Tautomerism of aza cycles: II. Synthesis and structure of 5-substituted 3-(2-hydroxyethylsulfanyl)-1H-1,2,4-triazoles and their salts. Preference of the 1H,4H-1,2,4-triazolium tautomers

Article abstract of DOI:10.1134/S1070363208030225

New complexing agents, potentially tautomeric 3-(2-hydroxyethylsulfanyl)- 1H-1,2,4-triazole, its 5-methyl-and 5-phenyl-substituted analogs, and some their salts, were synthesized, and their structure was discussed on the basis of the ¹H and ¹³C NMR, IR, and mass spectra, X-ray diffraction data, and published data. In keeping with the rule formulated previously for N-unsubstituted 1,2,4-triazoles having dissimilar substituents, the synthesized compounds were found to exist as 3-(2-hydroxyethylsulfanyl)-5-R-1H-1,2,4- triazole tautomers (3-R_A-5-R_D-1H-1,2,4-triazoly). They are protonated at the nitrogen atom in position 4 of the triazole ring. The ¹H and ¹³C NMR spectra of these compounds in trifluoroacetic acid suggest the presence of two forms due to equilibrium between the neutral and protonated species. Analysis of the crystallographic data for the triazolium salts and published data showed preference of the 1H,4H-1,2,4-triazolium tautomer.

Full text of DOI:10.1134/S1070363208030225

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 3, pp. 461–479. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © B.I. Buzykin, E.V. Mironova, V.N. Nabiullin, N.M. Azancheev, L.V. Avvakumova, I.Kh. Rizvanov, A.T. Gubaidullin, I.A. Litvinov,
V.V. Syakaev, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 3, pp. 476–494.
Tautomerism of Aza Cycles: II.1 Synthesis and Structure
of 5-Substituted 3-(2-Hydroxyethylsulfanyl)-1H-1,2,4-triazoles
and Their Salts. Preference of the 1H,4H-1,2,4-Triazolium
Tautomers
B. I. Buzykin, E. V. Mironova, V. N. Nabiullin, N. M. Azancheev, L. V. Avvakumova,
I. Kh. Rizvanov, A. T. Gubaidullin, I. A. Litvinov, and V. V. Syakaev
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
e-mail: buz@iopc.knc.ru
Received May 13, 2007
Abstract—New complexing agents, potentially tautomeric 3-(2-hydroxyethylsulfanyl)-1H-1,2,4-triazole, its 5-
methyl- and 5-phenyl-substituted analogs, and some their salts, were synthesized, and their structure was
discussed on the basis of the 1H and 13C NMR, IR, and mass spectra, X-ray diffraction data, and published data.
In keeping with the rule formulated previously for N-unsubstituted 1,2,4-triazoles having dissimilar
substituents, the synthesized compounds were found to exist as 3-(2-hydroxyethylsulfanyl)-5-R-1H-1,2,4-
triazole tautomers (3-RA-5-RD-1H-1,2,4-triazoly). They are protonated at the nitrogen atom in position 4 of the
1
triazole ring. The H and 13C NMR spectra of these compounds in trifluoroacetic acid suggest the presence of
two forms due to equilibrium between the neutral and protonated species. Analysis of the crystallographic data
for the triazolium salts and published data showed preference of the 1H,4H-1,2,4-triazolium tautomer.
DOI: 10.1134/S1070363208030225
Sulfanyl derivatives of 1,2,4-triazoles, including
those having a substituent on the sulfur atom, exhibit
versatile biological activity, such diuretic, neuroleptic
[2], antituberculous [3, 4], antimicrobial [5],
antiphlogistic [6], antiarthritic [7], antimycotic [8],
anti-HIV [9], etc.; they act as inhibitors of matrix
metalloprotease [11] and CXXR2 receptor antagonists
[12] and have been proposed for the treatment of
various diseases, in particular of mental disorders [13].
Substituted sulfanyl-1,2,4-triazoles have found
application in agriculture and industries [14, 15], as
complexing agents capable of coordinating metal ions
at different donor centers [16, 17], as precursors in
organic synthesis [18], etc. [19, 20].
tautomerism. Among three possible preferential
tautomers A–C, only alkylsulfanyl-5-R-1H-tautomer
(B, X = AlkS, Y = H, Me, Ph) was detected in crystal
and in solution. These data are consistent with the
conclusion drawn in [1], according to which 3-RA-5-
RD-1H-1,2,4-triazole tautomer is more favorable for
1,2,4-triazoles having no substituent on the nitrogen
atom (RA and RD are substituents exhibiting,
respectively, electron-withdrawing and electron-donor
effect).
H
X
H
Y
N
N
N
N
N
N
Y
X
Y
X
In the preceding communication [1] we reported
that, unlike hydrogen atom or methyl or phenyl group),
alkylsulfanyl groups exhibit electron-withdrawing
effect and that N-unsubstituted 1,2,4-triazoles having
an alkylsulfnayl group do not give rise to annular
N
N
N
H
C
A
B
In going to C-sulfanyl-1,2,4-triazoles (X or Y =
SH), the situation is complicated as a result of
appearance of additional tautomers due to SH group
* For communication I, see [1].
461

462
BUZYKIN et al.
(thione forms D and E) [19–21]. For example, 3(5)-
sulfanyl-1,2,4-triazole in crystal exists as 3,4-dihydro-
1H-1,2,4-triazole-5-thione (tautomer D), while the
structure of 5(3)-sulfanyl-3(5)-phenyl-1H-1,2,4-triazole
in crystal depends on the crystallization conditions
[21] (the details will be reported elsewhere).
which must be taken into account while determining
the structure of such derivatives. When the XH group
is sufficiently acidic (XH = COOH, SH, SO2OH, etc.),
internal salts like J may be formed.
H
H
Y
H
H
N
N
N
N
N
N
N
N
N
N
N
N
Y
Y
Y
ZBXH
ZBXH
H
N
N
Y
SH
Y
SH
N
N
A''
B''
A'
B'
H
H
N
N
X
B
Z
X
B
Z
H
S
H
H
Y
Y
N
N
N
N
N
N
H
F
Y
S
N
N
G
H
H
H
D
E
N
N
In the recent years, examples of various ring–chain
tautomerism of 1,2,4-triazoles have been reported [22,
23]. For instance, the NH fragment of 1,2,4-triazole
having no substituent on the nitrogen reversibly adds at
an A=B double bond (C=C, C=O, C=N, C=S) in the
substituent on the carbon atom, as was shown in [22].
The possibility for such tautomeric transformation is
responsible for many processes leading to fused 1,2,4-
triazoles (see, e.g., [18–20]).
Y
XBZH
XBZH
N
N
H
I
H
N
Y
N
ZBX_
+
N
H
J
H
H
B
Z
N
N
N
N
A
Y
Y
Z
Z
A
B
The present article reports on the results of studying
the structure of 1,2,4-triazole derivatives where ABXH =
SCH2CH2OH and their salts. 5-Substituted 3-(2-hydro-
xyethylsulfanyl)-1,2,4-triazoles I–III were synthesized
by alkylation of the corresponding 5-R-3-sulfanyl-1H-
1,2,4-triazoles (R = H, Me, Ph) with 2-chloroethanol in
alkaline medium; compounds I–III are capable of
forming salts with many acids and complexes with
most transition metal ions. Triazoles I–III were
isolated from the reaction mixtures as transparent
syrupy materials which crystallized only after a long
time. For example, triazole I turned crystalline in
almost 1.5 year; the crystallization was not complete,
and it was fairly difficult to separate crystals from the
semiliquid material. The methyl- and phenyl-
substituted analogs crystallized more readily,
especially after treatment of their solutions with silica
gel. The spectral parameters of their syrup-like and
crystalline samples were almost identical.
N
N
BH
N
N
A
Y
N
One more group of potentially tautomeric 1H-1,2,4-
triazoles, as well of other azoles and azines, includes
derivatives in which the ZB–XH moiety possessing a
labile hydrogen atom is separated from the heteroring
by ZB spacer. For example, ZB is an aliphatic chain,
and XH = OH [3], COOH [24], SH, NHR (including
NH-heterorings) [19–21, 23], etc. Such 1H-1,2,4-
triazole derivatives give rise to another kind of ring–
chain tautomerism [A″(B″) → F(G)] involving
formation of a spiro-fused system. If the bridging
chain in these compounds is linked to the triazole ring
through a heteroatom (either the same or other),
rearrangements like A″ → H or B″ → I may occur,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

