Synthesis and crystal structure of compound 1,5-bis(4-methoxyphenyl)-3a-(2- phenyl-2H-1,2,3-triazol-4-yl)-4,5-dihydro-3aH-benzo[b][1,2,4]oxadiazolo[4,5-d] [1,4]thiazepine

Article abstract of DOI:10.1007/s10870-007-9269-7

The crystal structure of title compound has been determined. The compound crystallizes in the triclinic system with space group P-1, lattice parameters; a = 9.2938 (5) A, b = 11.9992 (7) A, c = 25.5918 (13) A, α = 91.343 (2)°, β = 95.8360 (10)°, γ = 101.005 (2)°, V = 2784.3 (3) A³, Z = 4, X-Ray analysis reveals that the molecular backbone consists of tricyclic system with the central seven-membered ring in twisted chair-like conformation. The crystal structure of 1,5-bis(4-methoxyphenyl)-3a-(2-phenyl-2H-1,2,3-triazol-4-yl)-4,5-dihydro-3aH- benzo[b][1,2,4]oxadiazolo[4,5-d][1,4]thiazepine was first determined by single-crystal X-ray diffraction which reveals that the molecular backbone consists of a tricyclic system with the central seven-membered ring in twisted chair-like conformation.

Full text of DOI:10.1007/s10870-007-9269-7

J Chem Crystallogr (2008) 38:97–101
DOI 10.1007/s10870-007-9269-7
ORIGINAL PAPER
Synthesis and Crystal Structure of Compound 1,5-bis
(4-methoxyphenyl)-3a-(2-phenyl-2H-1,2,3-triazol-4-yl)-
4,5-dihydro-3aH-benzo[b][1,2,4]oxadiazolo[4,5-d][1,4]thiazepine
De-Bao Yang Æ Fang-Ming Liu Æ Feng Xu Æ
Chun Yang
Received: 30 July 2007 / Accepted: 4 October 2007 / Published online: 19 October 2007
ꢀ Springer Science+Business Media, LLC 2007
Abstract The crystal structure of title compound has
been determined. The compound crystallizes in the triclinic
system with space group P-1, lattice parameters;
2,3-triazole derivatives also show various biological effects,
certain compounds having a 1,2,3-triazole fragment have
been reported as antibacterials, antifungals, antivirals, anti-
inflammatories and analgesics and 1,2,3-triazole derivatives
have been synthesized to inhibit tumor proliferation,
invasion, metastasis, and have shown anti-HIV activity.
The importance and utility of benzothiazepines have led to
the development of numerous synthetic routes. Among the
various types of synthesized derivatives, 2,4-diaryl-2,3-dihy-
dro-1,5-benzothoazepines constitute an important group.
They are usually prepared by cyclocondensation of 2-ami-
nothiophenol(o-ATP) with a,b-unsaturated ketones in the
presence of a catalytic amount of acid [6] or under neutral
conditions [7, 8]. A series of studies of 1,5-benzothoazepines
have been carried out. However, [1,5]benzothiazepines
containing heterocyclic ring substituted at 4-position were
scarcely reported, and in order to extend the research depth of
the 1,5-benzothiazepine skeleton, we designed the synthetic
route for preparation of the target compound which is outlined
in Scheme 1 and the crystal structure of 1,5-bis(4-methoxy-
phenyl)-3a-(2-phenyl-2H-1,2,3-triazol-4-yl)-4,5-dihydro-3aH-
benzo[b][1,2,4]oxadiazolo[4,5-d][1,4]thiazepine was first
determined by single-crystal X-ray diffraction.
˚
a = 9.2938 (5) A, b = 11.9992 (7) A, c = 25.5918 (13) A,
˚
˚
a = 91.343 (2)ꢁ, b = 95.8360 (10)ꢁ, c = 101.005 (2)ꢁ,
3
V = 2784.3 (3) A , Z = 4 , X-Ray analysis reveals that the
˚
molecular backbone consists of tricyclic system with the
central seven-membered ring in twisted chair-like
conformation.
Keywords 1,5-Benzothiazepine Á 2-Phenyl-
1,2,3-triazole Á 1,2,4-Oxadiazole Á Crystal structure
Introduction
Over the past 20 years, synthesis of benzothiazepine has
been of considerable interest, due to the broad spectrum of
biological activities of this type of compounds.
Seven-membered ring analogous benzothiazepine
derivatives exhibit diverse biological activities as calcium
antagonists [1], angiotensin converting enzyme inhibitors
[2], anticonvulsand and tranguillzing agents [3], potential
anticancer drugs [4], and as endogenous natriuretic
factors [5].
Compounds containing the 1,2,3-triazole ring system are
well known for its high activity. However, the 2-phenyl-1,
Experimental
Synthesis of the Title Compound
Synthesis of Compound 1[9]
D.-B. Yang Á F.-M. Liu (&) Á C. Yang
College of Materials and Chemical Engineering, Hangzhou
Normal University, Hangzhou 310036, P.R China
e-mail: fmliu859@sohu.com
2-p-MethyloxyPhenyl-4-(2-phenyl-1,2,3-triazole-4-yl)-2,3-di-
hydro[1,5]benzothiazepine To a solution of chalcone
(4.0 mmol, 1.224 g) in ethanol (60 ml) was added o-ami-
nothiophenol (4.0 mmol, 0.5 g). The mixture was heated
F.-M. Liu Á F. Xu
College of Chemistry and Chemical Engineering, Xinjiang
University, Wulumuqi 830046, P.R. China
123

