Reductive transformation of 3-methoxy-2-methyl-3,4-diphenyl-2,3-dihydro-1,2,5-thiadiazole 1,1-dioxide in the reaction with thiourea and HC1

Full text of DOI:10.1007/s11172-020-2776-9

Russian Chemical Bulletin, International Edition, Vol. 69, No. 2, pp. 401—404, February, 2020
401
Letters to the Editor
Reductive transformation of
3-methoxy-2-methyl-3,4-diphenyl-2,3-dihydro-1,2,5-thiadiazole 1,1-dioxide
in the reaction with thiourea and HCl
V. V. Baranov,a M. M. Antonova,a E. K. Melnikova,b,c and A. N. Kravchenkoa,d
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
E-mail: ase1313@mail.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation
cDepartment of Chemistry, M. V. Lomonosov Moscow State University,
Build. 3, 1 Leninskie Gory, 119991 Moscow, Russian Federation
dPlekhanov Russian University of Economics,
36 Stremyannyi per., 117997 Moscow, Russian Federation
1,2,5-Thiadiazole 1,1-dioxides have attracted the
attention of chemists due to pharmacological1—3 and
supramolecular4—6 properties. Hence, their synthesis and
investigation of their new chemical transformations are
of importance. Previously, our research team synthesized
a number of 1,2,5-thiadiazole 1,1-dioxide derivatives
by the reaction of 4,5-dihydroxyimidazolidin-2-ones
(thiones) with different sulfamides.7—11
To extend the scope of this unusual reductive trans-
formation of heterocycles under the action of thiourea,
we performed the reaction of the latter with 1,2,5-thia-
diazole 1,1-dioxide 1, which was synthesized by the re-
action of 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide (4)
with MеONa and MeI in MeOH at room temperature
(Scheme 1). Thiourea was found to reduce compound 1
to 2-methyl-3,4-diphenyl-2,3-dihydro-1,2,5-thiadiazole
1,1-dioxide (5) through the tautomerization of unstable
2-methyl-3,4-diphenyl-2,5-dihydro-1,2,5-thiadiazole
1,1-dioxide (6). This conclusion was made from the NMR
spectrum of compound 5, which shows the most informative
signals of protons of the C(3)H group (s, 6.41 ppm). We re-
vealed the similar enamine-imine tautomerism for N-(1,3-
dialkyl-2-thioxoimidazolidin-4-ylidene)sulfamides.13
Earlier, compound 5 was synthesized by another
method but it was characterized only by elemental analy-
In this study, we synthesized a new compound of this
class, 3-methoxy-2-methyl-3,4-diphenyl-2,3-dihydro-
1,2,5-thiadiazole 1,1-dioxide (1), and examined its ability
to undergo a reductive transformation when treated with
thiourea.
Earlier, we discovered reducing properties of thiourea12
in the unexpected transformation of 1-substituted 5-hydr-
oxy-4,5-diphenyl-1H-imidazol-2(5H)-ones (2) into 1-sub-
stituted 4,5-diphenyl-1H-imidazol-2(3H)-ones (3).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 0401—0404, February, 2020.
1066-5285/20/6902-0401 © 2020 Springer Science+Business Media LLC

Baranov et al.
402
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 2, February, 2020
Scheme 1
To sum up, we reported the first example of a reduc-
tive transformation of 3,4-diphenyl-2,3-dihydro-1,2,5-
thiadiazole 1,1-dioxides in the reaction with thiourea and
HCl. Thus, 3-methoxy-2-methyl-3,4-diphenyl-2,3-di-
hydro-1,2,5-thiadiazole 1,1-dioxide (1) is transformed
into 2-methyl-3,4-diphenyl-2,3-dihydro-1,2,5-thiadiazole
1,1-dioxide (5). The structures of compounds 1 and 5 were
established by X-ray diffraction study, which revealed
a new conglomerate.
All commercially available reagents were used as received.
The 1H and 13C NMR spectra were recorded at a temperature
from 26 to 30 C on a Bruker AM 300 spectrometer with SiMe4
as the internal standard. The ESI high-resolution mass spectra
(ESI HRMS) were obtained on a Bruker micrOTOF II spectro-
meter. The melting points were measured on a Gallenkamp
melting point apparatus (Sanyo). 3,4-Diphenyl-1,2,5-thiadiazole
1,1-dioxide (4) was synthesized from sulfamide and benzil by
a procedure described in the literature.14
Reagents and conditions: i. 1) MeONa, MeOH, 2) MeI, ~20 C,
12 h; ii. MeCN, reflux, 10 min.
3-Methoxy-2-methyl-3,4-diphenyl-2,3-dihydro-1,2,5-thia-
diazole 1,1-dioxide (1). Sodium metal (1.44 g, 0.063 mol) was
added in small pieces to MeOH (50 mL). After Na completely
reacted, 3,4-diphenyl-1,2,5-thiadiazole 1,1-dioxide (4) (9.98 g,
0.037 mol) and MeI (3.43 mL, 0.055 mol) were sequentially
added to the reaction mixture. The resulting solution was kept
for 16 h at room temperature. The crystals of the product that
formed were filtered off and dried in air. Colorless crystals were
obtained in 97% yield, m.p. 110—111 C (MeOH). 1H NMR
(DMSO-d6), δ: 2.47 (s, 3 H, NMe); 3.26 (s, 3 H, OMe);
7.36—7.52 (m, 7 H, Ph); 7.65 (t, 1 H, Ph, J = 7.4 Hz); 8.02 (d,
2 H, Ph, J = 7.7 Hz). 13C NMR (DMSO-d6): 24.13 (NMe),
51.50 (OMe), 98.62 (C—OMe), 125.60, 126.88, 129.35, 129.40,
129.79, 130.04, 135.08, 135.22 (Ph), 175.84 (C=N). Found: m/z
339.0777 [M + Na]+. C16H16N2O3S. Calculated: M + Na =
= 339.0774.
sis and the melting point.1.4 The structures of compounds
1 and 5 were established by X-ray diffraction (Fig. 1).
Compound 5 crystallizes in the non-centrosymmetric
space group Cc and contains the asymmetric carbon atom
C(2) in the S configuration. This is evidence of the self-
resolution of racemate 5 into enantiomers. The crystal of 1
contains both stereoisomers. In both of them, the five-
membered heterocycle is nearly planar; the maximum
deviation from the rms plane is 0.073(1) Å for the N(1)
atom in 1 and 0.090(3) Å in 5. The deviations of the oxy-
gen atoms O(1) and O(2) from the plane in crystal 1 are
1.333(1) and 1.098(1) Å; in 5, 1.357(2) and 1.061(3) Å,
respectively. The nitrogen atom N(1) is significantly pyr-
amidalized in both compounds, as evidenced by the sum
of the C—N—C and C—N—S bond angles (350.05(10)
and 350.82(14)º for compounds 1 and 5, respectively).
2-Methyl-3,4-diphenyl-2,3-dihydro-1,2,5-thiadiazole 1,1-di-
oxide (5). A mixture of 3-methoxy-2-methyl-3,4-diphenyl-2,3-
dihydro-1,2,5-thiadiazole 1,1-dioxide (1) (0.5 g, 0.00158 mol),
С(12)
a
b
C(15)
С(14)
C(16)
С(2)
O(3)
C(11)
С(13)
С(13)
C(15)
С(10)
N(1)
S(1)
С(14)
O(2)
С(9)
С(12)
O(1)
С(9)
N(1)
S(1)
С(2)
С(8)
С(10)
C(11)
O(1)
С(1)
С(7)
O(2)
N(2)
С(3)
С(3)
С(1)
С(8)
N(2)
С(4)
С(4)
С(7)
С(6)
С(6)
С(5)
С(5)
Fig. 1. General view of compounds 1 (a) and 5 (b) with thermal displacement ellipsoids (p = 50%). Hydrogen atoms, except for that
at the asymmetric center, are not shown.

