Synthesis and crystal structure of (2-chloro-4-(phenylthio)phenyl) (3-methyl-1-phenyl-5-(phenylthio)-1H-pyrazol-4-yl)methanone

Article abstract of DOI:10.1134/S002247661708025X

(2-Chloro-4-(phenylthio)phenyl)(3-methyl-1-phenyl-5-(phenylthio)-1H-pyrazol-4-yl)methanone was obtained by accident. In order to know the structure of this product, the compound was isolated by column chromatography and recrystallized from EtOH. The compo

Full text of DOI:10.1134/S002247661708025X

Journal of Structural Chemistry. Vol. 58, No. 8, pp. 1663-1667, 2017.
Original Russian Text © 2017 G.-X. Sun, Z.-W. Zhai, Z.-H. Sun, C.-X. Tan, J.-Q. Weng, X.-H. Liu.
SYNTHESIS AND CRYSTAL STRUCTURE
OF (2-CHLORO-4-(PHENYLTHIO)PHENYL)
(
3-METHYL-1-PHENYL-5-(PHENYLTHIO)-1H-
PYRAZOL-4-YL)METHANONE
1
G.-X. Sun , Z.-W. Zhai , Z.-H. Sun , C.-X. Tan ,
2
2
2
UDC 548.737
2 2
J.-Q. Weng , and X.-H. Liu *
(2-Chloro-4-(phenylthio)phenyl)(3-methyl-1-phenyl-5-(phenylthio)-1H-pyrazol-4-yl)methanone
was
obtained by accident. In order to know the structure of this product, the compound was isolated by column
chromatography and recrystallized from EtOH. The compound was characterized by X-ray diffraction. The
compound crystallized in the triclinic space group P-1 with a = 9.909(2) Å, b = 11.824(2) Å,
3
c = 13.056(3) Å, α = 63.309(3)°, β = 89.964(4)°, γ = 67.727(3)°, V = 1237.7(4) Å , Z = 2 and R = 0.0414.
DOI: 10.1134/S002247661708025X
Keywords: aryl sulfide, synthesis, crystal structure.
INTRODUCTION
Nowadays, sulfur chemistry has received considerable attention because of their medicinal, pesticidal, and industrial
importance [1-5]. Thioether derivatives (especially aryl sulfide) are important sulfur compounds [6-10] because they have
been widely used in pharmaceutical, polymer materials, flavor and fragrance. These compounds exhibit good biological
activities, such as herbicidal [11], GPR119 agonist [12], antiplatelet aggregation [13], antibacterial [14], anticancer [15],
antiviral [16] and are HIV-1 reverse transcriptase inhibitors [17]. For instance, pyrithiobac-sodium had been developed as
a commercial herbicide.
In view of these facts mentioned above, many references [18-20] reported the synthesis method for aryl sulfide.
Generally, aryl sulfide was synthesized from aryl halides and thiophenol under transition metal catalyst, such as Pd [21], Cu
[22], Co [23], Ni [24]. Recently, we have reported the synthesis of aryl sulfide using NaH/THF system [25]. As a part of our
work on the synthesis of bioactive lead compounds for drug discovery, a new aryl sulfide derivative was found through TLC.
1
In order to investigate the new structure of this aryl sulfide derivative, it was characterized by H NMR, MS, elemental
analysis, and X-ray diffraction.
1
School of Chemistry and Chemical Engineering, Yancheng Institute of Technology, Jiangsu, Yancheng,
2
P. R. China. College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, Zhejiang, P. R. China;
*
xhliu@zjut.edu.cn. The text was submitted by the authors in English. Zhurnal Strukturnoi Khimii, Vol. 58, No. 8, pp. 1713-
1717, November-December, 2017. Original article submitted November 19, 2015.
0022-4766/17/5808-1663 © 2017 by Pleiades Publishing, Ltd.
1663