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J Chem Crystallogr (2008) 38:97–101
OCH3
Scheme 1 Preparation of the
title compound
N
N
SH
O
C
S
N
CF3COOH
reflux
N
C
H
C
H
OCH3
+
NH2
N
N
N
OCH3
1
Cl
S
H3CO
C N OH
N
N
N
N
O
N
H3CO
2
under reflux for 20-30 minutes and then added (1.2 ml) of
CF3COOH. The refluxing 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 was filtered, washed with
2–3 ml of cold aq ethanol and dried. The compound was
recrystallized from ethanol (compound 1), m.p.: 150–151 ꢁC.
on Agilent 5975 mass selective detector. Element analyses
for C, H were performed on a Perkin–Elmer 240C
analyzer.
Compound(1)
IR: (KBr)t cm–1, 3419, 3131, 2901, 1620, 1509, 1454,
Synthesis of Compound 2
1241. 70 ev MS m/z(%): 412(M+), 379, 278, 134(100%),
1
119, 108, 91. H-NMR (400 MHz,CDCl3) d: 8.53 (s, 1H,
1,5-Bis(4-methoxyphenyl)-3a-(2-phenyl-2H-1,2,3-triazol-
4-yl)-4,5-dihydro-3aH-benzo[b][1,2,4]oxadiazolo[4,5-d]
[1,4]thiazepine [10, 11] p-Methyoxylbenzohydroximi-
noyl chloride (1.5 mmol, 0.278 g) was added under stirring
to a solution of appropriate 1,5-benaothiazepine derivative
(1 mmol, 0.412 g) in (30 ml) of methylene chloride and a
solution of triethylamine (1.5 mmol, 0.151 g) in the same
solvent (5 ml) was added dropwise slowly. The reaction
mixture was kept under stirring at room temperature for
4 days. After completion of the reaction, the solvent was
evaporated off at reduced pressure, and ether was added to
the residue and the triethylamine hydrochloride was
filtered. After removal of the solvent, the residue was
purified by silica gel column chromatography with ethyl
acetate/light petroleum (V:V = 1:8). A colorless crystal
cultured from ethyl acetate and light petroleum
(V:V = 1:8) (compound 2), m.p: 202.7–203.9.
Triazole-H), 8.15–6.80 (m, 13H, Ar-H), 5.18–5.13 (dd,1H,
H-2, Jax = 4.8 Hz, Jbx = 12.0 Hz ), 3.79 (s, 3H, –OCH3),
3.70–3.65 (dd, 1H, H-3a, Jax = 4.80 Hz, Jab = 12.40 Hz),
3.08–3.01(dd, 1H, Jbx = 12.0 Hz, Jab = 12.40 Hz). Anal.
Calcd. (%) for C24H20N4OS: C, 69.88; H, 4.87; N, 13.58.
Found (%) C, 69.81; H, 4.87; N, 13.61.
Compound(2)
IR: (KBr)t cm–1, 3059, 2903, 1598, 1507, 1453, 1352,
1244, 657. 70 ev MS m/z(%):561(M+), 427, 399, 305, 278,
256, 172 (100%),134,117, 91, 77.1H-NMR (400 MHz,
CDCl3) d: 8.17(s, 1H, Triazole-H), 8.00–6.72 (m, 17H, Ar-
H), 4.65–4.60 (dd, 1H, H-x, Jax = 5.25 Hz, Jbx = 12.01
Hz), 3.84 (s, 3H, oxadiazoloph-OCH3), 3.78(s, 3H, ph-
OCH3) 3.41–3.35(dd, 1H, H-a, Jax = 5.25 Hz, Jab =
16.01 Hz), 3.29–3.23 (dd, 1H, H-b, Jbx = 12.01 Hz,
Jab = 16.01 Hz). Anal. Calcd. (%) for C32H27N5O3S:C,
