Synthesis and crystal structure of compound 1-phenyl-2-(1H-1,2,4-triazolo- yl)-3-phenyl-propen-1-one and 1-diphenyl-3-(1,2,4-triazolo-yl)-1H,4H-1,5- benzothiazepine

Article abstract of DOI:10.1007/s10870-010-9906-4

The crystal structures of the compounds 1-phenyl-2-(1H-1,2,4-triazolo-yl)- 3-phenyl-propen-1-one (2), and 2,4-diphenyl-3-(1,2,4-triazolo-yl)-1H,4H-1,5- benzothiazepine (3) were obtained by single crystal X-ray diffraction. Compound 2 crystallizes in the t

Full text of DOI:10.1007/s10870-010-9906-4

J Chem Crystallogr (2011) 41:485–490
DOI 10.1007/s10870-010-9906-4
ORIGINAL PAPER
Synthesis and Crystal Structure of Compound 1-Phenyl-
2-(1H-1,2,4-triazolo-yl)-3-phenyl-propen-1-one and 1-Diphenyl-
3-(1,2,4-triazolo-yl)-1H,4H-1,5-benzothiazepine
•
Sheng-Qin Chen Fang-Ming Liu
Received: 25 January 2010 / Accepted: 17 November 2010 / Published online: 8 December 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The crystal structures of the compounds 1-phenyl-
2-(1H-1,2,4-triazolo-yl)-3-phenyl-propen-1-one (2), and 2,
4-diphenyl-3-(1,2,4-triazolo-yl)-1H,4H-1,5-benzothiazepine (3)
were obtained by single crystal X-ray diffraction. Compound
2 crystallizes in the triclinic system with space group P - 1,
membered rings [3]. Benzothiazepine compounds have
confirmed known, bioactivity bioactivities, and many
papers discussing the synthesis, structure–property rela-
tionships and the applications of such compounds have
been published [4]. It has been reported that compounds
bearing benzothiazepine moieties have shown anti-HIV
[5], anti-hypertensive [6], anti-depressant [7], and anti-
bacterial activity [8]. For instance, the drug diltiazem,
which elicits anti-hypertensive effect, contains ben-
zothiazepine as its structural subunit [9].
˚
˚
˚
a = 8.5553(17) A, b = 9.6229(19) A, c = 9.924(2) A, a =
3
˚
106.16(3)°, b = 108.03(3)°, c = 105.14(3)°, V = 690.1(2) A ,
Z = 2. The compound 3 crystallizes in the orthorhombic
˚
system with space group Pbca, a = 12.904(3) A, b =
˚
˚
15.864(3) A, c = 19.140(4) A, a = 90°, b = 90°, c = 90°,
3
˚
V = 3918.3(14) A , Z = 8. H-bonds and p–p stacking are
In addition, 1H-1,2,4-triazole derivatives represent an
interesting class of heterocycles. Compounds containing
1H-1,2,4-triazole moiety have received considerable
attention among medicinal chemists because molecules
with these structural features have been found to show a
broad range of potent biological activities, such as anti-
hypertensive, antifungal [10] and antibacterial [11]. Com-
pounds containing the 1H-1,2,4-triazole ring system are
also well known to be highly active as fungicides [12],
especially on the Basidiomycete and Ascomycete groups of
fungi. In view of these facts and in order to search for new
fused heterocyclic compounds with improved bioactivity,
the present investigation deals with the synthesis of novel
benzothiazepine system bearing 1,2,4-triazole moiety, as
outlined in Scheme 1, which might have useful biological
and therapeutic activities. The crystal structures of 2 and 3
determined by single-crystal X-ray diffraction are reported.
the main non-bonding interactions in the molecular struc-
ture. Details of the synthesis, structures, and spectroscopic
properties of the two compounds are discussed.
Keywords 1,2,4-triazole Á Benzothiazepine Á Crystal
structure
Introduction
Since biological and pharmacological activities have been
noted for great number of heterocyclic aromatic cycles [1,
2], much attention has been paid to the synthesis of the
heterocyclic compounds incorporating one or more seven
S.-Q. Chen Á F.-M. Liu (&)
College of Materials and Chemical Engineering, Hangzhou
Normal University, Hangzhou 310036,
People’s Republic of China
Experimental
e-mail: fangmingliu895@yahoo.com.cn
Reagents and Apparatus
F.-M. Liu
College of Chemistry and Chemical Engineering, Xinjiang
University, Urumqi 830046, People’s Republic of China
All reagents were of commercial availability. Reactions
were monitored by thin-layer chromatography (TLC).
123

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J Chem Crystallogr (2011) 41:485–490
O
N
internal standard. EI-ms spectra were recorded with an
Agilent 5975 apparatus. X-ray crystal structures were
obtained using R-AXIS SPIDER X-ray diffraction.
