Synthesis and structure of tris(5-phenyltetrazol-1-yl)methane

Article abstract of DOI:10.1007/s10593-007-0048-3

The interaction of 5-phenyltetrazolate anion with chloroform in strongly alkaline medium leads to the formation of tris(5-phenyltetrazol-1-yl)methane and 2-dichloromethyl-5-phenyltetrazole. The structures of tris(5-phenyltetrazol-1- yl)-methane and of its

Full text of DOI:10.1007/s10593-007-0048-3

Chemistry of Heterocyclic Compounds, Vol. 43, No. 3, 2007
SYNTHESIS AND STRUCTURE OF TRIS(5-PHENYLTETRAZOL-1-YL)METHANE
1
2
3
R. E. Trifonov , G. V. Gurskaya , A. V. Gaenko ,
4
1
V. E. Zavodnik , and V. A. Ostrovskii
The interaction of 5-phenyltetrazolate anion with chloroform in strongly alkaline medium leads to the
formation of tris(5-phenyltetrazol-1-yl)methane and 2-dichloromethyl-5-phenyltetrazole. The structures
of tris(5-phenyltetrazol-1-yl)-methane and of its isomer tris(5-phenyltetrazol-2-yl)methane have been
investigated by X-ray structural analysis and theoretical calculations carried out on the B3LYP/6-
3
1G** basis.
Keywords: polynuclear heterocycles, tetrazole, X-ray structural analysis, theoretical calculations by the
DFT method.
Polynuclear tetrazoles are considered as efficient ligands for binding metal ions [1, 2], and also as
potentially biologically active substances [3]. Information on polytetrazolylmethanes is limited in comparison
with other poly-N-azolylalkanes. We previously reported the synthesis of one such compound [4]. In the present
work we have investigated the reaction of 5-phenyltetrazolate anion with chloroform under various conditions
(
aqueous NaOH solutions of various concentration, in the presence or absence of a phase-transfer catalyst) and
also the structures of the compounds obtained.
Ph
Ph
Ph
Ph
H
N
N
N
CHCl3
N
NaOH
–
N
N
N
N
N
N
CHCl2
N
N
N
CH
N
N
2
N
1
N
3
3
5
Ph
CH
CHCl3
N
N
N
3
4
In alkaline medium 5-phenyltetrazole 1 dissociates with the formation of the corresponding anion 2, the
reaction of which with chloroform leads to 2-dichloromethyl-5phenyltetrazole (3) and tris(5-phenyltetrazol-1-
yl)methane (4). The presence of tris(5-phenyltetrazol-2-yl)methane (5) in the reaction products was not
_
_________________________________________________________________________________________
1
Saint Petersburg State Technological Institute (Technical University), Saint Petersburg 190013, Russia;
2
e-mail: va_ostrovskii@mail.ru. V. A. Engelgardt Institute of Molecular Biology, Russian Academy of Sciences,
Moscow 119991; e-mail: gurskayia@eimb.ru. Department of Theoretical Chemistry, Chemical Center, Lund
University, Lund, S-221 00, Sweden; e-mail: galev@inbox.ru. L. Ya. Karpov Research Institute for Physical
3
3
Chemistry, Moscow 105064, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 398-
4
04, March, 2007. Original article submitted August 3, 2006.
3
20 0009-3122/07/4303-0320©2007 Springer Science+Business Media, Inc.