68.45; H, 4.81; N, 12.47; S, 5.70. Found (%) C, 68.46; H,
4.82; N, 12.48; S, 5.71
Physical Measurements
Reagents and Apparatus
All purchased solvents and chemicals were of analytical
grade and used without further purification. 1H-NMR
spectra were measured with a Varian Mercury 400 MHz
using TMS as the internal standard at room temperature.
The solid-state IR spectra were recorded from KBr on a
Bruker Tensor27 spectrophotometer. MS were performed
X-ray Crystallography
The X-Ray diffraction data of the single crystal were
collected on
a crystal of approximate dimensions
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J Chem Crystallogr (2008) 38:97–101
99
Table 1 Crystal data and structure refinement for the title complex
Table 2 Selected bond lengths [Aꢁ] and bond angle [ꢁ]
CCDC deposition number
Formula
654171
32H26N5O3S
S1 C1
1.770(2)
1.834(2)
1.436(2)
1.460(2)
1.390(3)
1.419(3)
1.473(3)
1.287(3)
1.405(3)
1.523(3)
1.534(3)
1.521(3)
0.9900
C
S1 C7
Formula weight
560.64
O1 N2
Crystal size (mm)
Crystal colour
0.79 · 0.27 · 0.14
Colorless
Triclinic
O1 C9
N1 C10
Crystal system
N1 C6
Space group
P-1
N1 C9
Unit cell dimensions [Aꢁ] and angles (ꢁ)
˚
a (A)
N2 C10
9.2938(5)
11.9992(7)
25.5918(13)
91.343(2)
95.8360(10)
101.005(2)
2784.3(3)
4
C1 C6
˚
b (A)
C7 C25
˚
c (A)
C7 C8
a (ꢁ)
b (ꢁ)
c (ꢁ)
C8 C9
C8 H8A
C8 H8B
0.9900
˚
Volume (A 3)
C9 C17
1.510(3)
1.467(3)
105.62(9)
109.93(15)
124.68(17)
107.38(16)
121.77(17)
106.66(17)
123.47(15)
119.09(17)
113.17(14)
116.94(17)
108.1
Z
C10 C11
C1 S1 C7
N2 O1 C9
C10 N1 C6
C10 N1 C9
C6 N1 C9
C10 N2 O1
C6 C1 S1
C1 C6 N1
C8 C7 S1
C9 C8 C7
C9 C8 H8A
C7 C8 H8A
C9 C8 H8B
C7 C8 H8B
H8A C8 H8B
O1 C9 N1
O1 C9 C8
N1 C9 C8
N2 C10 N1
N2 C10 C11
N1 C10 C11
Density (calculated) (g/cm3)
1.337
Wavelength
0.71073
153(2)
Temperature
Absorption correction type
Absorption coefficient (l)
F(000)
Empirical
0.160
1172
Theta range for data collection
Index ranges
3.02ꢁ–27.48ꢁ
–12 £ h ‡ 11; –15
£ k ‡ 11; –33 £ l ‡ 33
26596/9424
Reflections collected/unique
R (int)
0.037
Completeness to theta = 27.48
96.9%
108.1
Absorption correction T (max), T (min) 0.9780; 0.8842
108.1
Refinement method
SHELXL
108.1
Data/restraints/parameters
Goodness of fit ref
12356/0/740
107.3
1.072
101.63(16)
106.43(16)
113.65(17)
114.24(19)
121.00(19)
124.56(18)
Final R indices [I [ 2.0 r(I)]
R indices (all data)
R1 = 0.0569, wR2 = 0.1417
R1 = 0.0730, wR2 = 0.1498
–3
–3
˚ ˚
0.84 e A and –0.48 e A
Largest diff. Pesk and hole
Fig. 1 The molecular structure
of the title compound. Thermal
ellipsoids have been drawn with
50% probability
123