TAUTOMERISM OF AZA CYCLES: II.
463
H
R
dispersions in mineral oil, KBr pellets, and solutions in
carbon tetrachloride), as well as their 1H and 13C NMR
and mass spectra (Tables 1, 2; see Experimental). The
spectral parameters of compounds I–III allowed us to
conclude that, like other alkylsulfanyl-1,2,4-triazoles
[1], only one tautomer is present in the crystalline and
gaseous phases and in solution, except for solutions in
trifluoroacetic acid where signals from two forms were
observed. However, it was difficult to choose between
six most favorable structures (I–III)a–(I–III)f was
difficult. Furthermore, unlike tautomers Ia–IIIa and
Ib–IIIb with a weakly acidic hydroxy group,
structures Ie–IIIe and If–IIIf could give rise to
autoprotonation of the triazole ring by the sulfanyl
group (structure like J).
N
N
SH
N
N
H
OH
Cl
N
OH
NaOH
R
S
N
I_III
R = H (I), Me (II), Ph (III).
With a view to obtain additional information, we
recorded the IR spectra of triazoles I–III (from films,
____________
H
H
OH
OH
N
N
H
N
N
S
N
N
R
N
N
O
S
S
N
R
R
H
Ia_IIIa
Ib_IIIb
Ic_IIIc
H
H
N
O
H
H
R
N
N
N
N
N
N
R
R
SH
SH
S
N
O
N
O
Id_IIId
Ie_IIIe
If_IIIf
____________
A high probability for formation of strong intra-
and intermolecular hydrogen bonds (including those
with participation of solvent molecules), as well as for
tautomeric and various exchange processes, requires
additional arguments for the choice of preferential
tautomer. For example, the IR spectra of triazoles I–III
(films and crystalline samples) contain strong
absorption bands in the frequency region below 2700
cm–1. These bands may be attributed to strong
hydrogen bonds of different kinds in tautomers a, b, d,
and f or NH···N hydrogen bonds in cyclic structures c
and d, taking into account that an analogous pattern is
intrinsic to the IR spectra of 5-substituted 3-
butylsulfanyl-1H-1,2,4-triazoles [1]. On the other
hand, the contribution of sulfanyl groups in tautomers
Ie–IIIe and If–IIIf cannot be ruled out, provided that
such tautomers exist. In the IR spectra of triazoles I–
III, recorded from solutions in carbon tetrachloride (c ≈
10–4 M), we observed absorption bands above 2500
cm–1 only at 3457(1) and 3300(1) cm–1, which are
typical of stretching vibrations of OH and NH groups
in the triazole ring (cf. [1]). Therefore, structures Ie–
IIIe and If–IIIf having free sulfanyl fragments can be
excluded. This conclusion is consistent with the mass
spectrometric data.
In the mass spectra of compounds I and II, the
relative intensity of the molecular ion peaks [M]+· is 9
and 7%, respectively. The intensity of the molecular
ion peak of triazole III increases to 15% due to
stabilizing effect of the phenyl group. In the region
corresponding to large m/z values, which provides the
most valuable information on the molecular structure,
all compounds displayed peaks from fragment ions
formed by elimination of hydroxy group from [M]+·.
Despite low intensity (~3%), the presence of the above
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

464
BUZYKIN et al.
Table 1. Proton chemical shifts (δ, ppm) and 1H–1H spin–spin coupling constants (JHH, Hz) in the 1H NMR spectra of 5-R-3-
(2-hydroxyethylsulfanyl)-1H-1,2,4-triazoles I–III and their salts
Comp.
Solvent
Structure
SCH2, t
CH2O, t
3JHH
5-R
Ratio A : B
no.
CD3OD, 25°C
CD3OD, 50°C
DMSO-d6
3.24
3.24
3.27
2.81
2.65
2.82
2.64
2.80
3.75
3.73
3.72
3.85
3.33
3.86
3.33
3.84
6.64
6.64
6.16
5.92
4.64
5.95
5.31
5.78
8.30 s
8.25 s
8.36
1:0
1:0
I
А
А
А
А
В
А
В
А
1:0
I
I
CF3COOH, 25°C
8.45 s
8.16 s
8.37 s
8.08 s
8.43 s
1.0:0.8
CF3COOH, 55°C
CF3COOH
11:1
I
Iа
4.4:1.0
2.63
2.49
3.29
3.45
5.32
5.41
8.15 s
В
В
c
93% H2SO4
CD3OD
7.94 db
–
I
3.14
3.22
3.32
3.08
3.04
3.75
3.82
3.79
3.61
4.15
6.39
6.13
6.58
6.44
5.68
2.36 s
2.38 s
2.40
II
II
II
II
II
А
А
А
А
А
Acetone-d6
CD3CN
1:0
1:0
1:0
1:0
DMSO-d6
CF3COOH
2.31 s
2.18 s
d
HCCl3
3.23d
3.24
2.90
4.06d
3.71
3.97
–
9.91 m, 7.38 m
7.97 m, 7.47 me
1:0
1:0
III
III
III
А
А
А
DMSO-d6
CF3COOH
6.44
5.89
f
–
1.4:1.0
2.76
2.55
3.38
3.50
5.35
5.40
7.16 mg
6.70 dh
В
А
H2SO4
10:1
III
g
2.76
3.23
3.64
3.73
-
–
В
А
D2O
5.92
8.72 s
1:0
IV
DMSO-d6
3.13
2.94
2.67
3.61
3.91
3.37
6.27
5.92
5.33
8.31 s
8.67 s
8.23 s
1:0
IV
IV
А
А
В
CF3COOH
1.4:1.0
a
Isolated from oxalate IV. b Doublet, 3JHH = 6.48 Hz. cApart from the major tautomer, no less than four minor forms were present.
d
e
3
3
Broadened singlet. Unresolved multiplet. f Ph (A): 7.10 d (2H, J = 8.58 Hz), 6.93 t (1H), 6.82 t (2H, J = 7.84 Hz). g Overlapped
signals. h Ph (A): 6.70 d (2H, 3J = 7.27 Hz), 6.64 t (1H, 3J = 7.58 Hz), 6.51 t (2H, 3J = 7.84 Hz).
ion peaks is quite characteristic, for molecules I–III
contain a hydroxyethylsulfanyl group. Elimination of
hydrogen atom from the molecular ion gives [M – H]+
ion which then lose water molecule. Unlike 1,5-
dihydro-1,2,4-triazole-5-thiones [25], the main
fragmentation pathway of the molecular ions derived
from compounds I–III involves cleavage of bonds in
the hydroxyethylsulfanyl group in the β- and γ-
positions with respect to the triazole ring. It should be
noted that most ions are formed as a result of
rearrangement processes with elimination of neutral
formaldehyde and acetaldehyde molecules and
migration of hydrogen to the charged fragment. Simple
bond dissociation in the substituent chain is
considerably less probable (see Experimental). In
contrast to 1,5-dihydro-1,2,4-triazole-5-thiones [25],
no nitriles were detected among the decomposition
products of compounds III. The general fragmentation
pathways of the molecular ions of triazoles I–III are
shown in the following scheme.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

TAUTOMERISM OF AZA CYCLES: II.
465
M+
H
m/z 144 (2%)
m/z 158 (2%)
m/z 220 (2%)
m/z 126 (8%)
m/z 140 (7%)
m/z 202 (5%)
R = H
R = CH3
R = Ph
N N
N
γ
β
_H
_H2O
OH
R
S
m/z 101 (100%)
m/z 115 (99%)
m/z 177 (95%)
m/z 115 (99%)
m/z 129 (100%)
m/z 191 (98%)
m/z 128 (3%)
m/z 142 (3%)
m/z 204 (2%)
R = H
R = CH3
R = Ph
1
As a rule, the H NMR spectra of triazoles I–III
contain signals only from protons in the ethylene
fragment and substituent in position 5 of the triazole
ring (Table 1), whereas signals from OH and NH
protons are rarely observed because of exchange
processes. For example, signals at δ 4.33 and 12.56
ppm were present in the spectrum of triazole II in
acetone-d6. However, the structure of preferential
tautomer cannot be determined on the basis of the
chemical shifts of protons in the CH2S and CH2O
groups and 5-substituent, even if we take into account
relevant data for model compounds (cf. [1, 26, 27]).
signals from sp3-hybridized methylene carbon atoms.
No signal from the sp3-hybridized C3 atom in spiro
tautomers Ic–IIIc and Id–IIId was detected.
According to the calculations, this signal should appear
at δC 100–125 ppm. In the spectra of dihydro-1H-
1,2,4-triazole derivatives having no electron-with-
drawing groups on Csp , the corresponding signal
3
should be located even in a stronger field. For
example, the chemical shift of C5 in the 13C NMR
spectra
of
1,4-diacetyl-3-acetylamino-5-aryl-4,5-
dihydro-1H-1,2,4-triazoles is 70 to 76 ppm, while sp2-
hybridized carbon atoms resonate at δC 140.2–
142.8 ppm [29]. The fact that the spectra of triazoles I–
III sometimes lack signals from one or both carbon
atoms in the triazole ring may be attributed to some
fast dynamic processes, including those with
participation of cyclic tautomers.
Signals from the C3 and C5 atoms in the triazole
ring of compounds I–III are often lacking in the 13C
NMR spectra recorded from solutions in neutral
solvents. For example, prolonged acquisition (several
days) is necessary to detect C3 and C5 signals in the
spectra of solutions in CD3OD. The chemical shifts of
C3 and C5 range from 154 to 159 and from 143 to 156
ppm, respectively (Table 2), i.e., they are typical of
other 1,2,4-triazole derivatives [26, 28]. The upfield
region of the 13C NMR spectra contains only two
These findings, though ambiguously, allowed us to
rule out cyclic structures Ic–IIIc and Id–IIId in
neutral solutions. In most cases, the 13C NMR spectra
2
displayed JHNC spin–spin coupling for neither C3 nor
C5 atom; such coupling would be useful to distinguish
Table 2. 13C chemical shifts (δC, ppm) and 13C–1H spin–spin coupling constants (JCH, Hz) in the 13C NMR spectra of 5-R-3-
(2-hydroxyethylsulfanyl)-1H-1,2,4-triazoles I–III
CH2S (t)
Bd
C3
C5
5-R
Comp.
no.
Solvent
Structure
δC
1JCH
δC
1JCH
δC
δC
1JCH
δC
–
CD3OD
–
–
35.57
35.61
30.77
141.40
141.12
145.75
61.73
61.74
61.98
144.45 157.71а 147.78 d 210.06
I
I
DMSO-d6
CF3COOH
144.72 157.09
146.84 155.16
147.78 209.33
142.37 227.27
–
A
–
I
A<B
B
35.07
142.57
65.95
155.47 154.49
142.60 225.81
–
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

