Structural characterization of new compound from the ring-opening reaction of 3-(1H-1,2,4-triazol-1-yl)-1,5-benzothiazepine with phenylonitrile oxide

Article abstract of DOI:10.1007/s10870-010-9911-7

The crystal structure of the product (Z)-2-((Z)-((Z)-1,3-diphenyl-2-(1H-1, 2,4-triazol-1-yl)allylidene)amino) phenyl N-hydroxybenzimidothioate (4) was obtained by single crystal X-ray diffraction. The title compound, C ₃₀H₂₃N₅

Full text of DOI:10.1007/s10870-010-9911-7

J Chem Crystallogr (2011) 41:514–518
DOI 10.1007/s10870-010-9911-7
ORIGINAL PAPER
Structural Characterization of New Compound from the Ring-
Opening Reaction of 3-(1H-1,2,4-triazol-1-yl)-1,5-Benzothiazepine
with Phenylonitrile Oxide
•
•
•
Sheng-Qin Chen Fei Ding Yi-Chao Zhang
Fang-Ming Liu
Received: 13 April 2010 / Accepted: 17 November 2010 / Published online: 8 December 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The crystal structure of the product (Z)-2-((Z)-
((Z)-1,3-diphenyl-2-(1H-1,2,4-triazol-1-yl)allylidene)amino)
phenyl N-hydroxybenzimidothioate (4) was obtained by
single crystal X-ray diffraction. The title compound,
C30H23N5OS (4), crystallizes in the triclinic space group,
Keywords Benzimidothioate ꢀ Allylidene ꢀ
1,2,4-triazole ꢀ Crystal structure
Introduction
˚
P-1, with unit cell parameters a = 8.3306(17) A, b =
˚
˚
11.394(2) A, c = 14.560(3) A, a = 78.75(3)8, b = 89.96(3)8,
c = 70.56(3)8, Z = 2. In the crystal structure, adjacent
molecules are linked by O–HꢀꢀꢀN hydrogen bonds. H-bonds
and p–p stacking are the main non-bonding interactions in
the molecular structure and give support to molecular
packing stability. In addition, the structure is supported by a
weak intermolecular C–HꢀꢀꢀCg p-ring interaction. Detail of
the synthesis, structures, and spectroscopic properties of the
title compound is discussed.
Owing to their remarkable chemotherapeutic applications,
1,5-benzothiazepines [1–3] have been the object of intense
investigation in medicinal chemistry and same of them are
nowadays among the most widely used drugs in the treat-
ment of cardiovascular disorders, such as Diltiazem
[4],Thiazesim [5], and Clentiazem[6], etc. On account of
this, a great deal of work has been done on the synthesis of
1,5-benzothiazepine derivatives aimed at defining its bio-
chemical and pharmacological role [7–10]. Recently,
annulated 1,5-benzothiazepine derivatives have attracted
increasing attention with consideration that the addition of
a third ring to bond [d] may be expected to enhance the
activilty or modify the activity profile [11–14]. In addition,
1,2,4-triazole derivatives represent one of the most inter-
esting and important classes of compounds, possessing a
widespread biological activities such as antimicrobial and
antifungal activities [15–19]. Many triazole derivatives, for
example, fluconazole and itraconazole, have been com-
mercially available antifungal agents [20, 21]. Meanwhile,
the introduction of 1,2,4-triazole moiety into the parent
compounds may improve the properties and biological
activities of the compounds, it is therefore thought of
interest to combine these two potential biologically active
units into a single molecule for evaluating their biological
activity.
