Synthesis of 3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines

Article abstract of DOI:10.1134/S1070363211030236

A method for the synthesis of the previously inaccessible 3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepines was developed. The X-Ray diffraction data for 8-tert-butyl-3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-1, 3,4-thiadiazepine are presented.

Full text of DOI:10.1134/S1070363211030236

ISSN 1070-3632, Russian Journal of General Chemistry, 2011, Vol. 81, No. 3, pp. 573–575. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © M.V. Karpov, A.V. Khramchikhin, M.D. Stadnichuk, 2011, published in Zhurnal Obshchei Khimii, 2011, Vol. 81, No. 3, pp. 478–
480.
Synthesis of 3-Pyridin-4-yl-1,2,4-triazolo[3,4-b]-1,3,4-
thiadiazepines
M. V. Karpov, A. V. Khramchikhin, and M. D. Stadnichuk
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia
е-mail: e-mail:borisionin@mail.ru
Received June 3, 2010
Abstract—A method for the synthesis of the previously inaccessible 3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-1,3,4-
thiadiazepines was developed. The X-Ray diffraction data for 8-tert-butyl-3-pyridin-4-yl-1,2,4-triazolo[3,4-b]-
1,3,4-thiadiazepine are presented.
DOI: 10.1134/S1070363211030236
One of the methods of synthesis of 1,2,4-triazolo
[3,4-b]-1,3,4-thiadiazepines is the condensation of 4-
amino-4H-1,2,4-triazole-3-thiols with 3-substituted 2-
propynals [1]. A disadvantage of this method is the
formation of colored resinous substances as the
reaction byproducts, which reduce the yield of the
target compounds. Also, Heidel and Reid pointed out
that this technique was not suitable for the synthesis of
3-pyridin-4-yl-8-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thia-
diazepine IIIa. An attempt to condense the 4-amino-5-
pyridin-4-yl-4H-1,2,4-triazole-3-thiol II with 3-phenyl-
2-propynal led to the formation of a black viscous
multicomponent mixture.
Previously, we have reported that 1,2,4-triazolo[3,4-b]-
1,3,4-thiadiazepines may also be obtained via the con-
densation of 4-amino-4H-1,2,4-triazole-3-thiols with
N-tert-butylimine of 3-phenyl-2-propynal Ia [2]. Using
this method, we succeeded in obtaining the previously
inaccessible pyridine-containing thiadiazepines IIIa, IIIb.
H1
H2
R
NH2
N
N
MeOH
N
S
H3
t-Bu
N
R
HS
+
− t-BuNH2
N
H4
N N
N
N
N
Ia, Ib
II
R = Ph (a), t-Bu (b).
IIIa, IIIb
The structure of thiadiazepine IIIb was confirmed
by the H NMR spectroscopy and X-ray diffraction
torsion angle N4C5C10C11 describing the rotation angle
of the pyridine ring with respect to the five-membered
ring, is 31.9 deg.
1
data (see the figure and the table). The bond lengths
and bond angles of 8-tert-butyl-3-pyridin-4-yl-1,2,4-
triazolo[3,4-b]-1,3,4-thiadiazepine IIIb are listed in the
table; within experimental error they coincide with the
statistical average values [3]. The conformation of 7-
membered cycle is a boat with the deviations of atoms
S1 and N2, C2 by 0.86 and 0.67 Å, respectively. The
EXPERIMENTAL
Solvents and reagents of analytical grade were
1
used. The H NMR spectra were recorded on a Varian
XL-300 spectrometer operating at 300.13 MHz,
573