466
BUZYKIN et al.
Table 2. (Contd.)
CH2S (t)
CH2O (t)
C3
δC
156.88c
C5
5-R
Comp.
Solvent
no.
Structure
δC
1JCH
δC
1JCH
δC
1JCH
δC
Ib
CF3COOH
33.14
145.24
68.46
146.78
–
–
–
A
A≈B
37.43
31.86
143.14
146.05
64.39
70.62
155.58 157.55c
145.24
225.95
228.89
B
A
–
Ib
95% H2SO4
155.49 154.65 m 143.10
–
A>B
Bd
–
32.63
34.49
32.36
142.42
140.97
145.46
–
–
–
144.87
146.74
228.88
209.27
–
–
IVe DMSO-d6
60.54
67.64
143.14 156.71
IVf CF3COOH
A>B
154.36 156.17 m 144.36 d 227.33
147.95 156.65 m 144.55g 226.79
A
36.63
31.39
144.50
145.68
63.38
66.53
–
–
B
IVh CF3COOH
A>>B
154.25 155.63 m 143.26
227.23
А
–
–
–
–
155.00
143.72
156.3i
225.01
–
–
В
–
–
–
–
CD3OD
35.49
145.03
62.34
143.91 156.3i
11.82 q (1J 116.03)
12.81 q (1J 128.60)
12.10 q (1J 130.45)
9.82 q (1J 134.42)
II
Acetone-d6
35.69q 140.95 63.01q 143.32 159.61 tk 156.56 q 3J 7.24
II
DMSO-d6
34.22
31.21
–
60.03
66.67
–
–
–
–
II
CF3COOH
144.96
154.04 155.15 tl 155.48 q 3J 7.27
1J 134.42
II
CDCl3
–
–
35.88
35.81
154.68
141.67
63.37
62.46
143.80
–
–
–
126.43 (Cm, 1J 160.33),
129.11 (Cо, 1J 166.96), 130.48
(Cp, 1J 164.47), Ci not found
126.07 (Ci), 127.07 (Cm, 1J
III
CD3CN
144.21
–
–
–
III
2
161.31, J 6.54), 129.82 (Cо,
2
1J 161.30., J 27.65), 131.15
(Cp, 1J 161.30, 2J 6.54)
CF3COOH
31.16
40.54
32.07
144.84
152.04
144.27
66.55
68.66
70.86
153.70 156.72
152.58 157.15
155.16 t 6.63
154.03 t 6.08
119.38 t (Ci, J 8.85), 128.20
(Cm, 1J 161.98, 2J 6.64),
131.06 (Cо, 1J 166.13, 2J 7.74),
136.02 (Cp, 1J168.67, 2J 7.18)
119.20 (Ci), 129.59 (Cm, 1J
III
A
B
–
2
160.88, J 7.74), 130.93 (Cо,
1J 165.86, 2J 7.18), Cp not
found
1
95% H2SO4
155.14 155.31 ti 155.22 t 4.27
117.60 m (Ci), 128.94 (Cm, J
III
163.4, 2J 7.51), 130.85 (Cо, 1J
166.72, J 7.27), 136.02 (Cp,
2
1J 164.94, 2J 7.51)
a
Multiplet including at least five lines, Δν = 5.17, 5.09, 6.01 Hz. b Triazole I isolated from oxalate IV contained traces of oxalic acid; δ
(HOCOCOOH) 161.36 ppm, q. c Quartet, J = 7.25 Hz. d The amount of the minor structure was small, and many signals from it were not
observed. e δC(HOOCCOO–)161.14 (J = 61.40 Hz), 165.80 ppm. f Not crystallized, δ(HOCOCOOH) 161.36 ppm, q. g The spectrum was
recorded in 4 days after dissolution, δ(HOCOCOOH) = 161.36 ppm, q. hDoublet of doublets, 3J = 23.18 Hz. i Weak signal. j Triplet of
triplets; CH2S, 3J = 2.24 Hz; CH2O, 3J = 3.86 Hz. k 3J = 4.66 Hz. l 3J = 6.95 Hz. m J = 5.98 Hz.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

TAUTOMERISM OF AZA CYCLES: II.
467
1
The H and 13C NMR spectra of salts IV and V in
trifluoroacetic acid differed from the spectra of the free
bases only by the A/B ratio (Tables 1, 2), though the
spectral pattern of the salts in the region corresponding
to carbon atoms in the triazole ring was sometimes
1H- and 2H-tautomers Ia–IIIa and Ib–IIIb. Only in
the 13C NMR spectrum of triazole I in CD3COD,
recorded without decoupling from protons, we
observed a signal from the C3 atom at δ 157.71 ppm as
a multiplet including no less than 5 lines. The
multiplicity of that signal indicates interaction not only
with the SCH2 protons but also with 5-H or NH.
Taking into account the above data and our previous
conclusions [1] we believe that structure a is preferred
to b and assigned triazoles I–III in crystal and neutral
solutions the structure of 1H-tautomers, i.e., 5-
1
13
more distinct. The H and C NMR spectra of oxalate
IV in D2O and DMSO-d6 almost coincided with the
spectra of triazole I in CD3OD and DMSO-d6,
respectively. Analogous patterns were observed for the
triazole III–hydrochloride V couple in DMSO-d6. The
spectra of triazoles I–III and salts IV and V in
concentrated sulfuric acid indicated mainly the
presence of one form (Tables 1, 2); in some cases,
small amounts of two and more species were detected;
presumably, these impurities are products of some
transformations. We presumed that solutions of
triazoles I–III in trifluoroacetic acid contain mixture
of the free bases and protonated forms. Compounds I–
III are likely to possess a weak basicity, and they
undergo complete protonation only in concentrated
sulfuric acid. The larger concentration of unprotonated
phenyltriazole III in H2SO4 as compared to triazole I
is very consistent with the above assumption.
Introduction of a phenyl group into the triazole
molecule reduces its basicity, and the fraction of
unprotonated molecules increases. Dissolution of salts
IV and V (as well as of other salts derived from a
weak base and a strong acid) in water, alcohols, and
DMSO is accompanied by almost complete hydrolysis,
which is responsible for the observed spectral patterns
(Tables 1, 2).
substituted
azoles.
3-(2-hydroxyethylsulfanyl)-1H-1,2,4-tri-
The choice of the structure of predominant
1
tautomer was hindered by the fact that the H and 13C
NMR spectra of triazoles I–III in trifluoroacetic acid
always contained signals from two forms. Initially, we
supposed the presence of two tautomeric triazolium
ions [30], as was reported for protonation of 1-methyl-
1,2,4-triazole [28] and other azoles (1,2,3-triazoles,
1,3,4-oxadiazoles, and tetrazoles) [31]. Signals from
the C3 and C5 atoms of triazoles I–III in trifluoroacetic
acid were located in the region typical of 1,2,4-
triazolium cations (Table 2) [28, 32, 33]. As might be
expected, protonation of the triazole ring in I–III leads
to upfield displacement of the C3 and C5 signals (δC
157–158 and 142–144 ppm for 5-fluoroalkyl-1,2,4-
trimethyl-1,2,4-triazolium salts [32] and 154–149 and
140–138 ppm for 4-alkyl-5-amino-1-(pyridiniome-
thyl)-1,2,4-triazolium chlorides [33]).
The species observed in trifluoroacetic acid were
arbitrarily denoted as A and B, and their ratio
depended on the method of purification and conditions
of NMR experiments, including the time elapsed after
dissolution. The upfield CH2S carbon signal was
assumed to belong to structure A. The A-to-B ratios
(Tables 1, 2) were estimated from the intensities of pro-
ton and carbon signals of the CH2S and CH2O groups.
1,2,4-Triazolium salts continuously attract rese-
archers’ attention [19, 20, 28, 32, 34, 35]. In the recent
years, some 1,2,4-triazolium salts were shown to
inhibit corrosion of copper [36] and iron [37] and act
as ionic liquids [32, 38]. 3-Amino-1,2,4-triazolium
salts are used in agriculture (e.g., Amitrole) and
organic synthesis, as well as individual explosives and
components of rocket fuels and emulsion explosives
[19, 20, 23, 39]. However, the structure of 1,2,4-
triazolium salts (as well as of salts derived from other
heterocyclic systems) was studied to a considerably
lesser extent than the structure of initial heterocycles,
although most practically important 1,2,4-triazole
derivatives are used just as salts. A few studies were
performed on triazolium salts having no substituent on
the nitrogen, their protonation, and charge localization,
though these problems have long attracted attention,
specifically of chemists working in the field of 3-
amino-1,2,4-triazoles [34, 35]. The main reasons for
such situation in the azole chemistry are related to
We prepared a series of salts from triazoles I–III.
Hydrochlorides and hydrobromides derived from
triazoles I and II turned out to be very hygroscopic,
and we failed to isolate these salts as crystalline
substances. Crystals suitable for X-ray analysis were
obtained only from triazole I oxalate (salt IV) and
triazole III hydrochloride (V). The isolation of
triazoles I–III from the corresponding salts also
involved strong difficulties. For example, we did not
succeed in completely removing oxalic acid from
oxalate IV, and its traces were detected in the spectra
of triazole I isolated from IV.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