S.-Q. Chen ꢀ F.-M. Liu (&)
College of Materials and Chemical Engineering,
Hangzhou Normal University, Hangzhou 310036,
People’s Republic of China
e-mail: fmliu859@sohu.com
F. Ding
Technology Center of Juhua Group, Quzhou 324004,
People’s Republic of China
Y.-C. Zhang
WuXi PharmaTech Co., Ltd, Shanghai 200131,
People’s Republic of China
A literature survey shows that 1,5-benzothiazepines with
a 1,2,4-triazole moiety substituted at 3-position have never
been reported so far. Taking into consideration of the
important biological activity of 1,5-benzothiazepine and
F.-M. Liu
College of Chemistry and Chemical Engineering, Xinjiang
University, Urumqi 830046, People’s Republic of China
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J Chem Crystallogr (2011) 41:514–518
515
O
SH
O
N
HN
O
HC
O
C
N
H2
C
N
NH 2
N
N
C
CH 2Br
Piperidine
N
N
Et3
N
N
1
2
S
S
N
N
solvent
N
N
N
N
N
H
N
3
3'
Cl
Cl
OH
N
OH
N
Et3N
Et3N
N
N
N
H
S
N
N
N
N
N
S
4'
4
O
N
O
H
N
Scheme 1 The synthesis of title compound
1,2,4-triazole moieties, as an extension of our investiga-
tions on the synthesis of new 1,5-benzothiazepine deriva-
tives [22, 23], it is reported here the synthesis of a new
compound of 1,5-benzothiazepine with a 1,2,4-triazole
moiety substituted at 3-position and its reaction with
phenylonitrile oxide, expecting to get the desired normal
cycloadduct (40) Scheme 1. Unfortunately, we only
obtained the ring-opening product (4). The crystal structure
of the molecular (4) was first determined by single-crystal
X-ray diffraction (Fig. 1).
obtained using R-AXIS SPIDER X-ray diffraction.The
starting compounds 1, 2 were prepared according to the
previously reported procedures [24, 25].
The Synthesis of 1,5-benzothiazepine Containing
1,2,4-triazole (3)
To a solution of chalcone (2) (4.0 mmol) in methanol
(60 ml) was added o-aminothiophenol (4.0 mmol). The
reaction mixture was kept under stirring at room temper-
ature for 0.5 h.The mixture was heated under reflux for
20–30 min and then added CF3COOH (1.2 ml). The re-
fluxing was continued for 5–6 h. About half of the solvent
was distilled off and the resulting mixture was allowed to
stand at room temperature. The crystalline solid product
thus separated by filtered, washed by cold methanol
(2–3 mL) and dried. The crude compound was recrystal-
lized from methanol.
Experimental
Reagents and Apparatus
All reagents were of commercial availability. Melting
points were measured on a mettler FP-5 capillary melting
point apparatus and were uncorrected. Elemental analyses
were performed on a Perkin-Elmer 2400 elemental ana-
lyzer. The IR spectra were determined as potassium
bromide pellet on a Bruker Equinox 55 FT-IR spectro-
photometer. The [1] H-NMR spectra were recorded on a
Varian Inova-400 spectrophotometer using TMS as an
internal standard. EI-ms spectra were recorded with an
Agilent 5975 apparatus. X-ray crystal structure was
3: White crystal, Yield 72.7%. m.p.209–211 °C. 1H-NMR
(CDCl3, 400 MHz) d: 8.00–6.70 (m, 16H), 6.10(m,0.5H),
5.88–5.85 (d, J = 12.0 Hz, 0.5H), 5.55–5.52 (d, J =
12.0 Hz, 0.5H), 5.43 (m,0.5H); IR (KBr): 3244, 3050, 1672,
1587, 1475, 699 cm-1; MS (70 eV) m/z (%): 382 (M ?),
313, 212 (100), 109, 65, 51; Anal.Calcd. for C23H18N4S: C,
72.22; H, 4.74; N, 14.65; Found C, 72.04; H, 4.817; N, 14.57.
123

516
J Chem Crystallogr (2011) 41:514–518
Fig. 1 ORTEP view and packing diagram of molecular structure of the title compound with 50% thermal ellipsoids. Dashed lines indicate
hydrogen bonds
The Synthesis of (Z)-2-((Z)-((Z)-1,3-diphenyl-
2-(1H-1,2,4-triazol-1-yl)allylidene)amino)phenyl
N-hydroxybenzimidothioate (4)
petroleum (V:V = 1:5). A yellow crystal 4 cultured from
methanol.
4: Yellow crystal, Yield 27.3%. m.p.203–205 °C.
1HNMR (CDCl3, 400 MHz) d 6.15(1H,s); 8.59(1H,s);7.97,
8.28 (2H,2 s), 6.53–7.61 (19H,m) IR (KBr): 3384, 2360,
1635,1586, 1352, 761 cm-1; MS (70 eV) m/z (%): 501
(M ?), 432, 382, 313, 212 (100), 109, 77, 51; Anal. Calcd.
for C30H23N5OS: C,71.83; H,4.62; N,13.96; Found C,
71.83; H, 4.613; N, 13.97.