574
KARPOV et al.
Bonds lengths d (Å) and bond angles ω (deg) in the molecule IIIb
Bond
S1–C1
S1–C4
N1–C1
N1–C5
N1–N2
N2–C2
N3–C1
N3–N4
N4–C5
N5–C13
N5–C12
C2–C3
d, Å
1.7376(18)
1.7903(19)
1.375(2)
1.377(2)
1.398(2)
1.283(2)
1.309(2)
1.386(2)
1.321(2)
1.332(3)
1.337(3)
1.464(3)
Bond
d, Å
Angle
C1S1C4
C1N1C5
C1N1N2
C5N1N2
C2N2N1
C1N3N4
C5N4N3
C13N5C12
N3C1N1
N3C1S1
N1C1S1
N2C2C3
C4C3C2
C3C4C6
C3C4S1
C6C4S1
ω, deg
96.92(8)
Angle
N4C5N1
N4C5C10
N1C5C10
C4C6C8
ω, deg
C3–C4
C4–C6
C5–C10
C6–C8
C6–C7
C6–C9
C10–C14
C10–C11
C11–C12
C13–C14
C13–H13
1.339(3)
1.523(3)
1.457(3)
1.527(3)
1.529(3)
1.537(3)
1.397(2)
1.402(3)
1.379(3)
1.391(3)
0.93(2)
109.21(16)
124.37(16)
126.35(15)
111.50(19)
109.06(17)
109.1(2)
104.91(14)
129.76(15)
124.03(15)
116.62(15)
107.07(15)
108.18(15)
116.20(17)
110.58(16)
126.28(14)
122.86(13)
131.72(17)
127.01(16)
125.62(17)
118.80(14)
115.52(14)
C4C6C7
C8C6C7
C4C6C9
108.95(18)
109.1(2)
C8C6C9
C7C6C9
109.1(2)
C14C10C11
C14C10C5
C11C10C5
C12C11C10
N5C12C11
N5C13C14
C13C14C10
117.75(18)
123.70(17)
118.42(15)
118.92(17)
124.24(18)
124.94(18)
117.92(18)
solvent DMSO-d6, chemical shifts were measured
relative to internal DMSO-d6.
tion. The final values of the reliability factors are as
follows: R1 0.0364 [calculated by Fhkl for 3300
reflections with I > 2σ(I)], wR2 0.0837 (calculated by
Fhkl for all 3634 independent reflections), GOOF
1.067. All calcula-tions were performed within
SHELXTL PLUS 5 prog-rams (SHELXTL v. 5.10,
Structure Determination Soft-ware Suite, Bruker AXS,
The X-ray diffraction analysis was performed on an
automatic diffractometer SMART 1000 CCD (MoKα-
radiation, ω-scanning, θ ≤ 30°, graphite monochro-
mator). The crystals of IIIb (C14H15N5S) are rhombic,
at 120 K: a 22.2612(11), b 6.7378(3), c 9.2686(5) Å, V
1390.21 (12) Å3; space group Ρca21, Ζ 4, dcalc 1.363 g cm–3.
After averaging the equivalent reflections 3634 in-
dependent reflections (Rint 0.0191) were obtained,
which were used for solving and refining the structure.
The structure was solved by the direct methods. All
atoms were located in the difference electron density
syntheses and refined anisotropically by F2hkl. The
hydrogen atoms were refined in isotropic approxima-
Madison,
Wisconsin,
USA,
1998).
Atomic
coordinates, temperature factors, and full details of the
geometric parameters are deposited in the Cambridge
Structural Database (CCDC 725.041).
3-Pyridin-4-yl-8-phenyl-1,2,4-triazolo[3,4,-b]-
1,3,4-thiadiazepine (IIIa). To a solution of 0.012 mol
of aldimine Ia in 20 ml of methanol was added
0.01 mol of 4-amino-4H-1,2,4-triazole-3-thiol II in
small portions over several minutes under stirring
while a weak warm-up and a little darkening of the
reaction mixture was observed. The reaction progress
was monitored by TLC on Merck plates in the system
ethyl acetate-petroleum ether (1:1 by volume). The
reaction mixture was kept overnight at room tem-
perature. Then the solvent was removed under a re-
duced pressure, and the residue was recrystallized from
1
aqueous ethanol. Yield 58%, mp 225°C. Н NMR
spectrum, δ, ppm: 6.89 d (1H, H1, 3JHН 3.63 Hz), 7.46–
7.53 m (3H, Ph), 7.84–7.91 m (2H, Ph), 7.96 d (2H,
3
3
H3, JHН 5.82 Hz), 8.28 d (1H, H2, JHН 3.63 Hz), 8.70
d (2H, H4, JHН 5.82 Hz). Found, %: С 62.61; Н 4.01;
3
N 22.82. C16H11N5S. Calculated, %: С 62.93; Н 3.63;
N 22.93.
General view of the molecule of 8-tert-butyl-3-pyridin-4-
yl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazepine IIIb.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 3 2011

575
SYNTHESIS OF 3-PYRIDIN-4-YL-1,2,4-TRIAZOLO[3,4-B]-1,3,4-THIADIAZEPINES
8-tert-Butyl-3-pyridin-4-yl-1,2,4-triazolo[3,4-b]- REFERENCES
1,3,4-thiadiazepine (IIIb) was obtained similarly.
1. Heidel, N.D. and Reid, J.R., J. Heterocyclic Chem.,
1980, no. 17, p. 1087.
2. Karpov, M.V., Khramchikhin, A.V., and Stadnichuk, M.D.,
1
Yield 62%, mp 190°C. Н NMR spectrum, δ, ppm:
1.30 s (9H, t-Bu), 6.34 d (1H, H1, 3JHН 3.63 Hz), 7.95 d
3
3
(2H, H3, JHН 5.82 Hz), 8.18 (1H, H2, JHН 3.63 Hz),
Zh. Obshch. Khim., 2005, vol. 75, no. 3, p. 523.
8.66 d (2H, H4, JHН 5.82 Hz). Found, %: С 58.41; Н
3
3. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L.,
Orpen, A.G., and Taylor, R., J. Chem. Soc. Perkin
Trans. 2, 1987, no. 12, p. 1.
5.08; N 24.74. C14H15N5S. Calculated, %: С 58.82; Н
5.30; N 24.54.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 81 No. 3 2011