RESULTS AND DISCUSSION
Synthesis. Intermediate 3 was synthesized from start material 1 and 2,4-dichloro phenyl acyl chloride by the base-
catalyzed method reported by Wu et al. [26] for the successful preparation of intermediate 3. In this paper, intermediate 3 was
synthesized in the presence of K
2 3
CO catalyst and 1,4-dioxane at the reflux for 2-3 h with a high yield. Then intermediate 3
3
reacted with POCl to give intermediate 4. Thioether intermediate 5 was synthesized by treating intermediate 4 with
benzenethiol under basic conditions at room temperature for 24 h, as shown in Scheme 1. Interestingly, in the KOH/DMF
system, two products were obtained. One was recognized as the title compound (2,4-dichlorophenyl)(3-methyl-1-phenyl-5-
(
phenylthio)-1H-pyrazol-4-yl)methanone, the other one is (2-chloro-4-(phenylthio)phenyl)(3-methyl-1-phenyl-5-
phenylthio)-1H-pyrazol-4-yl)methanone that was produced by double coupling, and its structure was characterized by single
(
crystal X-ray diffraction. When the NaH/THF system was tried in this procedure, it worked well and yielded one product 5a
in our experiment (Table 1).
Crystal structure. The selected bond lengths and bond angles are listed in Table 2. The molecular structure of the
title compound is shown in Fig. 1.
From Fig. 1 it is seen that the title compound consists of one pyrazole ring, four benzene rings, two thioether bonds,
and one carbonyl group. Generally, the average bond lengths and bond angles of pyrazole and phenyl rings are in normal
ranges [27-36]. In the pyrazole ring, the C9–N2 bond (1.321(3) Å) is significantly longer than the C=N bond (1.27 ∼ 1.28 Å)
[37, 38]. Meanwhile, the C7–N1 bond (1.356(2) Å) is shorter than the C–N bond (1.52 Å), which indicates significant
electron delocalization in the pyrazole ring system. The bond angles of two thiother bonds are 104.05(10)° (C7–S1–C11) and
102.34(11)° (C21–S2–C24) respectively. The C8–C17–C18 torsion angle is 129.98(18)°.
As shown in Fig. 1, the pyrazole ring is nearly vertical with two benzene rings with dihedral angles (θ) of 80.5° and
2.9° respectively. The pyrazole ring (N1, N2, C9, C8, C7) and two benzene rings (C11 to C16, C18 to C23) are fairly planar
8
TABLE 1. Products Obtained under Different Conditions
Entry
1
Reaction condition
NaH/THF
Compound
Entry
2
Reaction condition
KOH/DMF
Compound
5a
5a and 5b
TABLE 2. Selected Bond Lengths (Å) and Angles (deg.) for the Title Compound
Bond
X-ray crystal
Bond
X-ray crystal
Bond
X-ray crystal
S(1)–C(7)
1.751(2)
1.769(2)
1.776(2)
1.782(2)
1.739(2)
1.220(2)
1.356(2)
N(1)–N(2)
N(1)–C(1)
N(2)–C(9)
C(1)–C(2)
C(1)–C(6)
C(7)–C(8)
C(8)–C(9)
1.366(2)
1.438(3)
1.321(3)
1.377(3)
1.378(3)
1.400(3)
1.421(3)
C(8)–C(17)
C(9)–C(10)
C(11)–C(16)
C(17)–C(18)
C(18)–C(23)
C(24)–C(25)
1.462(3)
1.498(3)
1.379(3)
1.510(3)
1.381(3)
1.378(4)
S(1)–C(11)
S(2)–C(21)
S(2)–C(24)
Cl(1)–C(23)
O(1)–C(17)
N(1)–C(7)
Angle
X-ray crystal
Angle
X-ray crystal
Angle
X-ray crystal
C(7)–S(1)–C(11)
C(21)–S(2)–C(24)
C(7)–N(1)–N(2)
C(7)–N(1)–C(1)
N(2)–N(1)–C(1)
C(9)–N(2)–N(1)
C(2)–C(1)–C(6)
104.05(10)
102.34(11)
112.27(16)
129.96(17)
117.70(16)
105.52(16)
121.7(2)
C(2)–C(1)–N(1)
C(1)–C(2)–C(3)
N(1)–C(7)–C(8)
N(1)–C(7)–S(1)
C(8)–C(7)–S(1)
C(7)–C(8)–C(17)
N(2)–C(9)–C(8)
120.2(2)
118.3(3)
C(8)–C(9)–C(10)
C(16)–C(11)–S(1)
C(13)–C(12)–C(11)
O(1)–C(17)–C(8)
C(23)–C(18)–C(19)
C(22)–C(21)–S(2)
129.54(19)
124.62(17)
119.5(3)
106.18(17)
120.40(15)
132.81(15)
129.98(18)
111.34(18)
120.90(19)
118.24(19)
117.72(18)
1664