Benzohydroximinoyl chloride (1.5 mmol) was added under
stirring to a solution of appropriate (E)-2,4-diphenyl-
3-(1H-1,2,4-triazol-1-yl)-2,5-dihydrobenzo[b] [1, 4] thia-
zepine 3 (1 mmol) in methylene chloride (30 ml) and a
solution of triethylamine (1.5 mmol) in the same solvent
(5 ml) was added dropwise slowly. The reaction mixture
was kept under magnetic stirring at room temperature for
4 days. After the completion of the reaction, the solvent
was evaporated off at reduced pressure, and ether was
added and the triethylamine hydrochloride was filtered.
After removal of the solvent, the residue was purified by
silica gel column chromatography with ethyl acetate/light
X-ray Crystallography
The X-ray diffraction data of the single crystal 4 was col-
lected on a crystal of approximate dimensions 0.540 9
0.240 9 0.180 mm by using Rigaku R-axis Spider diffrac-
tometer with graphite-monochromated MoKa radiation. All
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J Chem Crystallogr (2011) 41:514–518
517
˚
C(11)–C(12), 1.497(3) A; C(8)–C(11), 1.478(3) A; C(24)–
˚
Table 1 Summary of structure determination of compounds 4
˚
C(25), 1.483(3) A; N(1)–C(8), 1.434(3) A; N(4)–C(18),
˚
CCDC deposition number
Formula
771603
˚
1.413(3) A and C(7)–C(8), 1.335(3) A; C(11)–N(4),
˚
C30 H23 N5 O S
501.59
˚
˚
1.285(3) A; C(24)–N(5), 1.280(3) A, indicates it is a dou-
ble bond between C(7) and C(8), C(11) and N(4) as well as
N(5) and C(24) (Table 2). Besides, the molecule adopts a
cis configuration about the central C=C and two C=N
bonds. The four atoms of S1, C24, N5, O1 and C7, C8,
C11, N4 are nearly coplanar, with its mean deviation from
Formula weight
Crystal size (mm)
Temperature (K)
Crystal colour
0.54 9 0.24 9 0.18
288(2)
Yellow
Crystal system
Space group
Triclinic
P-1
˚
plane being 0.0069 and 0.0523 A, respectively. Further-
Unit cell dimensions [A°] and angles (°)
˚
a (A)
more, the structure is characterized by the torsion angles:
C(6)–C(7)–C(8)–N(1): 2.0(4), N(1)–C(8)–C(11)–N(4):
-9.6(3), C(18)–N(4)–C(11)–C(12): -6.7(4) (Table 2).
8.3306 (17)
˚
b (A)
11.394 (2)
14.560 (3)
78.75 (3)
89.96 (3)
70.56 (3)
1275.2 (4)
2
˚
c (A)
a (°)
b (°)
c (°)
˚
Table 2 Selected bond lengths (A), bond angles (8), and torsion
angles (8) for compound 4
3
˚
Compound 4 (bond lengths (A))
˚
Volume (A )
N(1)–C(8)
1.434 (3)
1.285 (3)
1.413 (3)
1.280 (3)
1.467 (3)
1.335 (3)
1.478 (3)
1.497 (3)
1.483 (3)
1.394 (3)
1.772 (2)
1.779 (3)
Z
N(4)–C(11)
Density (calculated)
(Mg/m^3)
Absorption coefficient (mm-1
F(000)
1.306
N(4)–C(18)
N(5)–C(24)
)
0.160
C(6)–C(7)
524
C(7)–C(8)
Theta range for data collection
Index ranges
3.05-27.47°
C(8)–C(11)
-10 \=h \=10, -14 \=k \=14,
-18 \=l \=18
12128/5624
C(11)–C(12)
Reflections collected/unique
R(int)
C(24)–C(25)
0.0370
O(1)–N(5)
Refinement method
Goodness of fit ref
Full-matrix least-squares on F^2
1.022
S(1)–C(24)
S(1)–C(23)
Final R indices [I [ 2.0 r(I)]
R indices (all data)
R1 = 0.0569, wR2 = 0.1177
R1 = 0.0956, wR2 = 0.1397
0.198 and -0.271 e.A^-3
Compound 4 (bond angles (8))
N(5)–O(1)–H(1A)