468
BUZYKIN et al.
difficulties arising from limited solubility of triazolium
salts and inevitability of exchange processes; in
addition, potential tautomerism of NH-triazolium salts
strongly restricts the choice of subjects for study [28].
The IR and 1H and 13C NMR spectral data obtained
in this work were insufficient to unambiguously
determine the structure of protonated forms of triazoles
I–III; the most probable structures are shown below.
Taking into account the above conclusions
excluding spirocyclic and thiol structures (I–III)c–(I–
III)f, the formation of the corresponding protonated
species may also be ruled out, though such structures
may sometimes be more stable than open-chain
tautomers. Furthermore, protonation of triazoles I–III
may be accompanied by change of the position of
hydrogen atoms. For instance, the 13C NMR spectra of
salts IV and V sometimes revealed additional
couplings for the C3 and C5 atoms in those species
which were assumed to bear a positive charge (Table
2). Insofar as no spin–spin coupling with the NH
hydrogen atom was observed for C3 and C5 in neutral
triazole molecules, the observed spectral patterns are
fairly difficult to interpret.
H
H
OH
OH
OH
OH
H
H
N+
N
N
+
N
N
N
S
S
N
R
R
IVa, Va
IVb, Vb
With a view to determine the structure of
protonated forms of triazoles I–III, oxalate IV and
hydrochloride V were studied by the X-ray diffraction
method. Suitable single crystals were grown from
aqueous methanol. Figure 1 shows the structure of the
cationic and anionic fragments of oxalate IV. The
asymmetric part of a unit cell includes two cation–
anion couples where cations IVA and IVB differ in the
H
N
H
N
N
S
S
+
+
N
N
R
R
H
H
IVc, Vc
IVd, Vd
O10A
C8A
O12A
O8B
N1B
C5B
C9A
O9A
O8A
C7A
C7B
N2B
C3B
C6B
O11A
N4B
N1A
N2A
C3A
C6A
S3B
C5A
N4A
O11B
C9B
O12B
O9B
S3A
C8B
O10B
Fig. 1. Structure of cations IVA and IVB and oxalic acid monoanions in 3-(2-hydroxyethylsulfanyl)-1H,4H-1,2,4-triazolium
hydrogen oxalate (IV) in crystal according to the X-ray diffraction data. Cation IVA with larger population of the disordered
hydroxyethyl fragment is shown.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

TAUTOMERISM OF AZA CYCLES: II.
469
Table 3. Bond lengths (d, Å) in the triazole ring of N-unsubstituted and substituted 1,2,4-triazolium salts IV–XXIII
+
R1
N N
R5
R3
N
R4
Comp.
no.
R1
R3
R4
R5
K+Cа
K+Aа
N1–N2
N1–C5
N2–C3
N4–C3
N4–C5 Reference
b
H
H
H
H
H
H
H
H
H
H
H
H
SCH2CH2OH
H
H
H
H
H
H
H
H
H
H
H
H
H
H
–
1,4+-C
1.36(1)
1.29(1)
1.31(2)
1.34(1)
1.32(1)
1.33(1)
1.34(1)
–
–
–
IVA
b
b
SCH2CH2OH
–
1,4+-C 1.375(8) 1.28(1) 1.287(9) 1.35(1)
1,4+-C 1.387(9) 1.34(1)
1.29(1) 1.39(1)
1+,2-C 1.363(2) 1.307(2) 1.295(2) 1.349(2) 1.321(3)
1,4+-C
[Tr]+
1,4+-C 1.377(3) 1.321(3) 1.288(3) 1.361(3) 1.343(3)
1,4+-C 1.382e
1.328 1.293 1.368 1.340
1,4+-C 1.386(5) 1.326(5) 1.295(6) 1.366(7) 1.349(5)
1,4+-C
1,4+-C
IVB
SCH2CH2OH
Ph
–
V
VIc
VIId
VIIIf
IXg
Xh
XIi
XIIj
XIIIk
XIVl
H
H
H
H
H
H
H
H
H
H
1+,4-C
1,4+-C
1+,4-C
1,4+-C
1,4+-C
1+,4-C
1,4+-C
1,4+-C
1,4+-C
[43]
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
H
1.343e
1.365(2) 1.309(2) 1.302(2) 1.356(2) 1.332(2)
1.313
1.289
1.368
1.327
H
NH2
NH2
NH2
NH2
NH2
NH2
1.374e
1.387e
1.322
1.330
1.286
1.291
1.356
1.363
1.338
1.343
1,4+-C 1.388(3) 1.329(3) 1.291(4) 1.367(4) 1.347(3)
XVm
XVIn
H
H
H
H
H
H
NH2
NH2
1,4+-C
1,4+-C
1,4+-C 1.368(3) 1.330(3) 1.290(3) 1.349(3) 1.342(3)
1,4+-C 1.375(5) 1.316(6) 1.282(6) 1.346(7) 1.361(6)
[52]
[52]
XVIIo
XVIIIp
XIXq
H
Me
H
HN–NH3+
C8F17
Et
H
NH2
Me
Et
1,4+-C
1,4+-C
1,4+-C
[Tr]+
[Tr]+
1,4+-C
1.397(6) 1.322(6) 1.291(6) 1.363(6) 1.352(6)
[53]
[32]
[54]
Me
NH2
1.353e
1.327
1.296
1.303
1.310
1.368
1.379
1.340
1.316
1.365e
XXr
XXIf
XXIIf
XXIIIr CH2Ru
H
H
NH2
Me
NH2
NH2 NHRt
Art
NH2
1+,4-C
1+,4-C
1,4+-C
–
1+,4-C 1.408(5) 1.311(5) 1.298(5) 1.382(5) 1.343(5)
[55]
[56]
[57]
[23]
–
–
–
1.378e
1.385e
1.39e
1.326
1.315
1.31
1.300
1.323
1.33
1.378
1.400
1.36
1.343
1.353
1.32
Me
NMe2
H
NMe2
H
NH2
1+,4-C
1.376
1.371
1.317
1.334
1.297
1.317
1.365
1.355
1.338
1.327
Average value
Average value for neutral analogsv
[1]
a
1+,4-C stands for positive charge localization on the N1 atom of the triazole ring, 1,4+-C denotes charge localization on the N4 atom, and
[Tr]+ stands for delocalization of the positive charge over the triazole ring according to the CSD [C+(C)] and authors’ data [C+(A)].
b
c
d
This work.
Bis(methanesulfonyl)amidate.
Perchlorate; the dihydro-1,2,4-triazolium cation forms a host–guest complex with
dibenzocrown-6. e No standard deviations for bond lengths and bond angles were given. f Chloride. g 3-Nitrobenzoate. h Thiophene-2-
carboxylate. i 4-Nitrobenzoate. j 5-Nitrofuran-2-carboxylate. k Pyrazinedicarboxylic acid monoanion. l 3-Nitro-1,2,4-triazol-5-olate.
m
n
o
p
–
q
r
s
2-Hydroxy-5-nitrobenzoate. 2-Hydroxy-3,5-dinitrobenzoate. Two chloride ions. BF4 . [(NC)2Au]–. Bromide. R = 2,6-
u
Cl2C6H3CH=N. t Ar = 2-HOC6H4. R = 2-(4-amino-1,2,4-triazol-1-io)methyl bromide. v Average values for neutral 1H-mono-, 1H-3,5-
di-, and 1,3,5-trisubstituted 1,2,4-triazoles according to [1].
geometric parameters of the hydroxyethylsulfanyl
fragment. The latter in cation IVA is disordered by two
positions with populations of 0.58 and 0.42. The major
fragment has the same geometric parameters of the
hydroxyethylsulfanyl group as in cation IVB. The
geometric parameters of the heterorings in both cations
are similar (Tables 3, 4), and the torsion angles in
cation IVA refer to the fragment with the larger
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