observed. Probably in the first step anion 2 reacts with dichlorocarbene, generated from chloroform in strongly
alkaline medium, with the formation of a mixture of two regioisomers, 1- and 2-dichloromethyl-5-
phenyltetrazoles. 1-Dichloromethyl-5-phenyltetrazole is then converted into polynuclear tetrazole 4 by means of
a series of sequential reactions, in the course of which all the chlorine atoms are replaced by tetrazolyl
fragments. The corresponding 2-isomer 3 proved to be less reactive under analogous conditions. Apart from the
above-mentioned, the absence of tristetrazol-2-ylmethane 5 may also be explained by its low stability.
1
3
1
The structures of compounds 3 and 4 were confirmed by data of C and H NMR spectroscopy and also
by mass spectra. The structure of tris(5-phenyltetrazol-1-yl)methane 4 was investigated by X-ray structural
analysis and with the aid of quantum chemical-calculations.
Previously in [4] we mistakenly assumed that the interaction of anion 2 with chloroform in a
chloroform–aqueous sodium hydroxide solution system leads to the formation of compounds 5 and 3. The
results obtained in the present investigation indicate that in [4] the structure of the polynuclear tetrazole was
established incorrectly. Compound 4, formed in this reaction, is the product of the sequential substitution of
three chlorine atoms in the chloroform molecule by tetrazole fragments.
To increase the yield of polynuclear compound 4 by changing the reaction conditions for this process
was unsuccessful. Increasing the sodium hydroxide concentration to 40% increases the yield of 2-dichloro-
methyltetrazole 5 somewhat (up to 10%), while the formation of tristetrazole 4 was not recorded at all. A similar
situation is also observed on adding the phase transfer catalyst, tetrabutyl ammonium bromide, to the reaction
medium. In the latter case only compound 3 is also formed in 15% yield. The results enumerated above may be
explained both by interphase effects and by hydrolysis processes of the intermediate and final compounds 3, 4 to
the initial tetrazolate anion 2. In the latter case it is assumed that under these reaction conditions the stability of
the polynuclear 1H-substrates is greater than the stability of the 2H- isomers.
According to X-ray structural analysis data compound 4 in the condensed phase has a molecular
structure corresponding to the symmetry group C , in which all three phenyltetrazole fragments are identical
3
(
Fig. 1, Table 1). The phenyl substituents are oriented in one direction which enables the separating out of two
spatially distinct portions, polar and nonpolar, for this molecule. The hydrogen atom of the methine group is
disposed in a cavity surrounded by benzene rings. It may be expected that on retaining the molecular structure
the reactivity of this hydrogen atom will be small.
Fig. 1. Geometry of compound 4 determined by X-ray structural analysis.
3
21

TABLE 1. Sample Bond Lengths (d), Valence and Dihedral Angles (ω) for
Compound 4, Determined by X-ray Structural Analysis
Bond
d, Å
Angle
ω, deg.
Angle
ω, deg.
C
C
C
(1)–N(1)
(1)–N(5)
(1)–N(12)
1.450(5)
1.438(5)
1.437(5)
1.370(5)
1.372(5)
1.362(5)
1.356(5)
1.354(5)
1.357(6)
C
C
C
C
C
C
C
(1)–N(1)–N(2)
120.9(4)
121.3(4)
120.5(4)
-176.5
H
H
H
H
H
H
(1)–C(1)–N(1)–N(2)
(1)–C(1)–N(5)–N(6)
(1)–C(1)–N(12)–N(11)
(1)–C(1)–N(1)–C(2)
(1)–C(1)–N(5)–C(3)
(1)–C(1)–N(12)–C(4)
177.1
170.4
178.9
4.3
(1)–N(5)–N(6)
(1)–N(12)–N(11)
N
N
N
N
N
N
(1)–N(2)
(5)–N(6)
(12)–N(11)
(1)–C(2)
(5)–C(3)
(12)–C(4)
(1)–N(12)–N(11)–N(10)
(1)–N(1)–C(2)–N(4)
(1)–N(5)–C(3)–N(8)
(1)–N(12)–C(4)–N(9)
174.0
-3.8
174.7
3.9
175.9
C
C
(1)–N(1)–N(2)–N(3)
(1)–N(5)–N(6)–N(7)
-174.7
-75.8
The geometry, dipole moments, and total energy of compound 4 and its isomer, the hypothetical
tristetrazol-2-ylmethane 5 in the gas phase were calculated using the DFT quantum-chemical method with full
optimization on the basis B3LYP//6-31G** (Table 2). As may be noted from Fig. 2 and Table 2 the structure of
compound 4, optimized theoretically, is not in poor agreement with X-ray structural analysis data. Both in the
crystalline state and in the gas phase the geometry of this molecule is close to symmetry group C . For this
3
compound significant differences between the theoretically optimized and experimentally determined geometries
are displayed only in the values of the torsion angles between the planes of the tetrazole rings and the axis
passing through the C-H bond of the methine fragment. According to the data of theoretical calculations these
angles are ~45°, while according to X-ray structural analysis data they are ~0°.
Fig. 2. Geometry of compound 4 optimized on the B3LYP/6-31G** basis.
The difference may be caused by the effects of molecular packing in the crystal. The optimized geometry
of compound 5 differs in principle from the geometry of compound 4 (Fig. 3). The absence of symmetry is a
characteristic of the molecular structure of compound 5. In this compound the hydrogen atom of
the methine group is spatially available. The tetrazole fragments are significantly removed from one another. At
3
22