C(24)–S(1)–C(23)
C(11)–N(4)–C(18)
C(24)–N(5)–O(1)
N(1)–C(8)–C(11)
N(4)–C(11)–C(8)
C(8)–C(11)–C(12)
C(19)–C(18)–N(4)
C(18)–C(23)–S(1)
N(5)–C(24)–C(25)
N(5)–C(24)–S(1)
C(25)–C(24)–S(1)
Compound 4 (torsion angles (8))
C(6)–C(7)–C(8)–N(1)
C(18)–N(4)–C(11)–C(12)
N(1)–C(8)–C(11)–N(4)
C(18)–N(4)–C(11)–C(8)
C(7)–C(8)–C(11)–N(4)
C(7)–C(8)–C(11)–C(12)
S(1)–C(24)–C(25)–C(30)
C(23)–S(1)–C(24)–C(25)
109.5
Largest diff. Pesk and hole
101.69 (11)
124.04 (19)
111.4 (2)
calculation was carried out on a computer with the aid of the
SHELX-97 [26] and PLATON [27], program and refinements
on F2 were performed by full-matrix least-squares techniques
with anisotropic displacement parameters for the non-hydro-
gen atoms. A summary of the crystallographic data and detail
of the structure refinement are listed in Table 1.
115.83 (17)
116.46 (19)
117.54 (18)
123.0 (2)
119.18 (18)
117.2 (2)
CCDC 771603 for the corresponding compound of 4
contain the supplementary crystallographic data for this
paper. This data can be obtained free of charge from
Cambridge Crystallographic Data Centre (CCDC)12 Union
Road, Cambridge CB2 1EZ, UK; phone: ? 44(0)1223-
336408; fax: ? 44(0)1223-336033; email: deposit@ccdc.
cam.ac.uk;http://www.ccdc.cam.ac.uk.
122.18 (19)
120.44 (16)
2.0 (4)
-6.7 (4)
-9.6 (3)
176.8 (2)
169.2 (2)
-7.6 (3)
-130.2 (2)
37.2 (2)
Results and Discussion
The structure of the crystal 4 is displayed in Fig. 1. The
˚
bond length in this compound of C(6)–C(7), 1.467(3) A;
123

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J Chem Crystallogr (2011) 41:514–518
˚
Table 3 Intermolecular interactions (A) in the compound 4
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D–HfꢀꢀꢀA
D–H
HꢀꢀꢀA
DꢀꢀꢀA
D–HꢀꢀꢀA
O(1)–H(1A)ꢀꢀꢀN(3)i
0.82
0.93
2.01
2.55
2.800 (3)
3.042 (3)
161
113
C(1)–H(1B)ꢀꢀꢀN(1)
i
2-x, 1-y, 1-z
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The dihedral angle between the plane (C7–C8–C11–N4)
and the benzene ring plane (C1–C6) is 140.58; the benzene
ring plane (C12–C17) is 118.28; the benzene ring plane
(C18–C23) is 128.28, the benzene ring plane (C25–C30) is
14.48; the plane (S1-C24–N5–O1) is 116.48,while the tri-
azole ring plane and the plane (C7–C8–C11–N4) is 117.58.
As seen from Fig. 1, the packing in this compound is
held together by O–HꢀꢀꢀN, C–HꢀꢀꢀN hydrogen bonds and
three C–HꢀꢀꢀCg (p-Ring) (Table 3). In addition, the exis-
tence of weak p–p stacking interaction is observed between
triazole and benzene ring (C12–C17). The distance
between the centrality of interacting ring is Cg (1)ꢀꢀꢀCg
˚
(3) = 3.9185(17) A (1 ? x, y, z). [Cg (1) = center
of gravity of the 1,2,4-triazole ring; Cg (3) = center of
gravity of the benzene ring (C12–C17)].The existence of
H-bonding and weak p–p stacking interaction in the
molecular structure is great helpful to stabilize the crystal
packing.
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Acknowledgments The authors specially thank the financial sup-
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20662009).
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