Structural Characterization of a New Chalcone Compound Containing a Thiophene Moiety: (E)-3-(5-Bromothiophen-2-YL)-1- (2,5-Dichlorothiophen-3-YL)-2-Propen-1-One

Article abstract of DOI:10.1134/S0022476618060276

The crystal structure of the new chalcone derivative (E)-3-(5-bromothiophen-2-yl)-1-(2,5-dichlorothiophen- 3-yl)-2-propen-1-one is synthesized and structurally characterized by spectroscopic IR, NMR, and HRMS techniques. Its crystal and molecular structure is determined from the single crystal X-ray diffractionstudy. This compound crystallizes in the monoclinic system and space group P21/n (N 19). The crystal packing is governed by C—H..O non-conventional hydrogen bond-type intermolecular interactions, forming extended zigzag chains related by 21 screw axes running along the [010] direction, with graph-set C(8). These hydrogen bonds contribute to the stabilization of the crystal structure that packs with an efficiency of 71.4%.

Full text of DOI:10.1134/S0022476618060276

Journal of Structural Chemistry. Vol. 59, No. 6, pp. 1440-1445, 2018.
Original Russian Text © 2018 G. E. Delgado, J. A. Henao, J. H. Quintana, H. M. Al-Maqtari, J. Jamalis, H. M. Sirat.
STRUCTURAL CHARACTERIZATION OF A NEW
CHALCONE COMPOUND CONTAINING A THIOPHENE
MOIETY: (E)-3-(5-BROMOTHIOPHEN-2-YL)-1-
(
2,5-DICHLOROTHIOPHEN-3-YL)-2-PROPEN-1-ONE
1
G. E. Delgado , J. A. Henao , J. H. Quintana ,
2
2
3
H. M. Al-Maqtari , J. Jamalis , and H. M. Sirat
3
3
The crystal structure of the new chalcone derivative (E)-3-(5-bromothiophen-2-yl)-1-(2,5-dichlorothiophen-
-yl)-2-propen-1-one is synthesized and structurally characterized by spectroscopic IR, NMR, and HRMS
3
techniques. Its crystal and molecular structure is determined from the single crystal X-ray diffractionstudy.
This compound crystallizes in the monoclinic system and space group P21/n (N 19). The crystal packing is
governed by C---H⋯O non-conventional hydrogen bond-type intermolecular interactions, forming
extended zigzag chains related by 21 screw axes running along the [010] direction, with graph-set C(8).
These hydrogen bonds contribute to the stabilization of the crystal structure that packs with an efficiency of
71.4%.
DOI: 10.1134/S0022476618060276
Keywords: synthesis, chalcones, thiophene, crystal structure, hydrogen bond patterns.
INTRODUCTION
Chalcones (1,3-diaryl-2-propen-1-ones) are a class of compounds consisting of two aryl rings linked by an α,β-
unsaturated ketone moiety. Chalcones represent an essential group of natural as well as synthetic products and some of them
possess a wide range of pharmacological activities.
Heterocyclic chalcone derivatives show interesting and important properties against many of human diseases such as
anti-AIDS agents [1], anti-malarial [2], anti-inflammatory [3], anti-leishmanial [4], anti-oxidant [5], anti-cancer [6], and anti-
microbial [7].
These interesting compounds could be synthesized by several methods based on the formation of carbon-carbon
bonds. Claisen-Schmidt condensation has been used by many groups as a method for the synthesis of chalcone in the
presence of an aqueous alkaline base [8]. Other methods could also be used, including Friedel-Сrafts acylation [9], the Suzuki
coupling reaction [10], microwave irradiation [11], ultrasound irradiation [12], and the grinding technique [13].
In addition, chalcones have been used as an important intermediate compound in the synthesis of five- and six-
member rings [14] and as an intermediate in the biosynthesis of flavonoids [15].
1
Laboratorio de Cristalografía, Departamento de Química, Facultad de Ciencias, Universidad de Los Andes, Mérida,
2
Venezuela; gerzon@ula.ve. Grupo de Investigación en Química Estructural, Escuela de Química, Facultad de Ciencias,
3
Universidad Industrial de Santander, Bucaramanga, Colombia. Department of Chemistry, Faculty of Science, Universiti
Teknologi Malaysia, Johor, Malaysia. The text was submitted by the authors in English. Zhurnal Strukturnoi Khimii, Vol. 59,
No. 6, pp. 1493-1498, July-August, 2018. Original article submitted July 7, 2017.
1440
0022-4766/18/5906-1440 © 2018 by Pleiades Publishing, Ltd.