Table 2. Results of Calculations by the B3LYP/6-31G** Method for
Compounds 4 and 5*
l, Å
ω, deg
Bond
Angle
4
5
4
5
C
C
C
C
(1)–H
1.087
1.453
1.453
1.453
—
1.090
1.453
1.447
1.444
1.344
1.296
1.373
1.331
—
H–C(1)–N(5)
108.3
—
108.3
106.7
106.8
—
(1)–N(5)
(1)–N(12)
(1)–N(1)
H–C(1)–N(1)
H–C(1)–N(12)
H–C(1)–N(5)–C(3)
—
46.0
132.0
—
N
N
N
N
N
N
N
N
(1)–N(2)
(2)–N(3)
(3)–C(2)
(4)–N(1)
(5)–N(6)
(6)–N(7)
(7)–N(8)
(8)–C(3)
N(5)–C(3)–C(11)–C(16)
—
—
C
(18)–C(17)–C(4)–N(9)
0
—
—
1.365
1.283
1.364
1.319
—
—
—
—
C
C
(2)–N(4)
(3)–N(5)
1.331
–
1.366
_
______
*
For numbering of atoms see Figs. 2 and 3; total energy, E, a.u.:
-
(
1504.81202 (compound 4), 1504.84669 (compound 5); µ, D: 12.6
compound 4), 2.8 (compound 5).
the same time for compound 4, according to the theoretical and experimental data, the phenyltetrazole groups
have a nonplanar structure, in the case of tristetrazol-2-ylmethane 5 the torsion angle between the planes of the
benzene and tetrazole rings is ~0°.
Fig. 3. Geometry of compound 5 optimized on the B3LYP/6-31G** basis.
3
23

