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K. Gajda et al. / Journal of Molecular Structure 1083 (2015) 137–143
poured into water. The separated solid was filtered and dried. The
Introduction
product (m.p. 196–198 °C) was recrystallized from propanol-2 and
the single crystal used for analysis was obtained from ethanol by
slow evaporation.
Fused pyrimidines along with heterocyclic compounds play an
important role in designing new classes of structural entities of
medical importance with potentially new mechanisms of action
and their great practical usefulness, primarily, due to a very wide
spectrum of their biological activities [1]. The organic molecules
are of great importance due to possible promising biological appli-
cations [2–8]. Purines, pteridines, quinazolines, pyridopyrimidines,
triazolopyrimidines, pyrazolopyrimidines, pyrimidoazepines, furo-
pyrimidines and pyrrolopyrimidines are the most important
pyrimidine derivatives [9–18]. Thienopyrimidines occupy a special
position among them [19,20]. Compounds containing fused pyrim-
idine ring make up a broad class of heterocycles that has attracted
attention in the past few years owing to its medical activities such
as anticancer [21], antiviral [22,23], antitumor [24], anti-inflamma-
tory and analgesic [25–28], antiallergic [29], antibacterial [30,31],
antihypertensive [32], antidepressant [33] and antidiabetic [34].
The appearance of qualitatively new properties of an annelated
molecule, enlargement of the possibility of varying pharmacophore
groups in different positions of the molecule, and the ability of the
latter to interact with a wider spectrum of receptors adopting var-
ious conformations are apparently of crucial importance. In addi-
tion, the structure of the molecule can be varied due to
annelation at different positions of individual heterocyclic frag-
ments. Along with some other pyrimidine systems containing an
annelated five-membered heteroaromatic ring, thienopyrimidines
are structural analogues of biogenic purines and can be considered
as potential nucleic acid antimetabolites.
1H NMR (200 MHz, DMSO): d 1.88 (br. s, 4 H), 2.86 (br. s, 2 H),
3.07 (br. s, 2 H), 1.53 (t, 3 H, Ph), 8.20 (m, 2 H, Ph), 9.56 (s, 1 H).
(III) The mixture of 5,6,7,8-tetrahydro(1)benzothieno(2,3-
d)pyrimidin-4(3H)-one (2.4 g, 0.0116 mol), dimethylaniline (7 ml)
in POC13 (30 ml) was refluxed for 4.5 h. Excess of POCI3 and
dimethylaniline was evaporated under reduced pressure. The resi-
due was poured on ice cautiously and neutralized with sodium car-
bonate solution. A precipitate formed was filtered, washed with
water and crystallized from ethanol (96%), m.p. 99–l00 °C). Then
the solution of 4-chloro-5,6,7,8-tetrahydro(1)benzothieno(2,3-
d)pyrimidine (2 g, 0.0089 mol) obtained and hydrazine hydrate
(98%, 1.33 ml) in ethanol (20 ml) was heated under reflux for 2 h.
The crystalline product formed after cooling was filtered and dried.
The product (m.p. 184–186 °C) was recrystallized from ethanol and
the single crystal used for analysis was obtained from acetonitrile
by slow evaporation.
1H NMR (200 MHz, DMSO): d 1.75 (br. s, 4 H), 2.72 (br. s, 2 H),
2.89 (br. s, 2 H), 4.55 (s, 2 H, NHNH2), 7.86 (s, 1 H, NHNH2), 8.30
(s, 1 H).