In this work we report the synthesis, spectroscopic characterization, and crystal structure of a new chalcone
derivative compound containing two thiophene rings, (E)-3-(5-bromo thiophen-2-yl)-1-(2,5-dichlorothiophen-3-yl)-2-propen-
1-one, among a series of chalcone thiophene derivatives as potential antimicrobial and anticancer agents [16].
EXPERIMENTAL
Synthesis. The title compound was synthesized by the Claisen-Schmidt condensation method [8] (Scheme 1) using
a methodology previously reported [16]. A solution of 2,5-dichlorothiophene (1) (100 mmol), acetyl chloride (2) (10 ml), and
carbon disulfide (10 ml) were mixed. Anhydrousaluminum chloride was slowly addedto the mixture during 15 min. The
reaction mixture was stirred at room temperature for overnight, and then cooled and poured into ice water. The carbon
disulfide layer was separated and washed three times with water and the solvent was removed to give solid 3-acetyl-2,5-
dichlorothiophene product (3). Yield 76.7%; m.p. 38-40 °C.
A mixture of 3 (0.03 mol) with 5-bromo-2-thiophenecarboxaldehyde (4) (0.03 mmol) was dissolved in methanol
(
25ml). Aqueous sodium hydroxide (15 ml) was added dropwise and the resulting mixture was stirred overnight at room
temperature. The precipitate was collected, dried, and purified by recrystallization from ethanol to give thiophene chalcone
E)-3-(5-bromothiophen-2-yl)-1-(2,5-dichlorothiophen-3-yl)-2-propen-1-one (5). Yellow needle-like crystals of 5 suitable for
(
the X-ray diffraction analysis were grown by slow evaporation in an ethanol solution. Yield: 83.6%; m.p. 100-102 °C.
Scheme 1. Synthesis of (E)-3-(5-bromothiophen-2-yl)-1-(2,5-dichlorothiophen-3-yl)-2-propen-1-one 5.
FT–IR, NMR, and HRMS analyses. Melting points were measured on a Leica Gallen III Kofler micro melting
1 13
points apparatus. Infrared (IR) spectra were recorded on a Perkin Elmer FT-IR spectrometer. H and C NMR spectra were
recorded on a BrukerAvance II spectrometer using deuterated DMSO and CDCl as solvents. Mass spectra were obtained
3
from NUS Mass Spectrometry Service, Singapore.
–
1
2
3) IR νmax, cm : 3102 (C–H sp ), 3003 (C–H sp ), 1659 (C=O); H–NMR (DMSO): δ 2.50 (3H, s) and δ 7.53
3
1
(
(1H, s).
–1 1
5) IR νmax, cm : 3078 (Ar–H), 1644 (C=O), 1579, 1512 (Ar–C=C), C–Cl (1020); H NMR (CDCl ): δ 7.07(1H, d,
(
3
J = 4 Hz, H-5), δ 7.08 (1H, d, J = 15.2 Hz, H-2), δ 7.12 (1H, d, J = 4 Hz, H-6), δ 7.19 (1H, s, H-11), δ 7.76 (1H, d,
13
J = 15.2 Hz, H-3); C NMR (CDCl ): δ 117.20 (C-7), δ 122.56 (C-5), δ 127.08 (C-11), δ 127.12 (C-8), δ 131.28 (C-9), δ
3
1
3
31.49 (C-2), δ 132.86 (C-6), δ 136.61 (C-3), δ 137.60 (C-10), δ 141.61 (C-4), δ 182.84 (C-1; Found (HRMS–ESI):
+ +
88.8247 [M+Na] and 389.8280 [M+H+Na] , (C H BrCl OS requires, 388.8240 and 389.8318).
11
5
2
2
1 13
The chemical structure of 5 was determined using H NMR, C NMR, andATR-FTIR. For chalcone 5, H-2 and H-3
showed a doublet peak which has a big coupling constant of 15.2 Hz. Protons at 5 and 6 carbon atoms also gave a nice
doublet with a small coupling constant of 4.0 Hz. Meanwhile, due to no neighboring proton at H-11, it appeared as a singlet
13
peak at δ7.19. The structure of the product was confirmed from the C NMR spectra where the carbon atom belonging to the
carbonyl group (C=O) gave rise to peaks in the most downfield region of the spectrum at δ182.84. It also showed the
presence of eight aromatic carbon atoms that suit the proposed structure of chalcone 5. The presence of the product was also
–1 –1
proven using ATR–FTIR spectroscopy where Ar–H, C=O and C=C aromatic absorption bands at 3078 cm , 1644 cm , and
–1
1512 cm respectively were observed. The ATR-FTIR spectrum of chalcone 5 also showed the presence of the C–Cl
–1
stretching vibration in the region of 1020 cm indicating the presence of a chlorine atom in the compound.
1441