O
C
HN
O
C
HC
N
H2
C
N
CH2Br
N
Et3N
N
Piperidine
1
The Synthesis of a-Phenyl-2-(1H-1,2,4-triazolo-yl)
ethanone 1
SH
O
S
N
NH2
N
N
N
N
N
Intermediate 1 was prepared according to the reported
method [13].
N
H
Compound 1: White crystals, Yield 65.92%,
m.p.121.4–122.4 °C.
2
3
Scheme 1 Synthetic process of the title compound
The Synthesis of 1-Phenyl-2-(1H-1,2,4-triazolo-yl)-
3-phenyl-prop-en-1-one 2
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 ele-
mental analyzer. The IR spectra were determined using
potassium bromide pellets on a Bruker Equinox 55 FT-IR
The procedure according to the literature [14].A solution of
benzaldehyde (0.02 mol), a-aryl-2-(1H-1,2,4-triazolo-1yl)
ethanone(0.02 mol), and piperidine (0.5 mL) in toluene
(80 mL) was refluxed for 7 hunder nitrogen atmosphere and
during that time, the generated water was removed with a
1
spectrophotometer. The HNMR spectra were recorded on
a Varian Inova-400 spectrophotometer using TMS as an
Table 1 Summary of structure determination of compounds 2 and 3
CCDC deposition number
Formula
762788
762789
C17H15N3O
277.32
C23H17N4S
381.47
Formula weight
Crystal size(mm)
Crystal colour
0.690 9 0.580 9 0.270
Colorless
0.691 9 0.374 9 0.060
Colorless
Crystal system
Triclinic
Orthorhombic
Pbca
Space group
P - 1
Unit cell dimensions [A°] and angles (°)
˚
a (A)
8.5553 (17)
9.6229 (19)
9.6229 (19)
9.6229 (19)
9.6229 (19)
9.6229 (19)
690.1 (2)
2
12.904 (3)
15.864 (3)
19.140 (4)
90
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
90
90
3
˚
Volume (A )
3918.3 (14)
8
Z
Density (calculated) (Mg/m3)
Absorption coefficient (l)
F(000)
1.335
1.293
0.086
0.181
292
1592
Theta range for data collection
Index ranges
3.57–25.03°
-10 B h B 10, -11 B k B 9, -11 B l B 11
3.16–25.03°
-15 B h B 15, -18 B k B 18, -22 B l B 22
Reflections collected/unique
R(int)
5425/2423
27623/3461
0.0425
0.0921
Absorption correction T(max), T(min)
Refinement method
Goodness of fit ref
0.9769; 0.9428
Full-matrix least-squares on F2
0.9513; 0.9085
Full-matrix least-squares on F2
1.100
1.017
Final R indices [I [ 2.0 r(I)]
R indices(all data)
R1 = 0.0507, wR2 = 0.1511
R1 = 0.0574, wR2 = 0.1578
R1 = 0.0625, wR2 = 0.1513
R1 = 0.1124, wR2 = 0.1770
-3
-3
˚
0.162 and -0.512 e A
˚
0.309 and -0.339 e A
Largest diff. Pesk and hole
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J Chem Crystallogr (2011) 41:485–490
487
The Synthesis of Compound 2,4-Diphenyl-3-(1,2,
4-triazolo-yl)-1H,4H-1,5-benzothiazepine 3
Dean-Stark trap. After completion of the reaction, the sol-
vent was evaporated off at reduced pressure. The residue was
purified by silica gel column chromatography with ethyl
acetate/light petroleum (V:V = 1:1). A colorless crystal of
compound 2 was cultured from ethyl acetate and petroleum.
Compound 2: colorless crystals, Yield 76.2%; m.p.
129.8–130.6 °C, 1HNMR(CDCl3, 400 MHz) d: 8.192(s, 1H,
Triazole-H), 8.152(s, 1H, Triazole-H), 7.838(s, 1H, C=CH),
7.820 * 6.914 (m, 10H, Ar–H); IR(KBr) t: 3112, 3062
To a solution of chalcone (4.0 mmol) in methanol
(60 mL) was added o-aminothiophenol (4.0 mmol). The
reaction mixture was kept under stirring at room tem-
perature for 0.5 h.The mixture was heated under reflux for
20–30 min and then added CF3COOH (1.2 mL). 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 by filtered, washed by cold
methanol and dried. The crude compound was recrystal-
lized from methanol.
(Ar–H), 1647(C=O), 1499, 1447, 1419(C=N, C=C) cm-1
;
MS(EI) m/z(100%):275(M?), 247, 178, 146, 116,
105(100%), 77.
