Solvent mediated reaction of 1-methyl-1H-tetrazoline-5-thione with iodine

Article abstract of DOI:10.1007/s11224-010-9710-y

1-Methyl-1H-tetrazoline-5-thione (1) reacts with iodine in CHCl₃ with formation of 1:1 stable σ-complex (logβ = 3.8 ± 0.1 is found by spectrophotometry). In the ethanol solution irreversible oxidation with formation of disulfide product 5,5-dithiobis(1-methyl-1H-tetrazole) (2) is observed. The structure of (2) was determined by X-ray diffraction. Strong intermolecular interactions with shortened contacts are observed between sulfur atom of disulfide bridge and heterocyclic nitrogen of the neighboring molecule (S???N 3.0179(15) A) forming infinite supramolecular chains which are further linked with π-π stacking interaction of tetrazole rings (interplane distance is 3.1685(6) A).

Full text of DOI:10.1007/s11224-010-9710-y

Struct Chem (2011) 22:313–317
DOI 10.1007/s11224-010-9710-y
ORIGINAL RESEARCH
Solvent mediated reaction of 1-methyl-1H-tetrazoline-5-thione
with iodine
•
Nataliya V. Aleshina Margarita S. Chernov’yants
•
•
Igor N. Shcherbakov Zoya A. Starikova
Received: 16 September 2010 / Accepted: 9 December 2010 / Published online: 24 December 2010
ꢀ Springer Science+Business Media, LLC 2010
Abstract 1-Methyl-1H-tetrazoline-5-thione (1) reacts
with iodine in CHCl3 with formation of 1:1 stable
r-complex (logb = 3.8 0.1 is found by spectrophotom-
etry). In the ethanol solution irreversible oxidation with
formation of disulfide product 5,50-dithiobis(1-methyl-
1H-tetrazole) (2) is observed. The structure of (2) was
determined by X-ray diffraction. Strong intermolecular
interactions with shortened contacts are observed between
sulfur atom of disulfide bridge and heterocyclic nitrogen of
the central nervous system. These compounds have
anti-inflammatory, antilipemic, antimicrobial, and antial-
lergic activities [1]. Moreover, such compounds possess
anti-thyroidal effect same N-methylimidazoline-2-thione
(methimazole) or 3-methyl-2-thioxo-4-imidazoline-1-ethyl-
carboxylate (carbimazole) [2].
Studies on the formation of heterocyclic thiones
n–r* complexes such as N-methylbenzothiazole-2-thione,
N-methylimidazoline-2-thione, 2-imidazolidinethione with
molecular iodine were motivated by an interestin elucidation
of the mechanism of action of antithyroid drugs used for the
treatment of hyperthyreosis [3]. It is known [4] that the
reaction of 2-imidazolidinethione with an aqueous solution
of I2 in KI is accompanied by oxidation of thione to give the
dimeric product, viz., 2,20-dithiobis(imidazolidine). The
reaction of methimazole with molecular iodine in CH2Cl2 in
a molar ratio of 1:2 gave the [(C4H6N2S-)2]I8 compound
containing the 2,20-dithiobis(1-methylimidazolium) dica-
˚
the neighboring molecule (SꢀꢀꢀN 3.0179(15) A) forming
infinite supramolecular chains which are further linked
with p–p stacking interaction of tetrazole rings (interplane
˚
distance is 3.1685(6) A).
Keywords X-ray structure ꢀ Heterocyclic compounds ꢀ
Stability constant ꢀ Iodine chemistry
2-
Introduction
tion and the Z-shaped I8 counterion [5]. The crystal and
molecular structure of the compound with composition
[(C4H6N2)S]2(I3)2I2—the oxidation product of methimazole
with molecular iodine in CHCl3 was established by X-ray
diffraction [6]. The reaction of thiazolidine-2-thione with
molecular iodine in a molar ratio of 1:2 affords the iodonium
salt [(C3H5NS2)2I?] I3-I2 as a result of heterolytic dispro-
portionation of the iodine molecule [2]. The crystal structure
of the reaction product of 5-methyl-1,3,4-thiadiazoline-
2-thion with molecular iodine in CHCl3 consists of the iod-
onium cations (C3H4N2S2)2I? and the pentaiodide anions
Tetrazole compounds have a wide range of pharmaceutical
applications, where they act as stimulants or sedatives on
N. V. Aleshina
Southern Scientific Center of Russian Academy of Sciences
(SSC RAS), 41, Chehova Str., Rostov-on-Don 344006,
Russian Federation
M. S. Chernov’yants ꢀ I. N. Shcherbakov (&)
Southern Federal University, 7, Zorge Str.,
Rostov-on-Don 344090, Russian Federation
e-mail: shcherbakov@sfedu.ru
-
I5 [7]. Organic disulfide—5,50-dithiobis(1-phenyl-1H-
tetrazole), C14H10N8S2, have been isolated during an attempt
to prepare an unsymmetrical disulfide [8].
Z. A. Starikova
It was shown [9, 10] that the mechanism of reaction (the
formation of disulfide or iodonium salt) depends on the
electron-releasing properties of the thione molecule
A. N. Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences, Moscow 119991,
Russian Federation
123