470
BUZYKIN et al.
Table 4. Bond angles (ω, deg) in the triazole ring of N-unsubstituted and substituted 1,2,4-triazolium salts IV–XXIII (for
anions and references, see Table 3)
+
R1
N N
R5
R3
N
R4
Comp.
no.
R1
R3
R4
R5
K+Cа
K+Aа
N2N1C5
N1N2C3
C3N4C5
N2C3N4
N4C5N1
H
H
H
H
H
H
SCH2CH2OH
H
H
H
H
H
H
H
H
–
1,4+-C
1,4+-C
1,4+-C
1+,2-C
1,4+-C
[Tr]+
111.9(8) 102.1(7)
111.3(3) 103.6(7)
112.2(7) 102.5(7)
110.9(2) 103.8(1)
105.8(8)
106.0(8)
105.4(7)
106.5(2)
106.4
112.4(7)
111.5(8)
113.5(7)
111.5(2)
110.5
107.8(9)
107.7(9)
106.5(7)
107.2(2)
106.5
IVА
SCH2CH2OH
–
IVC
V
SCH2CH2OH
Ph
H
–
H
H
H
1+,4-C
1,4+-C
1+,4-C
VI
H
111.5b
104.9
VII
VIII
H
111.7(1) 103.5(1)
111.5(2) 103.2(2)
106.5(2)
111.5(2)
106.7(2)
H
H
H
H
H
H
H
H
H
NH2
NH2
NH2
1,4+-C
1,4+-C
1+,4-C
1,4+-C
1,4+-C
1,4+-C
105.8(2)
106.6
112.9(2)
112.0
106.5(2)
106.4
IX
X
111.2b
112.4(3) 102.7(4)
103.8
106.6(4)
112.8(4)
105.5(3)
XI
H
H
H
H
H
H
H
H
H
NH2
NH2
NH2
1,4+-C
1,4+-C
1,4+-C
1,4+-C
1,4+-C
1,4+-C
111.4b
111.3b
103.4
103.7
106.2
112.7
106.3
XII
107.0
112.1
105.9
XIII
XIV
111.8(2) 103.3(2)
111.6(2) 103.2(2)
112.0(4) 103.6(4)
111.5(4) 102.6(4)
106.8(2)
112.4(2)
105.7(2)
H
H
H
H
H
H
H
H
NH2
NH2
NH2
1,4+-C
1,4+-C
1,4+-C
1,4+-C
1,4+-C
[Tr]+
106.2(2)
106.5(4)
105.7(4)
113.0(2)
112.7(4)
113.6(4)
105.9(2)
105.2(4)
106.6(4)
XV
XVI
XVII
+
HN–NH3
Me
H
C8F17
Et
Me
Me
Et
1,4+-C
1,4+-C
[Tr]+
112.0b
114.0b
103.8
101.8
105.8
106.6
111.9
111.3
106.5
106.3
XVIII
XIX
NH2
1,4+-C
H
H
NH2
Me
NH2
NH2
NH2
1+,4-C
1+,4-C
–
111.4(4) 103.8(4)
107.1(4)
107.9
110.0(4)
110.0
106.7(4)
105.7
XX
NHRc 1+,4-C
NMe2 1,4+-C
111.5b
105.0
XXI
Me
NMe2
H
Ard
–
112.6b
110.6b
103.8
103.5
106.5
107.7
110.4
110.1
106.7
108.2
XXII
CH2Re
NH2
H
–
1+,4-C
XXIII
Average value
111.7
110.3
103.4
101.6
107.7
101.7
111.8
114.9
106.5
110.6
Average value for neutral analogsf
a
1+,4-K stands for positive charge localization on the N1 atom of the triazole ring, 1,4+-C denotes charge localization on the N4 atom, and
[Tr]+ stands for delocalization of the positive charge over the triazole ring according to the CSD [C+(C)] and authors’ data [C+(A)].
b No standard deviations for bond lengths and bond angles were given. c R = 2,6-Cl2C6H3CH=N. d Ar = 2-HOC6H4. e R = 2-(4-amino-
1,2,4-triazol-1-io)methyl bromide. f Average values for neutral 1H-mono-, 1H-3,5-di-, and 1,3,5-trisubstituted 1,2,4-triazoles according
to [1].
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TAUTOMERISM OF AZA CYCLES: II.
471
Fig. 2. Hydrogen bond system in 3-(2-hydroxyethylsulfanyl)-1H,4H-1,2,4-triazolium hydrogen oxalate (IV) in crystal. A layer of
molecules formed via hydrogen bonding (dashed lines) is shown.
population (0.58; Table 5).
phenyl-1H,4H-1,2,4-triazolium chloride] and one
water molecule. The bond lengths and bond angles
therein are given in Tables 3 and 4. Unlike cations IVA
and IVB, the cation in salt V contains a phenyl group
and is characterized by a different conformation with
respect to the C6–C7 bond. The torsion angle S3C6C7O8
in that cation is equal to 60.7(9)° against 178.7(1) and
175.6(7)° in IVA and IVC, respectively (Table 5). The
triazole ring in V is planar, and the dihedral angle
Both anionic species in salt IV are oxalic acid
monoanions linked to 10-membered cyclic dimers by
two O–H···O hydrogen bonds (Fig. 2). These H-
dimers are involved in a complex system of
intermolecular hydrogen bonds with cations IVA and
IVB, giving rise to alternation of positively and
negatively charged fragments in the crystalline
structure of oxalate IV (Fig. 2). An analogous
hydrogen bond motif formed by oxalic acid
monoanion (denoted in [40] as B) together with chain-
like motif A and motif C formed by isolated hydrogen
oxalate ion was described for alkylammonium
oxalates, while oxalates derived from α-amino acids
contained oxalate dianion [41]. Hydrogen bonds
between molecules IV in crystal also produce a two-
dimensional supramolecular structure, a layer parallel
to the (101) crystallographic plane.
Table 5. Some torsion angles (φ, deg) in the cationic parts of
oxalate IV and hydrochloride V
Angle
Vа
IVА
IVВ
N2C3S3C6
N4C3S3C6
C3S3C6C7
S3C6C7O8
–28(1)
151.8(9)
85(1)
1(1)
1.3(9)
–179.3(7)
73.7(7)
179.0(8)
75.8(8)
176.1(7)
177(1)
60.7(9)
The asymmetric part of a unit cell of hydrochloride
V monohydrate in crystal (Fig. 3) consists of one
cation–anion couple [3-(2-hydroxyethylsulfanyl)-5-
a
N1C5C9C10 –6(1); N4C5C9C10 171.4(8); N1C5C9C14 174.3(8);
N4C5C9C14 –8(1).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

472
BUZYKIN et al.
Crystallographic Data Center [42]. It turned out that
Cl1
the umber of 1,2,4-triazolium salts studied by X-ray
diffraction is lesser by an order of magnitude than the
number of neutral 1,2,4-triazole derivatives. We found
the data for three slats of parent 1,2,4-triazole with
different anions, ten salts derived from 5-amino-1,2,4-
triazole, and eight N-substituted 1,2,4-triazolium salts
(Tables 3, 4).
C14
C13
C12
N4
C5
O8
S3
С6
C3
C9
C11
С7
N1
Comparison of the data for salts IV and V, neutral
1H-mono-, 1H-3,5-di-, and 1,3,5-trisubstituted 1,2,4-
triazoles [1], and 1,2,4-triazolium salts VI–XXIII [23,
32, 43–57] shows a weak effect of protonation on the
geometric parameters of the 1,2,4-triazole ring [1, 23,
32, 43–57] (Tables 3, 4). The cations in salts IV and V
retain bond length alternation and clearly display
conjugation effect, especially in the N1C5N4 amidine
fragment of hydrochloride V (Table 3). Analysis of the
bond lengths in IV and V and in particular groups of
neutral 1,2,4-triazoles [1] does not allow us to
determine the protonation center and charge
localization in the former. Insofar as the NH hydrogen
atoms in the cationic species of IV and V were
localized from difference series of electron density, we
can conclude (Figs. 1, 3) that one hydrogen atom is
attached to N1 and that acidic proton adds at the
nitrogen atom in position 4 of the triazole ring. This
conclusion is consistent with the X-ray diffraction data
for a series of 1,2,4-triazolium salts [23, 32, 43–57],
N2
C10
O15
Fig. 3. Structure of 3-(2-hydroxyethylsulfanyl)-5-phenyl-
1H,4H-1,2,4-triazolium chloride monohydrate (V) in crystal
according to the X-ray diffraction data (independent part of a
unit cell is shown).
between the triazole and benzene ring planes is 7.8
(4)°. The cation and anion of salt V and water
molecule in crystal give rise to three-dimensional
supramolecular structure (Fig. 4); the hydrogen bond
parameters are collected in Table 6. In addition, one C–
H···N intramolecular contact was revealed (Table 6).
As previously [1], we performed comparative
analysis using the data from the Cambridge
Fig. 4. Packing of 3-(2-hydroxyethylsulfanyl)-5-phenyl-1H,4H-1,2,4-triazolium chloride monohydrate (V) molecules in crystal and
hydrogen bond (dashed lines) system therein.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

