a medium of ethylene glycol (2 h), which is obviously caused by the high boiling
point of the solvent (190oC). In toluene, cyclization of compound 1 is complete after 6 h, but the reaction
temperature is significantly lower (110oC).
In the process of cyclizing substance 1 aniline 3 was formed together with the desired product 2. Product
2 (first fraction) was isolated by column chromatography in a high degree of purity (99.96-100%, according to
data of chromato-mass spectrometry). The structure of product 2 was confirmed by data of IR, 1H, 13C, and 15N
NMR spectroscopy, mass spectrometry, and elemental analysis.
1
A resonance signal was observed in the H NMR spectra of compound 2 for the protons of the triazole
ring at 8.11 ppm and resonance signals were also observed for the protons of the phenyl fragment. In the 13C
NMR spectra there were resonance signals for the carbon atoms of the phenyl ring, and also a resonance signal
for atoms C-4,5 of the triazole ring (136.47 ppm). The two-dimensional H1–N15 HMBC (I) spectrum indicates
the presence of two signals for nitrogen at 58.6 and 120.2 ppm, assigned respectively to the N-1,3 and N-2
1
atoms. In fact a cross peak was observed in the H–15N 2D spectrum for atoms N-1,3 with the protons of the
triazole ring, and also a cross peak for the N-2 atom both with the protons of the triazole ring and with the ortho
and meta protons of the phenyl ring.
The use of a new catalyst (copper triflate) and high-boiling solvents (toluene, o-xylene, ethylene glycol)
therefore enabled us to optimize the reaction process and to obtain 1,2,3-triazole 2 with a high degree of purity
(99.9%), in high yield (82-90%), and also to simplify its isolation stage.
EXPERIMENTAL
The IR spectra were obtained on a Bruker IFS-25 instrument in a microlayer. The 1H, 13C, and 15N NMR
spectra were recorded on Bruker DPX-400 and AV-400 spectrometers (400, 101 and 40 MHz
80

1
respectively) in DMSO-d6 at 25oC. Chemical shifts for H and 13C NMR were measured relative to TMS.
Chemical shifts for 15N NMR were measured relative to nitromethane with a precision of 0.1 ppm using the 2D
1
procedure for H–15N NMR HMBC. The mass spectra after electron ionization (70 eV) were recorded on a
Shimadzu GCMS-QP5050A instrument (quadrupole mass-analyzer, mass detection range 34-650 a.m.u.).
Chromatographic separation was carried out on a SPB-5 ms capillary column (60 m×0.25 mm×0.25 µm), carrier
gas helium, flow rate 0.7 ml/min, evaporator and ion source temperature was 250oC, pressure 250 kPa,
programing mode: from 70 to 250oC at 10 deg/min. A check on the progress of reactions and the homogeneity
of synthesized compounds was effected by TLC on Silufol UV–254 plates (visualization with a UV lamp).
Preparative separation was carried out by column chromatography on LSL254 silica gel (5/40 µ).
Glyoxal Bis(phenylhydrazone) (1) was obtained by the known procedure of [7]. 1H NMR spectrum, δ,
ppm (J, Hz): 6.75 (2H, t, J = 8.1, p-C6H5); 6.97 (4H, d, J = 8.1, o-C6H5); 7.20 (4H, t, J = 8.1, m-C6H5); 7.64 (2H,
s, =CH); 10.36 (2H, br. s, NH). 13C NMR spectrum, δ, ppm: 111.98 (o-C6H5); 118.97 (p-C6H5); 129.17
(m-C6H5); 144.84 (ipso-C6H5); 136.95 (=CH).
2-Phenyl-1,2,3-triazole (2). A mixture of compound 1 (1 g, 0.042 mmol) and copper triflate
Cu(OSO2CF3)2 (0.05g, 0.14 mmol) in toluene (10 ml) was stirred and boiled in a stream of argon at 110oC for
5 h. The solvent was evaporated under reduced pressure (15 mm Hg). The oily residue was chromatographed on
a column of silica gel in the system hexane–ether, 1:2. Compound 2 (0.55 g, 90%) was isolated having bp 96oC
20
(10 mm Hg), nD 1.5875, Rf 0.94 (eluent hexane–ether, 1:2). Found, %: C 66.23; H 5.09; N 28.55. C8H7N3.
Calculated, %: C 66.21; H 4.83; N 28.97.
The kinetics of the process was studied by taking out test samples after definite time intervals (Table 1).
Compound 2 was obtained in o-xylene or ethylene glycol at the boiling point of the solvent (see Table 1)
and isolated analogously to the first synthesis. IR spectrum, ν, cm-1: 3139, 3124, 1410, 1376, 1260 (C–H triazole
1
ring), 694, 755, 1476, 3036, 3059, 3080 (C6H5). H NMR spectrum, δ, ppm (J, Hz): 7.41 (1H, t, J = 8.0,
p-C6H5); 7.55 (2H, t, J = 8, m-C6H5); 8.03 (2H, d, J = 8.0, o-C6H5); 8.11 (2H, s, H-4,5). 13C NMR spectrum, δ,
ppm: 118.50 (o-C6H5); 127.75 (p-C6H5); 129.73 (m-C6H5); 136.47 (C-4,5); 139.31 (ipso-C6H5). Mass spectrum,
m/z (Irel, %): 145 [M]+• (99), 118 [M-HCN]+• (17), 91 [NPh]+• (100), 77 [Ph]+• (11), 64 (39), 63 (22), 59 (15), 51
[C4H3]+ (27).
REFERENCES
1.
2.
3.
4.
H. H. Licht and H. Ritter, J. Energ. Mater., 12, 223 (1994); Chem. Abstr., 122, 137599 (1995).
J. L. Riebsomer, J. Org. Chem., 13, 815 (1948).
B. M. Lynch and T.-L. Chan, Canad. J. Chem., 41, 274 (1963).
Yu. A. Naumov, Methods of Obtaining Chemical Reagents and Compounds [in Russian], Khimiya,
Moscow (1969), Part 18, p. 196.
5.
6.
L. I. Vereshchagin, V. M. Nikitin, V. I. Meshcheryakov, G. A. Gareev, L. P. Kirillova, and
V. M. Shul'gina, Zh. Org. Khim., 25, 1744 (1989).
B. A. Trofimov, G. V. Sakovich, G. F. Myachina, T. G. Ermakova, N. P. Kuznetsova, L. I. Volkova,
R. G. Sultangareev, G. T. Sukhanov, and S. V. Sysolyatin, Russ. Pat. 2344130; Byull. Izobret., No. 2
(2009).
7.
A. D. Murray and D. L. Williams, Syntheses of Organic Compounds with Hydrogen Isotopes [Russian
translation], Izd. Inostr. Lit., Moscow (1961), p. 137.
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