1,2,5-Thiadiasole 1,2-dioxides
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 2, February, 2020
403
Table 1. Principal crystallographic data and the structure refinement statistics for com-
pounds 1 and 5
Parameter
1
5
Molecular formula
C
16H16N2O3S
316.37
C15H14N2O2S
286.34
Molecular weight
T/K
100
120
Crystal system
Monoclinic
P21/n
Monoclinic
Сс
Space group
Z
4
4
a/Å
11.2347(12)
13.2737(14)
11.5342(12)
117.219(2)
1529.6(3)
1.374
16.1520(8)
9.5226(5)
10.7209(10)
117.219(2)
1343.64(16)
1.416
b/Å
c/Å
β/deg
V/Å3
dcalc/g cm–3
/cm–1
2.26
2.43
F(000)
2max/deg
664
600
58
58
Number of reflections
measured
11888
4062
5412
3136
unique
with I > 3(I)
Number of refined parameters
R1
3369
3060
201
182
0.0382
0.0977
1.041
0.0275
0.0705
1.048
wR2
GOOF
Residual electron density,
0.422/–0.264
0.253/–0.225
(max/min)/e Å–3
thiourea (0.36 g, 0.00475 mol), MeCN (15 mL), and HCl (1 mL,
35%) was stirred at reflux for 10 min. Then the reaction mixture
was concentrated to dryness, and H2O (10 mL) was added. The
precipitate that formed was filtered off, washed with diethyl ether
(7 mL), and dried in air. A white powder was obtained in 55%
yield, m.p. 175—177 C (MeCN), 158—160 C (EtOH).14
1H NMR (DMSO-d6), δ: 2.65 (s, 3 H, Me); 6.41 (s, 1 H, CH);
7.30—7.42 (m, 5 H, Ph); 7.47 (t, 2 H, Ph, J = 7.5 Hz); 7.60
(t, 1 H, Ph, J = 7.4 Hz); 7.90 (d, 2 H, Ph, J = 7.8 Hz). 13C NMR
(DMSO-d6), δ: 28.69 (Me), 71.87 (CH), 128.37, 128.54, 128.88,
129.09, 129.20, 129.34, 129.49, 134.28 (Ph), 177.64 (C=N).
Found: m/z 287.0843 [M + H]+, 304.1106 [M + NH4]+, 309.0660
[M + Na]+, 325.0403 [M + K]+. C15H14N2O2S. Calculated:
M + H = 287.0849, M + NH4 = 304.1114, M + Na = 309.0668,
M + K = 325.0408.
X-ray diffraction study of compounds 1 and 5 was performed
on a Bruker APEX2 CCD diffractometer (Mo-Kα radiation,
0.71073 Å, graphite monochromator). The structures were solved
by direct methods and refined by the full-matrix least-squares
method based on F2hkl with anisotropic displacement parameters
for nonhydrogen atoms. The hydrogen atoms were positioned
geometrically and refined isotropically using a riding model. All
calculations were performed with the SHELXTL PLUS program
package.15 Principal crystallographic data and the structure re-
finement statistics are given in Table 1. Atomic coordinates and
complete structure data were deposited with the Cambridge
Crystallographic Data Centre (CCDC 1951557 for 1 and
1951558 for 5).
The X-ray diffraction study was financially supported
by the Ministry of Science and Higher Education of
the Russian Federation using equipment of the X-Ray
Structural Centre of the A. N. Nesmeyanov Institute of
Organoelement Compounds of the Russian Academy of
Sciences.
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Received September 19, 2019;
in revised form November 13, 2019;
accepted November 19, 2019