Anal.Calcd. for C17H15N3O: C, 74.17; H, 4.76; N,
15.26; O, 5.81; Found C, 15.28; H, 4.878; N, 15.28.
Fig. 1 a Molecular structure of
2. b Packing diagram of 2
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J Chem Crystallogr (2011) 41:485–490
Compound 3: Colorless crystals, Yield 72.7%. m.p.209–
X-ray Crystallography
211 °C. 1HNMR (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 C23H17N4S: C, 72.22; H, 4.74; N, 14.65;
Found C, 72.04; H, 4.817; N, 14.57;
The X-ray diffraction data of 2 and 3 were collected
on crystals of approximate dimensions 0.690 9 0.580 9
0.270 mm and 0.691 9 0.374 9 0.060 mm respectively
using a Rigaku R-axis Spider diffractometer with graphite-
monochromated MoKa radiation at 293(2) K. All calcula-
tions were carried out with the aid of the SHELXS-97 [15]
˚
Table 2 Selected bond lengths (A), bond angles (°), and torsion angles (°) for compound 2 and 3
˚
Compound 2 [bond lengths (A)]
N(1)–C(11)
N(1)–N(2)
N(1)–C(6)
O(1)–C(4)
C(3)–C(6)
N(3)–C(17)
1.339(2)
C(3)–C(8)
C(4)–C(6)
C(4)–C(7)
N(2)–C(17)
C(11)–N(3)
C(8)–C(10)
1.471(2)
1.491(2)
1.495(2)
1.304(2)
1.304(2)
1.399(2)
1.3517(18)
1.4340(18)
1.2172(18)
1.335(2)
1.343(3)
˚
Compound 3 [bond lengths (A)]
S(1)–C(6)
1.756(4)
1.835(3)
1.321(4)
1.367(3)
1.441(4)
1.394(4)
1.520(4)
N(1)–C(5)
N(3)–C(15)
N(4)–C(16)
N(4)–C(15)
C(7)–C(8)
1.417(4)
1.318(4)
1.315(4)
1.339(4)
1.502(4)
1.339(4)
1.373(6)
S(1)–C(7)
N(2)–C(16)
N(2)–N(3)
N(2)–C(8)
N(1)–C(23)
C(8)–C(23)
C(11)–C(12)
C(7)–C(9)
Compound 2 [bond angles (°)]
C(11)–N(1)–N(2)
C(11)–N(1)–C(6)
N(2)–N(1)–C(6)
109.21(14)
129.15(14)
121.56(13)
130.25(14)
124.83(14)
103.24(16)
114.94(17)
O(1)–C(4)–C(6)
O(1)–C(4)–C(7)
C(6)–C(4)–C(7)
C(3)–C(6)–N(1)
N(1)–C(6)–C(4)
C(17)–N(2)–N(1)
N(3)–C(11)–N(1)
119.19(15)
119.53(14)
121.23(14)
121.78(14)
113.32(13)
102.52(15)
110.07(17)
C(6)–C(3)–C(8)
C(3)–C(6)–C(4)
C(11)–N(3)–C(17)
N(2)–C(17)–N(3
Compound 3 [bond angles (°)]
C(6)–S(1)–C(7)
101.60(15)
128.5(3)
124.2(3)
121.5(3)
131.3(3)
128.1(3)
C(8)–C(7)–C(9)
C(8)–C(7)–S(1)
C(9)–C(7)–S(1)
C(23)–C(8)–N(2)
N(2)–C(8)–C(7)
C(8)–C(23)–C(17)
115.5(3)
113.3(2)
111.7(2)
116.5(3)
112.1(2)
121.7(3)
C(23)–N(1)–C(5)
C(6)–C(5)–N(1)
C(5)–C(6)–S(1)
C(23)–C(8)–C(7)
C(8)–C(23)–N(1)
Compound 2 [torsion angles (°)]
C(11)–N(1)–C(6)–C(3)
C(11)–N(1)–C(6)–C(4)
O(1)–C(4)–C(6)–C(3)
Compound 3 [torsion angles (°)]
C(23)–N(1)–C(5)–C(6)
N(1)–C(5)–C(6)–S(1)
C(7)–S(1)–C(6)–C(5)
C(5)–N(1)–C(23)–C(8)
116.8(2)
O(1)–C(4)–C(6)–N(1)
C(7)–C(4)–C(6)–C(3)
C(7)–C(4)–C(6)–N(1)
9.2(2)
-60.2(2)
9.6(2)
-167.72(15)
-173.40(12)
52.8(5)
C(6)–S(1)–C(7)–C(8)
S(1)–C(7)–C(8)–C(23)
C(7)–C(8)–C(23)–N(1)
S(1)–C(7)–C(8)–N(2)
69.5(2)
-2.3(4)
-59.6(3)
-24.8(5)
-28.8(4)
-4.7(6)
151.0(2)
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J Chem Crystallogr (2011) 41:485–490
489
Table 3
˚
Intermolecular interactions (A) in the compound 2
D–HÁÁÁA
D–H
HÁÁÁA
2.49
2.46
DÁÁÁA
3.029(2)
D–HÁÁÁA
117
C(10)–H(10A)ÁÁÁN(1)
0.93
0.93
C(16)–H(16A)ÁÁÁO(1)a
3.360(2)
164
˚
Intermolecular interactions (A) in the compound 3
D–HÁÁÁA
D–H
HÁÁÁA
2.31
2.93
DÁÁÁA
3.118(4)
D–HÁÁÁA
156
N(1)–H(1A)ÁÁÁN(4)b
0.86
0.93
C(10)–H(10A)ÁÁÁCg(2)c
3.651(4)
136
a
b
1 - x, 2 - y, 2 - z. 5/2 - x, 1/2 ? y, z. 2 - x, -1/2 ? y, 1/2 - z; Cg(2) is the center of gravity of ring C1–C6
c
Fig. 2 a Molecular structure of
3. b Packing diagram of 3
123

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J Chem Crystallogr (2011) 41:485–490
and PLATON [16], programs 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 refinements are listed in
Table 1.