100
J Chem Crystallogr (2008) 38:97–101
Fig. 2 Molecular packing arrangement in the unit cell
0.79 · 0.27 · 0.14 mm by using Rigaku R-axis Spider
diffractometer with graphite-monochromated MoK\a radi-
ation at 153(2) K. All calculation was carried out on a
computer with the aid of the SHELXS-97 [12] program and
refinements on ‘F2 were performed by full-matrix least-
squares techniques with equivalent isotropic displacement
parameters for the non-hydrogen atoms. A summary of the
crystallographic data and details of the structure refine-
ments are listed in Table 1.
is appreciable variation of the C–C and C–N bond lengths
depending upon whether the bond are within a five-, a six-
or a seven-membered ring or inter-ring.
˚
Therefore, in compound 2, the N(1)–C(10) (1,390(3) A),
˚
N(2)–C(10) (1,278(3) A), N(3)–C(18) (1,328(3) A) and
˚
˚
N(5)–C(17) (1,329(3) A) bonds are shorter than the
˚
N(1)–C(6) (1,419(3) A), N(1)–C(9) (1,473(3) A) and
˚
˚
N(4)–C(19) (1,423(3) A) bonds suggesting that the former
four bonds have somewhat higher bond orders that the
˚
latter three bonds. Expecting N(1)–C(9) (1.473(3) A) bond
˚
is approximately a normal C–N single bond (1.47 A), the
CCDC 654171 for the compound contains the supple-
mentary crystallographic data for this paper. This data can
be obtained free of charge from Cambridge Crystallo-
graphic Data Centre (CCDC)12 Union Road, Cambridge
CB2 1EZ, UK; phone: +44-1223-336408; fax: +44-1223-
336033; email: deposit@ccdc.cam.ac.uk; http://www.ccdc.
cam.ac.uk.
remanent six C–N bonds are substantially shorter than a
˚
normal C–N single bond (1.47 A) and all lie within the
range found in aromatic heterocycles, such as, pyridine,
adenine and guanosin [13].
Figure 1 is the stereo structure of compound 2. The
five–membered ring of oxadiazole in the molecule,
resulting from cyclo-addition reaction. All atoms N(1),
C(10),N(2), O(1) in the ring are nearly coplanar, and there
bond angles are similarly N(2) O(1) C(9) 109.93(15), C(10)
N(1) C(9) 107.38(16), C(10) N(2 )O(1)106.66(17), O(1)
C(9)N(1) 101.63(16), N(2) C(10 )N(1) 114.24(19),indi-
cating the ring is stable. The bond length of N(2)–C (10)
Results and Discussion
The structure of the title compound is shown in Fig. 1.The
selected bond lengths and bond angles are listed in
Table 2,respectively. The title compound consists of a
benzothiazepine ring, a 1,2,3-triazole ring and a oxadiazole
ring. The C–C and C–N bond lengths in the compound 2
suggest there is extensive delocalization with the fused
heterocyclic ring. However, with a given heterocycle there
˚
(1.278(3) A), indicating the N(2)–C(10) is a double bond.
The five-membered ring of oxadiazole adopts an
envelope coformation with the atom C(9) deviating from
the plane defined by N(1), C(10), N(2), O(1). There is a
123

J Chem Crystallogr (2008) 38:97–101
101
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seven-membered ring in the central of the compound 2, and
it is chair-like conformation. S(1), N(1), C(7), C(9) are
coplanar, C(1) and C(6) above the plane and C(8) below. In
view of literatures, we can know the a seven-membered
ring in the structure of compound is boat-like. So in this
reaction the conformation of the seven-membered ring has
changed from boat-like conformation in compound 1 to
chair-like in compound 2. However, the boat-like confor-
mation is more stable than the chair-like conformation
Fig. 2.
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refinement. University of Gottingen, Germany
13. Pauling L (1960) The nature of chemical bond, 3rd edn. Cornell
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Acknowledgements The authors gratefully acknowledge support
from the College of Materials and Chemical Engineering, Hangzhou
Normal University and Silicone key laboratories.
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