XRD data collection and refinement
The (I), (II) and (III) single-crystal X-ray diffraction experiment
were performed at 100.0(1) K on the Xcalibur diffractometer,
equipped with a CCD area detector and a graphite monochromator
The rapid growth in the literature dealing with the synthesis
and biological activity of the thienopyrimidine derivatives [35]
prompted us to undertake the synthesis of novel fused thienopyridine
derivatives with common 5,6,7,8-tetrahydro[1]benzothieno[2,3-d]
pyrimidine core, i.e. 4-hydrazino-5,6,7,8-tetrahydro[1]benzothie-
no[2,3-d]pyrimidine (I) which was a substrate for 2-phenyl-8,9,10,11-
tetrahydro[1]benzothieno[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine (II)
and3-methyl-9,10,11,12-tetrahydro-2H-[1]benzothieno[20,30:4,5]
pyrimido[1,6-b][1,2,4]triazin-2-one (III). As the crystal and molec-
ular structure of (II) have been determined previously at room
temperature [36], to obtain comparable geometry parameters for
all studied structures, herein we have redone the X-ray experiment
at 100 K.
for the Mo K
device. The reciprocal space was explored by
a
radiation, with an Oxford Cryosystem N2 gas stream
-scans. The reflec-
x
tions were measured with a radiation exposure time from 4 to
20 s, according to diffraction intensities. The detector was posi-
tioned at 60 mm distance from the crystal. The diffraction data of
studied compounds was performed using the CrysAlis CCD [37].
Further details on the crystal data collection, processing and exper-
imental conditions are given in Table 1. The structure of (I), (II) and
(III) was solved by direct methods and refined by a full-matrix
least-squares method using SHELXL14 program [38]. Lorentz and
polarization corrections were applied. All hydrogen atoms were
located from difference Fourier synthesis. Non-hydrogen atoms
were refined anisotropically. In structures, H atoms refined using
a riding model. The structure drawings were prepared using SHEL-
XTL, SHELXS14 and SHELXL14 programs [30]. The packing draw-
ings were prepared using Mercury 3.1.1 [39]. Supplementary
crystallographic data can be found in the CCDC deposit CCDC
995332 for (I), CCDC 995342 and (II) and CCDC 995360 for (III).
Data can be obtained free of charge from the Cambridge Crystallo-
Experimental
Synthesis and crystallization
(I) Ethylpyruvate (4.23 ml, 0.0386 mol) and 4-hydrazino-5,6,7,8-
tetrahydro(1)benzothieno(2,3-d)pyrimidine (8.5 g, 0.0386 mol) in
acetic acid (10 ml) were heated under reflux for 4 h. The crystalline
product formed after cooling was filtered, washed with water and
dried. The product (m.p. 235–237 °C) was recrystallized from
propanol-2 and the single crystal used for analysis was obtained
from acetonitrile by slow evaporation.
Theoretical calculations
Based on the solid-state geometry, the molecular structures of
(I), (II) and (III) were optimized using the B3LYP hybrid functional
[40–42] with the 6-311++G(d,p) level of theory. All species corre-
spond to the minima at the B3LYP/6-311++G(d,p) level with no
imaginary frequencies. All calculations were performed using the
GAUSSIAN09 program package [43].
1H NMR (200 MHz, DMSO): d 1.81 (br. s, 4 H), 2.85 (br. s, 2 H),
3.03 (br. s, 2 H), 2.48 (s, 3 H, CH3), 8.92 (s, 1 H).
(II) To the solution of 4-hydrazino-5,6,7,8-tetrahydro(1)benzo-
thieno(2,3-d)pyrimidine (0.5 g, 2.27 mmol) in dry acetonitrile
(15 ml) triethylamine (0.29 ml, 2.27 mmol) and benzoyl chloride
(0.26 ml, 2.27 mmol) was added. The mixture was heated under
reflux for 1 h and evaporated under vacuum. The residue was
washed with water, dried and crystallized from acetonitrile. The
solution of N0-(5,6,7,8-tetrahydro(1)benzothieno(2,3-d)pyrimidin-
4-yl)benzohydrazide (m.p. 160–162 °C) (0.5 g, 1.54 mmol)
obtained in acetic acid (10 ml) was heated under reflux for 4 h then
Results and discussion
Synthesis
The synthesis of 1,2,4-triazolothieno[2,3-d]pyrimidine system
has been reported in a number of publications [44–46].