Fig. 1. Molecular structure of the title compound.
with
plane
equations
6.548x + 0.805y + 7.025z = 5.2853,
5.592x + 11.535y + 4.501z = 14.9192
and
6.395x + 10.902y + 2.154z = 11.0094 respectively. As for the benzene ring (C1 to C6) connected to the pyrazole ring, it is
also vertical with the other two benzene rings (C11 to C16 and C18 to C23). The dihedral angles (θ) are 87.1° and 97.8°
respectively. However, among them, the two benzene rings are nearly parallel with a dihedral angle (θ) of 11.3°. The benzene
ring (C24 to C29) held a certain twist angle with the other rings (41.0°, 56.2°, 64.1°, and 37.3°). In addition, the length of the
S(1)⋯Cl(1) contact (3.853 Å) allows for a specific interaction due to electronic factors. The latter interaction also contributes
to the stabilization of the observed molecular conformation, especially for the parallel between the two benzene rings (C11 to
C16, C18 to C23) [39].
EXPERIMENTAL
1
Instruments. Melting points were determined using an X-4 apparatus and were uncorrected. H NMR spectra were
3
measured on a Bruker AV-400 instrument using TMS as the internal standard and CDCl as the solvent. Elemental analyses
were performed on a Vario EL elemental analyzer. Crystallographic data on the compound were collected on a Rigaku Saturn
diffractometer. All the reagents are of analytical grade or freshly prepared before the use.
General procedure. The synthesis procedure of title compound was outlined in Scheme 1. Intermediates 1, 2, 3, 4
2
were synthesized according to our previous work [25]. Preparation of 5b: to a mixture of KOH (69 mmol) in H O (5 ml)
a thiophenol solution (63 mmol) in DMF (80 ml) was added dropwise at 45 °C. After being stirred for 1 h, the mixture was
added dropwise to a solution of intermediate 4 (60 mmol). The mixture was further stirred at 80 °C for 5 h, then water
(
25 mL) was added and extracted with ethyl acetate (3×15 mL). The organic layers were combined and dried over anhydrous
Na SO . The solvent was evaporated in vacuo and the residue was purified by column chromatography and recrystallized
from EtOH to give compound 5b. White yellow crystals, yield 48%, m.p. 128-131 °C; H NMR (CDCl
2
4
1
3
, 400 MHz), δ: 7.56
(
s, 1H, Ph–H), 7.30-7.39 (m, 6H, Ph–H), 7.18-7.25 (m, 6H, Ph–H), 6.67-6.71 (m, 3H, Ph–H), 6.66 (m, 2H, Ph–H), 2.53 (s,
+
H, pyrazol-CH ). MS (ESI), m/z: 514(M+1) .
3
3
Elemental analysis. For C29
Structure determination. A cube-shaped single crystal of the title compound was obtained by recrystallization
from EtOH. The crystal with dimensions of 0.24×0.20×0.18 mm was mounted on a Rigaku Saturn diffractometer with
graphite-monochromated MoK radiation (λ = 0.71073 Å) and analyzed using ϕ scan modes at 294(2) K in the range
.01 ≤ θ ≤ 26.44°. A total of 5808 reflections were collected, out of which 5003 were independent (Rint = 0.0162) and 3475
2 2
H21ClN OS calculated, %: C 67.89, H 4.13, N 5.46; found: C 67.90, H 4.17, N 5.65.
α
2
were observed with I > 2σ(I). The calculations were performed using the SHELXS-97 program [40, 41] and the empirical
absorption corrections were applied to all intensity data. The non-hydrogen atoms were refined anisotropically. The hydrogen
1665

Scheme 1. The synthetic route of title compound.
atoms were determined by theoretical calculations and refined isotropically. The final full-matrix least squares refinement
2
2
gave R = 0.0414 and wR = 0.1038 (w = 1/[σ (F ) + (0.056P) + 0.3781P] where P = ( F + 2F )/3), S = 1.02,
2
2
2
0
0
c
1
Δ/σ)max = 0.003, Δρmax = 0.39 and Δρmin = –0.30 e/Å .
(
CONCLUSIONS
In summary, the crystal and molecular structure of the title compound (2-chloro-4-(phenylthio)phenyl)(3-methyl-1-
phenyl-5-(phenylthio)-1H-pyrazol-4-yl)methanone is reported. These data represent a crystallographically characterized
example of a molecular compound. This synthetic method can be applied in building blocks of dithioether compounds.
This work was supported by the public program of Science and Technology Department of Zhejiang Province
(2013C32SA700134, 2014C31127) and the program of Science and Technology of Jiangsu Province (BY2014108-14). Also
we thank the Dr. J. Wu to help the crystal.
Crystallographic data for the structure reported in this article have been deposited with the Cambridge
Crystallographic Data Center, CCDC 1453985. Copies of this information may be obtained free of charge from the Director,
CCDC, 12 Union Road, Cambridge, CBZ IEZ, UK. Facsimile (44) 01223 336 033, E-mail: deposit@ccdc.cam.ac.uk or
http//www.ccdc.com.ac.uk/deposit.
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