We note that the reactivity of the methine fragment hydrogen atom must play a definite role in the
majority of chemical conversions involving tristetrazolylmethanes. In the case of compound 4 the availability of
this hydrogen atom is limited by spatial factors (Figs. 1, 2). It might be expected that just this circumstance
determines the high stability of compound 4 in comparison with heterocycle 5, the isolation of which in the free
state was unsuccessful.
According to the data of the theoretical calculations (Table 2), tristetrazol-1-ylmethane 4 is
thermodynamically less preferred by 21.76 kcal/mol in comparison with the isomeric tristetrazol-2-ylmethane 5.
However the anomalously high value of µ for the 1-isomer 4 enables its significant stabilization in the condensed
phase to be expected due to intermolecular interactions.
EXPERIMENTAL
1
13
The H and C NMR spectra were recorded on a Bruker DPX 300 spectrometer (300 and 75 MHz
respectively) in DMSO, internal standard was the solvent signal. The IR spectra were recorded on a Shimadzu
FTIR 8400 instrument in KBr disks. Elemental analysis was carried out on a Hewlett-Packard 185B C,H,N
analyzer. Mass spectra were recorded on a Varian MAT 311 instrument, ionization was at 70 eV. Melting points
were determined on a PTP type instrument with a heating rate of 1°C/min in the melting range.
X-ray Structural Investigation of Compound 4. The intensities of 1850 independent reflections were
measured on a CAD 4 diffractometer (MoKα radiation with β-filter, θ/2θ scanning). Crystals of compound 4,
obtained from the system DMF–ethanol were triclinic, belonging to the space group Pī, a = 9.204(2),
3
b = 13.096(3), c = 14.886(3) Å, α = 102.85(3), β = 93.99(3), γ = 95.21(3)°, V = 1734.7(6) Å , Z = 2
3
[
C H N .3C H NO (DMF), one molecule of DMF is disordered], d = 1.278 g/cm ; M = 448.45. In the
2
2
16 12
3
7
calc
refinement 1699 independent reflections with I>2σ(I) were used. The structure was solved by the direct method
in an anisotropic appoximation for the non-hydrogen atoms. The coordinates of the hydrogen atoms were
established from an electron density difference map and were refined isotropically. The final value of the R
factor, calculated on 1699 reflections, was 0.033. All calculations were carried out using the program SHELX 97
[5].
Theoretical Investigation of Compounds 4, 5. Theoretical calculations by the DFT method on the
B3LYP//6-31G** basis (full optimization of the structure on the basis indicated) were carried out using the
Molcas 6.2 program [6].
Compounds 3, 4 (General Procedure). Chloroform (25 ml) was added in portions with vigorous
o
stirring during 1 h at 45 C to a solution of 5-phenyltetrazole (5 g, 34 mmol) in 25% NaOH solution (75 ml). The
reaction mixture was maintained at the same temperature for a further 6 h, cooled, and poured into ice-water
(
200 ml). The obtained mixture was treated with ether (100 ml). The solid precipitated at the phase separation
boundary was filtered off, washed with water, and with ether, and dried. Compound 4 (1.2 g, 23% calculated on
the initial 5-phenyltetrazole 1) was obtained, and was then purified by recrystallization from DMF–ethanol. The
ether extract was washed with water, dried, and evaporated. The residue was decolorized on a column of silica
gel, using chloroform as eluent. Compound 3 (0.3 g, 4%) was obtained, and was purified further by
recrystallization from aqueous ethanol.
2
-Dichloromethyl-5-phenyltetrazole (3). Cream-colored crystals, mp 93°C (from aqueous ethanol). IR
-
1
spectrum, ν, cm : 2950, 2890 (CH), 1704, 1616, 1544, 1472, 1422, 1355, 1260, 1200, 1145, 1130, 1025, 920
tetrazole). H NMR spectrum, δ, ppm: 9.52 (1H, s, CH); 8.13, 7.65 (5H, m, C H ). C NMR spectrum, δ, ppm:
1
13
(
6
5
7
6.45 (CH); 125.53, 126.94, 129.56, 131.68 (C H ); 165.64 (tetrazole). Mass spectrum, m/z (I, %): 230, 228 (7)
6 5
+
[M] ,202, 200 (19); 167, 165 (100); 140, 138 (69); 104, 103 (93); 89 (7); 77 (60); 63 (17); 51 (15). Found, %:
C 42.3; H 2.5; N 24.9. C H Cl N . Calculated, %: C 42.1; H 2.6; N 24.6.
8
6
2
4
3
24

Tris(5-phenyltetrazol-1-yl)methane (4). Colorless crystals, mp 155°C (decomp., from DMF–ethanol).
-
1
IR spectrum, ν, cm : 2960 (CH); 1605, 1535, 1470, 1448, 1425, 1360, 1260, 1170, 1095, 1075, 1030, 1000, 925
1
13
(
7
3
tetrazole). H NMR spectrum, δ, ppm: 9.28 (1H, s, CH); 7.62, 7.38 (15H, m, C H ). C NMR spectrum, δ, ppm:
6
5
+
2.96 (CH); 121.64, 129.14, 129.29, 132.13 (C H ); 155.04 (tetrazole). Mass spectrum, m/z (I, %): 448 (1) [M] ;
6 5
64, 363 (11); 349 (4); 337 (3); 288 (3); 273 (6); 246, 245 (100); 221 (5); 146 (7); 129 (8); 118 (50); 103 (32).
Found, %: C 59.1; H 3.8; N 37.8. C H N . Calculated, %: C 58.9; H 3.6; N 37.5.
2
2
16 12
The work was carried out with the use of equipment of the regional Center of Collective Use "Material
Science and Diagnostics in Advanced Technologies" with the support of the Russian Fund for Fundamental
Investigations (RFFI) (grant 05-03-32366).
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