314
Struct Chem (2011) 22:313–317
determined by the nature of heteroaromatic moiety and the
character of the oxidizing agent and the solvent used. The
adiabatic ionization potentials of heteroaromatic thiones
are rather low due to which they are readily oxidized to
form radical cations or thiyl radicals as a result of the loss
of the hydrogen atom from thione [11]. Ability of hetero-
aromatic thioamides to interact with iodine, stoichiometry
and stability of charge transfer complexes, molecular and
crystal structures have been studied by several authors
[12–19].
The stability constant was calculated by the least squares
method according to Eq. 2, the linearized form of Eq. 1:
ꢀ
ꢁ
Ai
Ai
log
¼ log b þ n log cI ꢂ n
cL
ð2Þ
2
Amax ꢂ Ai
Amax
where Amax is the absorbency of a solution, in which thione
is almost completely involved in the adduct
L
(kmax = 308 nm); Ai is the absorbency of solutions con-
taining thione L and the molecular adduct; b is the stability
constant, n is the number of iodine molecules coordinated
by thione L; cI , cL are the total concentrations of molec-
ular iodine and thione, respectively.
The aim of the present study was to study the reaction of
1-methyl-1H-tetrazoline-5-thione (1) with elemental iodine
in chloroform and ethanol solutions.
2
The calculated from experimental data least squares line
(2) is y = 0.972x ? 3.83 (q = 0.992). From which it can
be concluded that L coordinates only one iodine molecule
and estimated logb = 3.8 0.1.
Results and discussion
Mixing of the same reagents in ethanol solution resulted
in rapid irreversible oxidation of the thione with formation
of disulfide 5,50-dithiobis(1-methyl-1H-tetrazole), which
molecular and crystal structure was studied by X-ray dif-
fraction data.
In chloroform solution reversible complex formation was
observed and studied by UV/vis spectroscopy.
L + nI2 ꢀ L ꢀ nI2
The molecular structure of 5,50-dithiobis(1-methyl-1H-
tetrazole) with the atom-numbering scheme is shown in
Fig. 2 and selected geometric parameters are given in
Table 1.
The number of I2 molecules coordinated by thione (L) in
solution and the stability constant of the molecular adduct
of (I) with iodine were estimated by spectrophotometry
based of the shift of the reaction equilibrium:
The conformation of the molecule in crystal is not
symmetrical, two formally identical thiotetrazole moieties
interconnected with disulfide bridge are rotated relative to
each other around S–S line (the C1–S1–S2–C2 torsion
angle is 80.83(8)ꢁ). Both tetrazole rings are strictly planar
due to p-conjugation (larges deviation of atoms from the
½L ꢀ nI2ꢁ
b ¼
ð1Þ
n
½Lꢁ½I2ꢁ
The UV/visible absorption spectra of solutions
containing thione at a constant concentration and iodine
at concentrations varied from 4 9 10-5 up to 1.2 9 10-3
mol/L are presented in Fig. 1.
˚
least squares planes is 0.006(2) A).
The bond lengths and angles are rather close in the two
thiotetrazole moieties of the molecule, the most deviating are
˚
two N–N bond pairs: N1–N2, 1.341(2) A and N6–N7,
˚
1.352(2) A) and (N3–N4, 1.356(2) A and N8–N9,
˚
˚
1.367(2) A). S–C bond lengths are nearly the same (S1–C1,
˚
˚
1.7512(18) A and S2–C3, 1.7532(18) A) though orientation
of tetrazole rings p-systems relative to S–S bond are differ-
ent. The angle between ls plane of ‘‘first’’ tetrazole ring (with
C1 atom) and S1–S2 bond is 59.67(7)ꢁ, whilst the same one
for the second ring (with C3 atom) is 15.86(7)ꢁ (Table 1).
˚
The S1–S2 bond length (2.0484(6) A) is rather short for
acyclic disulfide bridge connecting five-membered hetero-
˚
cycles (common range is 2.013–2.141 A) which is typical
˚
for bis-thiotetrazole derivatives (compare with 2.0128(9) A
0
˚
in 5,5 -dithiobis(1-phenyl-1H-tetrazole [8] and 2.026(2) A
in bis(1-(2,6-dimethylphenyl)-1,2,3,4-tetrazol-5-yl)disulfane
[20].
Hydrogen atoms on both methyl groups are disordered
over two sets of positions with equal occupancy corre-
sponding to internal rotation of methyl groups around N–C
bond.
Fig. 1 Electronic absorption spectra of solutions of thione
(4.0 9 10-5 mol/L) and molecular iodine at the concentrations:
4.0 9 10-5 (1), 8.0 9 10-5 (2), 1.6 9 10-4 (3), 3.2 9 10-4 (4),
4.8 9 10-4 (5), 8.0 9 10-4 (6), and 1.2 9 10-3 mol/L (7)
123