TAUTOMERISM OF AZA CYCLES: II.
473
Table 6. Parameters of shortened contacts (Å, deg) in the crystalline structures of oxalate IV and hydrochloride V
D–H···A
D–H
H···A
D···A
∠DHA
Symmetry operation
3-(2-Hydroxyethylsulfanyl)-1H,4H-1,2,4-triazolium hydrogen oxalate (IV)
N1A–H1A···O8B
N1B–H1B···O8A
N4A–H4A···O9A
N4A–H4A···O11A
N4B–H4B···O9B
N4B–H4B···O11B
O8A–H8A···O10B
O8B–H8B···O10A
O12A–H12A···O10B
O12B–H12B···O10A
O12A–H12A···O10A
O12B–H12B···O10B
C5A–H5A···O11B
С5B–H5B···O11A
C6A–H62A···O9B
0.76(8)
0.86(8)
0.94(8)
0.94(8)
0.82(6)
0.82(6)
0.82
1.94(8)
1.83(8)
1.79(8)
2.36(7)
1.90(6)
2.42(6)
1.89
2.67(1)
2.65(1)
2.65(1)
2.95(1)
2.67(1)
2.95(1)
2.70(1)
2.686(9)
2.663(9)
2.660(9)
2.696(9)
2.70(1)
3.25(1)
3.24(1)
3.41(2)
162(8)
159(8)
151(7)
120(6)
158(6)
124(5)
170.9
169.3
145.9
145.0
115.8
114.0
162(9)
174(7)
145.5
1–x, 2–y, 1–z
1–x, 2–y, 1–z
–1+x, y, z
–1+x, y, z
1–x, 1–y, –z
1–x, 1–y, –z
x, y, 1+z
0.82
1.88
2–x, 1–y, 1–z
x, –1+y, z
x, 1+y, z
0.82
1.94
0.82
1.95
0.82
2.24
–
0.82
2.25
–
0.89(9)
0.84(7)
0.97
2.40(9)
2.40(7)
2.56
–1+x, y, z
1–x, 1–y, –z
x, y, 1+z
3-(2-Hydroxyethylsulfanyl)-5-phenyl-1H,4H-1,2,4-triazolium chloride monohydrate (V)
N1–H1···O15
N4–H4···Cl1
O8–H8···Cl1
O15–H151···Cl1
O15–H152···O8
C7–H71···N2
1.0(1)
1.7(1)
2.714(9)
2.945(8)
3.060(7)
3.134(7)
2.731(9)
3.25(1)
159(8)
172(6)
160(7)
173(6)
125(5)
128(9)
–
1.00(8)
0.81(7)
0.93(8)
0.51(5)
1.0(1)
1.96(8)
2.29(7)
2.21(8)
2.40(4)
2.6(1)
–
x, 3/2–y, 1/2+z
x, –1+y, z
1–x, –1/2+y, 1/2–z
–
given in Table 3. Unfortunately, most data refer to salts
derived from amino-substituted 1,2,4-triazoles
possessing even larger number of possible protonation
centers. These salts were previously assigned the
structure of iminium cations on the basis of only IR
data [34, 35].
The C3–S3 bond length in cations IVA, IVB, and V
is 1.741(9), 1.730(8), and 1.746(9) Å, respectively; i.e.,
it differs only slightly from the corresponding bond
length in neutral analogs of 3-alkylsulfanyl-1,2,4-
triazoles [1]. The C3–S3 bond is appreciably shorter
than the S3–C6 bond with the hydroxyethyl fragment
(1.77–1.79 Å) and is closer to standard single Csp2–S
bond (1.751 Å; cf. 1.671 Å for double Csp2=S bond
[58]). The C–C and C–O bond lengths in IVA, IVB,
and V approach those typical of hydroxyethyl groups
[58].
of the N1N2C3 angle are minimal (Table 4). These data
indicate that protonation affects the N1C5N4 fragment
to the greatest extent. Naturally, the character of
protonation-induced variations also depends on the
nature of substituents present in the molecule (Tables
3, 4). For example, bond length leveling in the
heteroring of hydrochloride V is on the whole less
pronounced than in oxalate IV but is stronger in the
amidine N1C5N4 fragment.
The average N2N1C5 angle in neutral triazoles is
110.3° [1]; the corresponding values for salts IVA,
IVB, and V are 111.9(8), 111.3(8), and 112.2(7)°,
respectively. The endocyclic bond angles at the N2, C3,
and C5 atoms also coincide within experimental error
with those found for their neutral analogs [1]. The
average C3N4C5 angle in neutral triazoles is
considerably smaller than in the triazolium cations in
salts IVA, IVB, and V and is 101.7° [IVA, 105.9(9)°;
IVB, 106.0(8)°; V, 105.4(7)°]. The corresponding
angle in other protonated triazoles (VI–XXIII) [23, 32,
Changes of the bond angles upon protonation of the
examined 1,2,4-triazoles are more appreciable. The
C3N4C5 angle changes most strongly, while variations
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

474
BUZYKIN et al.
43–57] is appreciably larger than in the free bases; it
ranges from 105.7(4) to 107(1)° (Table 4, cf. [1]).
density is localized just on the N4 atom [33, 59] (see
also references given in [1]). On the other hand, the
site of proton addition (N4) is not necessarily the site of
localization of the positive charge in the ring. Tables 3
and 4 contain sometimes contradictory views of
authors of the original articles and CSD compilers on
preferential structure of cationic species given therein.
The structures of cations IVe and Ve with probable
charge localizations are shown below.
Analysis of the data in Tables 3 and 4 led us to
conclude that 1,2,4-triazoles having no substituent on
the nitrogen atom and their 1-substituted analogs
always undergo protonation at the nitrogen atom in
position 4. This conclusion is consistent with the
results of theoretical calculations of 1,2,4-triazole
molecule, according to which the largest electron
____________
R1
R1
H
H
N N
N+ N
N
N N
N+ N
N
R5
R5
R5
R5
R3
R3
R3
R3
+
N
+
N
R4
R4
H
H
1,4+-C
1+,4-C
1,4+-C
1+,4-C
H
H
H
H
H
H
N N+
N
N N
N N+
N
N+ N
N
R5
R5
R5
R5
R3
R3
R3
R3
+
N
H
H
2+,4-C
2,4+-C
1,2+-C
1+,2-C
+
R1
N N
R5
R3
N
R4
____________
OH
The structures of 1,2,4-triazolium cations assumed
in [23, 32, 43–57] were substantiated insufficiently. In
some cases, cation structure was represented as a set of
canonical structures in terms of the resonance theory
[57] or as complete charge delocalization over the ring
[26], which are difficult to match with the
experimental data. We give preference to structures
IVc and Vc; however, taking into account bond length
alternation in the triazole ring and simultaneous bond
leveling in the amidine fragment, structures like IVe
and Ve with partial charge delocalization seem to be
the most probable.
H
R
N
N
S
+
N
H
IVe, Ve
and precise X-ray diffraction studies are likely to be
necessary to analyze electron density distribution in
1,2,4-triazolium cations.
EXPERIMENTAL
In order to draw a final conclusion on charge
localization in 1,2,4-triazolium cations IV and V and
other related systems, quantum-chemical calculations
The IR spectra were recorded on a UR-20
spectrometer from films, dispersions in mineral oil,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