N(1) and C(23) are above the plane, with their deviations
˚
being 0.5905, 0.2790 and 0.1674 A, respectively. Therefore,
according to the data, the seven-membered ring adopts a
boat-like conformation. The bond length in this ring of
˚
˚
C(23)–C(8), 1.339(4) A and C(7)–C(8), 1.502(4) A, indicates
it is a double bond between C(23) and C(8) (Table 2).
The dihedral angle between the benzene ring planes
(C1–C6) and the thiazepine ring planes (N1–C5–C6–S1–
C7–C8–C23) is 29.8°, while the angle is 67.8° between the
benzene ring plane (C1–C6) and triazole ring plane. In this
molecule, the packing in compound 3 is held together by a
N–HÁÁÁN hydrogen bond and a C–HÁÁÁCg (p-Ring). In
addition, weak p–p stacking interactions are observed
between triazole ring and benzene ring (C17–C22). The
distance between the centroids of interacting rings is
The X-ray data for compounds 2 and 3 respectively have
been deposited with Cambridge Crystallographic Data Centre
as CCDC 762788 and CCDC 762789. These 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.
˚
Results and Discussion
Cg(1)ÁÁÁCg(4) = 4.104(2) A (x, y, z) (Table 3). [Cg(1) =
center of gravity of the triazole ring; Cg(4) = center of
gravity of the benzene ring (C17–C22)]. The existence of
H-bonding and weak p–p stacking interaction in the
molecular structure is great helpful to stabilize the crystal
packing.
The molecular structure of the compound 2 is exhibited in
Fig. 1. The dihedral angle between the benzene ring plane
(C7–C16) and the plane (O1–C4–C6–C3) is 49.3°, the
plane (C8–C10) and the plane(O1–C4–C6–C3) is157.2°,
while the triazole ring plane and the plane (O1–C4–C6–C3)
is 61.5°. The bond length in this compound of C(3)–C(6),
Acknowledgements The authors thank the National Natural Sci-
ence Foundation of China (No: 20562011, 20662009) for financial
support.
˚
˚
˚
1.335(2) A, O(1)–C(4), 1.2172(18) A, C(4)–C(6), 1.491(2) A,
˚
˚
C(4)–C(7), 1.495(2) A and N(1)–C(6), 1.4340(18) A,
indicates it is a double bond between C(3) and C(6), as well
as O(1) and C(4) (Table 2). Besides, the data of above
suggests that the length of these two double bonds are
much longer than the corresponding length of the normal
double bond, and also demonstrates that the length of these
three single bonds are a little shorter than the correspond-
ing length of the normal single bond. In conclusion, there
is, predicatively, a conjugate system in this molecule. In
this molecule, the packing in this compound is held toge-
ther by C–HÁÁÁN, C–HÁÁÁO hydrogen bonds and three
C–HÁÁÁCg (p-Ring). In addition, existence weak p–p
stacking interactions between triazole and benzene ring
(C7–C16) of intermolecules are observed. The distance
between the centroids of interacting rings is Cg(1)ÁÁÁ
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The structure of the crystal 3 is displayed in Fig. 2.
There is a seven-membered ring in the molecule. 1,5-
Benzothiazepine ring is characterized by the endocyclic
torsion angles (enumerated clockwise and starting with
N(1)–C(5)–C(6)–S(1)): -2.3(4), 52.8 (5), -24.8(5), -4.7(6),
-28.8(4), 69.5(2), -59.6(3) (Table 2). The four atoms of
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123