Struct Chem (2011) 22:313–317
315
Fig. 2 Structure of the
compound C4H6N8S2 (2)
(thermal ellipsoids are drawn at
50% probability)
disulfide sulfur atom. C1 and N3i contact is also extremely
˚
Table 1 Selected geometric parameters (A, ꢁ)
˚
˚
short—2.932(2) A (0.32 A less than vdW radii sum). Also
not common is the arrangement of the interacting moieties of
the molecules which are placed in the crystal in such a way
that S–SꢀꢀꢀNi angle is 166.82(6)ꢁ and S1 goes out of the mean
Parameter
Value
˚
Bond lengths (A)
S1–C1
N1–C1
1.7520(16)
1.3415(19)
1.3414(18)
1.3031(19)
1.3564(19)
1.323(2)
i
˚
plane of tetrazole moiety of N3 only by 0.305 A, S–S bond is
N1–N2
nearly parallel to this plane.
N3–N2
Nitrogen atom N3 of the same thiotetrazole moiety is
involved into similar with earlier described interaction with
S1ii and C1ii atoms of another molecule (symmetry code:
(ii) 1 - x, 1/2 ? y, 1/2 - z). Connected in such ‘‘head-to-
tail’’ manner molecules of disulfide form infinite one-
dimensional zigzag chains which propagate along (b) axis
of the crystal as shown in Fig. 3. These chains are formed
due to interactions in which only one of the two tetrazole
moieties present in the molecule is involved (with S1 and
C1 atoms in it).
N4–N3
N4–C1
N1–C2
1.456(2)
S1–S2
2.0482(6)
1.7530(16)
1.336(2)
S2–C3
N6–C3
N6–N7
1.3528(19)
1.293(2)
N8–N7
N9–N8
1.3704(19)
1.326(2)
Infinite one-dimensional supramolecular chains are
‘‘zipped’’ with one another into two-dimensional layer
(which is paralleled to (01-1) plane) by interaction in which
the ‘‘second’’ thiotetrazole moiety of the molecules is
taking part (with S2 and C3 atoms within it). Connection
between infinite chains is accomplished by p–p stacking
interactions of tetrazole rings (Fig. 3).
N5–C3
N6–C4
1.459(2)
Bond angles (ꢁ)
C1–S1–S2
C3–S2–S1
Torsion angles (ꢁ)
C1–S1–S2–C3
101.60(5)
102.02(6)
80.83(8)
Least squares planes of interacting rings are strictly
˚
parallel to each other and are separated by 3.1687(7) A
Crystal packing of the molecules appears to be very
interesting and worth discussing. Intensive intermolecular
interaction between S1 and N3i atoms is observed with very
(distance between tetrazole ring’s centroids is
˚
3.2256(10) A). Rings slip relative to each other in such a
way that C3 and N8 atoms are almost directly above N8iii
and C3iii atoms of another molecule, correspondingly
˚
short interatomic distance of 3.0179(17) A between atoms
˚
(symmetry code: (i) 1 - x, -1/2 ? y, 1/2 - z). It is 0.33 A
(symmetry code: (iii) 1 - x, 2 - y, -z). Interatomic dis-
tances in C3ꢀꢀꢀN8iii and C3 ꢀꢀꢀN8 contacts are 3.179(2) A
iii
˚
shorter than sum of the van der Waals radii and is the shortest
intermolecular contact registered in Cambridge Structural
Database up to date (CSD [21], version 5.31 ? updates
November 2009) between heterocyclic nitrogen and acyclic
˚
long and by 0.07 A shorter than sum of interacting atom’s
vdW radii. In CSD there is no example of such arrange-
ment of tetrazole rings in the crystal state and the rings
123