TAUTOMERISM OF AZA CYCLES: II.
475
KBr pellets, and solutions in carbon tetrachloride (c ≈
ol was added until the mixture became homogeneous,
and the resulting solution was passed through a column
charged with aluminum oxide. The column was
additionally washed with a small amount of propan-2-
ol. The elueate were combined and evaporated under
reduced pressure, the residue was treated with
chloroform, and the crystals were filtered off, washed
with chloroform and a small amount of acetone, and
dried in air. Yield 9.6 g (49.4%), snow-white fine
1
13
10–4 M). The H and C NMR spectra were measured
1
on Bruker MSL-400 (400.13 MHz for H and 100
MHz for 13C) and Avance 600 spectrometers (600.00
MHz for 1H and 150.864 MHz for 13C) using
tetramethylsilane as internal reference or acetone-d6 as
external reference. The mass spectra (electron impact)
were obtained on a Trace MS GC–MS system (solvent
ethanol). The melting points were determined on a
Boetius type melting point apparatus or standard PTP crystals, mp 74–76°C (capillary, PTP), 77.5–79°C
(Boetius apparatus). IR spectrum, ν, cm–1: mineral oil:
instrument.
3128 v.br, 1556, 1333,1292, 1263, 1223, 1205, 1165,
2-(1H-1,2,4-Triazol-3-ylsulfanyl)ethanol (I). A
solution of 20.9 g of potassium hydroxide in 300 ml of
methanol was added to 27.82 g of 2,3-dihydro-1H-
1117, 1078, 1056, 1016, 950, 779, 719, 701; CCl4 (c ≈
10–4 M): 3457, 3300. Mass spectrum, m/z (Irel, %): [M]+·
159 (7), 158 (2), 142 (3), 140 (7), 129 (100), 128 (38),
1,2,4-triazole-3-thione, the mixture was heated for 30
116 (9), 115 (99), 114 (46), 99 (17), 96 (12), 84 (35),
min under reflux, 27.0 g of 2-chloroethanol was added,
74 (22), 59 (15), 58 (22), 57 (16), 56 (59), 46 (12), 45
and the mixture was heated for 3 h under reflux. The
1
(44), 43 (26), 42 (84). The H and 13C NMR spectra
mixture was cooled, the precipitate of potassium
are given in Tables 1 and 2. Found, %: C 37.67, 37.64;
chloride was filtered off, and the filtrate was
H 5.51, 5.49; N 26.53, 26.48; S 19.78, 19.86.
evaporated. The residue, 45 g, was a syrup-like
C5H9N3OS. Calculated, %: C 37.72; H 5.70; N 26.39;
material which was dissolved in propan-2-ol, and the
solution was passed through a column charged with
S 20.14.
aluminum oxide to remove residual KCl. After
prolonged evacuation, we obtained about 37 g (91%)
of a syrupy material which did not crystallize over
several months. After storage for more than a year, a
2-(5-Phenyl-1H-1,2,4-triazol-3-ylsulfanyl)ethanol
(III). A solution of 0.73 g of potassium hydroxide in
25 ml of methanol was added to 1.77 g of 5-phenyl-
1H-1,2,4-triazole-3-thiol, the mixture was heated for
few colorless crystals were formed, but we failed to
0.5 h, 0.98 g of 2-chloroethanol was added, and the
separate them from the oily material because of ready
mixture was heated for 3 h under reflux. The mixture
solubility in most organic solvents. IR spectrum, ν,
was cooled, the precipitate of potassium chloride was
filtered off, and the filtrate was evaporated under
reduced pressure. The residue was dissolved in 10 ml
of boiling methylene chloride, 15–20 ml of aluminum
oxide was added until a free-flowing material was
obtained, and the latter was placed into a separatory
cm–1: film: 3300 and 3100 v.br, 1646, 1514, 1277,
1242, 1178, 1067, 1046, 1014, 974; CCl4 (c ≈ 10–4 M):
3458, 3300. The 1H and 13C NMR spectra are given in
Tables 1 and 2. Mass spectrum, m/z (Irel, %): [M]+· 145
(9), 144 (2), 128 (3), 126 (8), 116 (7), 115 (99), 114
(46), 102 (14), 101 (100), 82 (10), 74 (17), 71 (13), 70
funnel and washed with 50 ml of methylene chloride.
(43), 60 (10), 46 (15), 45 (53), 44 (17), 43 (47), 42
The eluate was cooled, white crystals of triazole III,
0.1 g, were filtered off, and the filtrate was evaporated.
(36). Found, %: C 32.87, 32.94; H 4.56, 4.39; N 28.59,
29.68; S 21.78, 21.89. C4H7N3OS. Calculated, %: C
The residue, 0.7 g, was a thick syrupy material which
33.09; H 4.86; N 28.94; S 22.08.
crystallized in storage for 5 days. The crystalline
material was ground with a small amount of methylene
chloride, and the crystals were separated. We thus
isolated an additional 0.4 g of triazole III as white
crystals with mp 103–105°C (Boetius apparatus). The
overall yield of the pure product was 23%. The yield
may be considerably improved by repeating the
procedure for isolation from the mother liquor. IR
spectrum, ν, cm–1: KBr: 3210 and 3132 br, 3075, 2793,
2670, 1611 w, 1561, 1492, 1418, 1334, 1282, 1268,
1181, 1145, 1123, 1065, 1022, 1010, 980; mineral oil:
3210, 3131, 3074, 2750, 2660, next the same as in
2-(5-Methyl-1H-1,2,4-triazol-3-ylsulfanyl)etha-
nol (II). A solution of 4.2 g of sodium hydroxide in 8
ml of water was added under stirring to a suspension of
11.5 g of 5-methyl-2,3-dihydro-1H-1,2,4-triazole-3-
thione in 75 ml of propan-2-ol, the mixture was heated
until it became homogeneous, 10 ml of 2-
chloroethanol was added. and the mixture was heated
for 3 h under reflux and left overnight. The solvent
was removed under reduced pressure (water-jet pump)
on heating on a water bath, and the residue was treated
with chloroform (two layers were formed). Propan-2-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

476
BUZYKIN et al.
KBr. The 1H and 13C NMR spectra are given in Tables
1 and 2. Mass spectrum, m/z (Irel, %): [M]+· 221 (15),
220 (2), 204 (2), 202 (5), 192 (12), 191 (98), 190 (23),
178 (12), 177 (95), 161 (11), 158 (18), 146 (18), 119
(13), 118 (41), 104 (100), 103 (54), 91 (29), 77 (52),
76 (26), 74 (16), 63 (13), 51 (22), 45 (30), 43 (15).
Found, %: C 54.40, 54.35; H 4.91, 4.82; N 19.11,
19.06; S 14.02, 14.31. C10H11N3OS. Calculated, %:
C 54.28; H 5.01; N 18.99; S 14.49.
12.74; N 15.41,15.36; S 12.28, 12.31. C10H11N3OS·HCl·H2O.
Calculated, %: C 43.56; H 5.12; Cl 12.86; N 15.24;
S 11.63.
X-Ray analysis of triazolium salts IV and V.
Single crystals were obtained from solutions in
methanol–water (10:1). The X-ray diffraction data
were acquired at room temperature (20°C) on an
Enraf–Nonius CAD-4 automatic four-circle diffracto-
meter [monochromatized MoKα irradiation, λ =
0.71073 Å (IV), or CuKα irradiation, λ = 1.54184 Å
(V); graphite monochromator]. The unit cell
parameters were determined from 25 reflections. The
stability of crystals during data acquisition was
checked by measuring the intensities of three control
reflections every two hours, and orientation of the
crystals was monitored by centering two reflections
after every 200 reflections. No drop in the intensity of
control reflections was observed. The unit cell
parameters were determined, and preliminary
processing of the experimental data was performed,
using MolEN software [60]. The structures were
solved by the direct method using SIR program [61].
The structures were refined first in isotropic and then
in anisotropic approximation using MolEN software
[60] for compound V and SHELX-97 [62] from
WinGX [63] for compound IV. All structures were
plotted, and intermolecular interactions were analyzed,
using PLATON program [64]. The X-ray diffraction
experiments were performed at the X-Ray Analysis
Department (Collective Use Center, Spectral
Analytical Center, Laboratory of Diffraction Methods,
Arbuzov Institute of Organic and Physical Chemistry,
Kazan Research Center, Russian Academy of
Sciences).
3-(2-Hydroxyethylsulfanyl)-1H,4H-1,2,4-triazo-
lium hydrogen oxalate (IV). Crude syrupy triazole I,
45 g, was dissolved in 200 ml of ethanol, the solution
was filtered, and the filtrate was added to a hot
solution of 10 g of oxalic acid. The mixture was stirred
for 10 min and filtered while hot to remove potassium
oxalate which is almost insoluble in hot ethanol. An
additional amount of oxalic acid, 25 g, was added to
the filtrate, and the resulting solution was cooled in a
refrigerator. The crystals were filtered off, washed with
cold ethanol, and dried. Recrystallization from
methanol gave 31 g (42.5%) of salt IV as a white
crystalline powder with mp 138–140°C (PTP), which
is readily soluble in water, DMSO, and DMF. The
product melted at 132–136°C with partial
decomposition on a Boetius type hot stage. IR
spectrum (mineral oil), ν, cm–1: 3199, 3113, 2665,
2611, 1751, 1651, 1559, 1528, 1421, 1306, 1240,
1
1188, 1174, 1138, 1058, 1023, 946. The H and 13C
NMR spectra are given in Tables 1 and 2. Found, %: C
30.58; H 3.81; N 18.03; S 13.17. C4H7N3OS·C2H2O4.
Calculated, %: C 30.64; H 3.86; N 17.86; S 13.60.
Evaporation of the mother liquor to 1/4 of the initial
volume gave an additional amount of salt IV which
was recrystallized from alcohol (11.0 g). Overall yield
42 g (57.5%).
3-(2-Hydroxyethylsulfanyl)-1H,4H-1,2,4-triazo-
lium hydrogen oxalate (IV). Colorless transparent
prisms, triclinic crystal system; 2C4H8N3SO+·2C2HO4–
, M 235.23. Unit cell parameters: a = 8.68(1), b =
10.804(7), c = 11.44(1) Å; α = 105.09(6), β = 93.47(9),
γ = 109.21(7)°; V = 966(2) Å3; dcalc = 1.62 g/cm3; Z =
4; space group P-1 (two independent molecules); ω-
scanning, 4.39° ≤ θ ≤ 25.93°. No correction for
absorption was introduced (μMo = 3.43 cm–1). The
coordinates of hydrogen atoms on carbon atoms,
except for C5A and C5B, were calculated on the basis of
stereochemical criteria and were refined using the
riding model. Hydrogen atoms on N1A, N4A, N4B, C5A,
and C5B were localized from difference series of
electron density, and their contributions to structural
amplitudes were taken into account with fixed
3-(2-Hydroxyethylsulfanyl)-5-phenyl-1H-1,2,4-
triazole hydrochloride (V). Triazole III, 1.1 g, was
dissolved in 50 ml of methanol, concentrated
hydrochloric acid was added under stirring to the
solution until pH ~1, and the mixture was stirred for
0.5 h. The solvent was removed under reduced
pressure (water-jet pump), and the precipitate was
recrystallized first from aqueous ethanol and then from
ethanol. Yield 1.2 g (87%, calculated on the
monohydrate), colorless fine needles, mp 56–59 (PTP),
50–54°C (Boetius). IR spectrum (mineral oil), ν, cm–1:
3377, 3256, 3055, 2716, 2604, 2505, 1614, 1592,
1503, 1394, 1343, 1296, 1244, 1162, 1065, 1011, 985.
The 1H and 13C NMR spectra are given in Tables 1 and
2. Found, %: C 43.52, 43.74; H 4.93, 4.81; Cl 12.53,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