316
Struct Chem (2011) 22:313–317
MS spectra of 2 were recorded in positive and negative
electrospray mode with a Thermo Finnigan Surveoyor
MSQ spectrometer (energy of ionization about 1–3 eV).
ESI(?)-MS m/z (Ir, %): 230.9 [M ? H]? (100); 174.9
[M ? H-2N2]? (17.9); 147.9 [M ? 2H-3N2]?• (15.5);
118.9 [M ? H-4N2]? (20.2).
ESI(-)-MS m/z (Ir,%): 115.1 [M/2]-• (100).
The electronic absorption spectra of chloroform solu-
tions containing thione (1) and molecular iodine in differ-
ent ratios were registered on a Cary 100 UV–visible
spectrophotometer in quartz cells with a 1.0 cm in the
250–800 nm region. Chloroform solutions of thione
(2.0 9 10-3 mol/L) and iodine (2.0 9 10-3 mol/L) were
used as starting solutions. Equilibrium constant measure-
ments were performed at 22 0.5 ꢁC.
The crystals were obtained by mixing ethanol solutions
of thione (1) and molecular iodine in a molar ratio of 2:3
followed by slow evaporation of the solvent in air. The
resulting light brown oil was recrystallized from ethanol
with replacement of solvent to obtain needle-like beige
crystals.
Fig. 3 Supramolecular interactions in the crystal structure of
C4H6N8S2 (hydrogen atoms are omitted for clarity). Symmetry codes:
(i) 1 - x, -1/2 ? y, 1/2 - z; (ii) 1 - x, 1/2 ? y, 1/2 - z; (iii) 1 - x,
2 - y, -z
Crystal data are shown in Table 2. The crystal structure
was solved by direct methods followed by calculations of
Fourier maps with the use of the SHELXS-97 [23] program
package. C-bound H atoms were positioned geometrically
interplane separation is one of the shortest found for
interacting five-membered heteroaromatic systems.
The infinite quasi two-dimensional layers are linked by
two infinite chains of CHꢀꢀꢀN interactions of tetrazole ring
nitrogen atoms and H atom of the methyl group of another
molecule, both propagating along (a) crystal axis. First
chain is formed by N4ꢀꢀꢀH2Eiv and H2EꢀꢀꢀN4v interac-
˚
(C–H 0.96 A) and were refined as riding on their parent
atoms, with Uiso(H) = 1.5 Ueq(parent atom). The experi-
mental data had been corrected for absorption effects with
a sadabs procedure [24] with Tmin/Tmax = 0.847/0.893.
PLATON [25] and Mercury v. 2.3 software [26] were used
to prepare material for publication.
˚
˚
tions which are 2.47 A long (0.28 A less than vdW sum),
second—by contacts N8ꢀꢀꢀH4Av and H4AꢀꢀꢀN4iv—which
˚
˚
are 2.54 A long (0.21 A less than vdW sum; symmetry
codes: (iv) 1 - x, y, z; (v) 1 ? x, y, z).
CCDC-783408 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
To summarize, we showed that the weakly polar
aprotic solvent (CHCl3) favors formation of the stable
molecular complex of thione (1) with iodine. The dipolar
amphiprotic solvent (C2H5OH) forms the n–r* complex
with iodine molecule characterized by a substantial
charge transfer and initiates the formation of oxidation
disulfide product (2). These facts were confirmed by the
UV/vis-spectrophotometric and X-ray diffraction data. In
the crystal state unusual intermolecular interactions are
observed.
Table 2 Crystal data
3
˚
V = 898.97(13) A
C4H6N8S2
Mr = 230.29
Monoclinic, P21/c
Z = 4
Mo Ka
a = 6.2740(5) A
˚
b = 8.0175(7) A
l = 0.57 mm-1
T = 100(2) K
0.45 9 0.20 9 0.15 mm
˚
˚
c = 18.1878(14) A
Bruker APEX II CCD area detector’
diffractometer
2386 independent
reflections
Absorption correction: multi-scan
SADABS (Bruker, 2005)
1952 reflections with
I [ 2r(I)
Rint = 0.043
Experimental
Tmin = 0.873, Tmax = 0.919
10415 measured reflections
R[F2 [ 2r(F2)] = 0.030
wR(F2) = 0.073
1-Methyltetrazoline-5-thione (1) (98%, Aldrich) was used
without additional purification. 5,50-Dithiobis(1-methyl-
1H-tetrazole) (2) was synthesized by mixing ethanol
solutions (15 mL) of compound (1) (1 mmol, 0.1162 g)
and iodine (2 mmol, 0.5076 g). The solvents were purified
according to known procedures [22].
129 parameters
H atom parameters
constrained
-3
˚
S = 1.01
Dqmax = 0.33 e A
-3
˚
2386 reflections
Dqmin = -0.29 e A
123

Struct Chem (2011) 22:313–317
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