TAUTOMERISM OF AZA CYCLES: II.
477
Table 7. Coordinates of non-hydrogen atoms in the
molecule of 3-(2-hydroxyethylsulfanyl)-1H,4H-1,2,4-triazo-
5lium hydrogen oxalate (IV) in crystal and their equivalent
isotropic thermal parameters Ueq (Å2)a
Table 8. Coordinates of non-hydrogen atoms in the
molecule of 3-(2-hydroxyethylsulfanyl)-5-phenyl-1H,4H-
1,2,4-triazolium chloride monohydrate (V) in crystal and
their equivalent temperature factors B = 4/3 Σ Σ (ai,aj)B(i,j)
j=1
(Å2)
i=1
Atom
S3A
x
y
z
Ueq
Atom
x
y
z
Beq
0.2814(4)
0.5393(8)
0.158(1)
0.233(1)
0.1330(9)
0.214(1)
0.099(1)
0.467(2)
0.397(3)
0.6225(3)
0.8188(8)
0.4367(9)
0.5499(9)
0.404(1)
0.524(1)
0.352(1)
0.767(1)
0.698(1)
1.1001(8)
0.4736(2)
0.8143(6)
0.672(1)
0.6744(7)
0.4666(8)
0.5456(9)
0.550(1)
0.623(2)
0.708(2)
0.7429(2)
1.0742(6)
0.9338(8)
0.9391(7)
0.7280(8)
0.8119(9)
0.810(1)
0.892(1)
0.961(1)
0.2060(6)
–0.0160(6)
0.2497(6)
0.0287(6)
0.1078(9)
0.135(1)
0.5362(6)
0.7584(6)
0.4961(6)
0.7174(6)
0.6381(9)
0.6106(9)
0.5692(2)
0.8419(6)
0.3746(7)
0.4837(7)
0.3546(7)
0.4663(8)
0.299(1)
0.073(1)
0.076(3)
0.055(4)
0.059(3)
0.048(3)
0.049(4)
0.051(4)
0.058(7)
0.053(8)
0.065(1)
0.064(3)
0.052(3)
0.051(3)
0.048(3)
0.042(3)
0.050(4)
0.067(4)
0.076(4)
0.069(3)
0.055(3)
0.061(3)
0.060(3)
0.044(3)
0.046(3)
0.069(3)
0.063(3)
0.064(3)
0.059(3)
0.048(4)
0.044(4)
Cl1
S3
0.1348(4)
0.0634(4)
0.3059(8)
0.3414(8)
0.2244(8)
0.1626(9)
0.1766(9)
0.138(1)
0.235(1)
0.304(1)
0.291(1)
0.357(1)
0.432(1)
0.444(1)
0.380(1)
0.038(1)
0.205(1)
–0.3368(3)
–0.1282(3)
–0.0831(7)
0.4082(6)
0.1537(7)
0.1148(7)
–0.0555(7)
–0.0110(8)
0.0516(9)
0.0594(9)
–0.0516(9)
–0.051(1)
0.067(1)
0.5273(2)
0.7140(2)
0.8751(4)
0.5850(4)
0.5857(4)
0.6578(4)
0.5725(4)
0.6477(5)
0.5351(5)
0.4558(4)
0.4078(4)
0.3332(5)
0.3080(5)
0.3545(5)
0.4287(5)
0.7979(5)
0.8429(5)
6.04(7)
4.28(6)
5.8(2)
5.8(2)
3.1(2)
3.7(2)
3.2(2)
2.3(2)
2.5(2)
2.7(2)
3.3(2)
4.6(3)
5.2(3)
4.3(3)
3.5(2)
4.3(3)
5.4(3)
O8A
N1A
N2A
N4A
C3A
C5A
C6A
С7A
S3B
O8B
N1B
N2B
N4B
C3B
C5B
C6B
C7B
O9A
O8
O15
N1
N2
N4
C3
0.665(2)
0.768(2)
C5
C9
0.3238(2)
0.6203(5)
0.1552(6)
0.2475(6)
0.1412(7)
0.2367(8)
0.0926(9)
0.4325(8)
0.5307(9)
0.3176(5)
0.2142(5)
0.1318(5)
0.0442(5)
0.2307(8)
0.1321(7)
–0.1079(6)
–0.0026(5)
0.0567(5)
0.1444(5)
–0.0243(8)
0.0651(8)
C14
C13
C12
C11
C10
C6
0.176(1)
0.1727(9)
–0.0224(9)
0.022(1)
C7
O10A 1.0052(8)
O11A 0.9335(8)
O12A 0.8184(8)
C8A
C9A
O9B
O10B
O11B
O12B
C8B
R = 0.046 and Rw = 0.112 [from 1045 reflections with
F2 ≥ 4σ(I2). The coordinates of atoms are given in
Table 7. The complete set of crystallographic data was
deposited to the Cambridge Crystallographic Data
Center (entry no. CCDC 255381).
1.018(1)
0.919(1)
0.6403(8)
0.7357(8)
0.8420(8)
0.9569(8)
0.732(1)
0.846(1)
3-(2-Hydroxyethylsulfanyl)-5-phenyl-1H,4H-
1,2,4-triazolium chloride monohydrate (V).
Colorless transparent prisms, monoclinic crystal
system; C10H12N3SO+·Cl–·H2O; M 275.76. Unit cell
parameters: a = 7.629(1), b = 10.070(2), c = 16.826(5)
Å; β = 93.86(2)°; V = 1289.6(5) Å3; dcalc = 1.42 g/cm3;
Z = 4; space group P21/c; ω/2θ-scanning, θ ≤ 57.2°. No
correction for absorption was introduced (μCu = 41.22
cm–1). Hydrogen atoms were localized from difference
series of electron density, and their contributions to
structural amplitudes were taken into account with
fixed positional and thermal parameters in the final
refinement step. Total of 3400 reflections were
measured, 1322 of which were with I ≥ 3σ. The final
divergence factors were R = 0.060, Rw = 0.059 [from
968 reflections with F2 ≥ 3σ (I2)]. The coordinates of
atoms are given in Table 8. The complete set of
crystallographic data was deposited to the Cambridge
C9B
a
The equivalent isotropic thermal parameters Ueq were calculated
as one third of the trace of the orthogonalized tensor Uij.
positional and thermal parameters in the final
refinement step. The ethyl fragment in cation IVA was
found to be disordered by two positions with
populations of 0.42 and 0.58. Total of 1107
independent reflections were measured, 1045 of which
were with I ≥ 2σ. The final divergence factors were
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478
BUZYKIN et al.
rean, R., Stud. Univ. Babes-Bolyai, Chem., 2002, vol. 47,
nos. 1–2, p. 179; Ref. Zh., Khim., 2004, no. 9V85.
18. Song, C.E., Kim, J.-S., Choi, J.H., and Jin, B.W.,
Heterocycles, 1991, vol. 51, no. 1, p. 161.
Crystallographic Data Center (entry no. CCDC
273419).
ACKNOWLEDGMENTS
19. Polya, J.B., Comprehensive Heterocyclic Chemistry I,
Katritzky, A.R. and Rees, Ch.W., Eds., Oxford:
Pergamon, 1984, vol. 5, part 4A, p. 733.
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Katritzky, A.R., Rees, Ch.W., and Scriven, E.F.V., Eds.,
Oxford: Pergamon, 1996, vol. 4, p. 127.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 05-03-33008) and by the Foundation for Support
of the Russian Science.
21. Buzykin, B.I., Nabiullin, V.N., Mironova, E.V.,
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