Single crystal X-ray crystallography. A colorless rectangular crystal (0.07 mm, 0.10 mm, 0.32 mm) was used for
data collection. Diffraction data were collected at 295(2) K by the ω-scan technique on a Rigaku Pilatus 200 K diffractometer
α
with MoK radiation (λ = 0.71073 Å). The data were corrected for the Lorentzpolarization and absorption effects [17]. The
structure was solved by direct methods using the SHELXS program [18] and refined by a full-matrix least-squares calculation
2
on F using SHELXL [19]. All H atoms were placed at the calculated positions and treated using the riding model, with C–H
distances being 0.97-0.98 Å. The U (H) parameters were fixed at 1.2U (C). Table 1 summarizes the crystal data, intensity
iso eq
data collection, and refinement details for the title compound.
CCDC-1447773 contains the supplementary crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
RESULTS AND DISCUSSION
All spectral data (IR, NMR, and HRMS) obtained were consistent with the structure assigned and confirmed the
molecular skeleton. The title compound crystallizes in the centrosymmetric space group P2 /n. Fig. 1 shows the molecular
1
structure and the atom labeling scheme of 5 generated using the Diamond program [20]. All geometrical calculations were
made using the Platon program [21]. Selected bond distances, bond angles and torsion angles are presented in Table 2.
Title compound 5 crystallizes with one molecule in the asymmetric unit, in which the structure shows two thiophene
rings linked by a prop-2-en-1-one group. The molecule exists in the E configuration with respect to the central prop-en-one
group defined by the C5–С6–С7–С8 torsion angle of –179.8(4)°. It should be noted that both cis and trans isomeric forms
have been observed in 1,3-diarylprop-2-en-1-ones, but the trans isomer is thermodynamically more stable [22].
A search of the Cambridge Structural Database (CSD, version 5.37, May, 2016) [23] revealed four related structures
with 2,5-dichlorothiophene fragments and 14 entries with 5-bromo-2-thiophene fragments. All bond distances and angles are
in agreement with the experimental average values found for similar structures, as in 3-acetyl-2,5-dichlorothiophene
(KUYXEI) [24], (E)-1-(2,5-dichloro-3-thienyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one (KUYXAE) [25], (E)-1-(2,5-
dichloro-3-thienyl)-3-[4-(dimethyl amino)phenyl]prop-2-en-1-one (NUQKUG) [26], and (2E)-1-(2,5-dichloro-3-thienyl)-3-
(6-methoxy-2-naphthyl)prop-2-en-1-one (QUZNEF) [27].
The molecule of 5 is essentially planar with maximum deviations of 0.002(4) Å in C2 and –0.0031(4) Å in C1,
0.001(4) Å in C8 and –0.002(4) Å in C9 for the thiophene rings. The two ring planes of the thiophene groups make a dihedral
angle of 1.6(2)°.
TABLE 1. Crystal Data, Data Collection, and Structure Refinement
Chemical formula
C H BrCl OS
11 5 2 2
CCDC
1447773
Formula weight
Crystal system
Space group
a, Å
368.08
Monoclinic
P2 /n
Radiation (MoK ), Å
α
λ = 0.71073
θ range, deg.
hkl range
3.0-27.6
1
–4, 4; –17, 17; –30, 30
4.0056(2)
13.4966(9)
23.418(2)
94.285(6)
1262.5(1)
4
Reflections
Unique
11886
b, Å
2836
c, Å
R
int
0.038
β, deg.
With I > 2σ(I)
Refinement method
Number of parameters
2134
3
2
V, Å
Full-matrix least-squares on F
Z
154
0.0436
0.1145
1.0
3
2
R(F ) [I > 2σ(I)]
d
x
, g/cm
1.323
2
wR(F ) [I > 2σ(I)]
F(000)
200
–
1
2
μ, mm
0.094
Goodness of fit on F
3
Crystal size, mm
0.07×0.10×0.32
Max / min Δρ, e/Å
0.77 / –0.53
1442

Fig. 1. Molecular structure of 5 showing the atom
numbering scheme. Displacement ellipsoids are drawn at
a 50% probability level. H atoms are shown as spheres of
arbitrary radii.
TABLE 2. Selected geometrical parameters (Å, deg.) for 5
Br1–C11
S1–C1
1.867(4)
1.697(4)
1.703(4)
1.711(4)
90.6(2)
O1–C5
S1–C4
1.215(6)
1.689(4)
1.725(4)
1.707(4)
90.8(2)
S2–C11
S2–C8
Cl1–C1
Cl2–C4
C1–S1–C4
S1–C1–Cl1
Br1–C11–S2
C2–C5–C6–C7
C5–C6–C7–C8
C8–S2–C11
S1–C4–Cl2
Br1–C11–C10
O1–C5–C6–C7
C8–S2–C11–Br1
114.9(2)
119.7(2)
178.(4)
119.7(3)
126.7(3)
–0.8(7)
–179.8(4)
–178.9(3)
The crystal packing does not present geometrical parameters corresponding to the classical hydrogen bonding [28],
and is governed by non-conventional hydrogen bond-type intermolecular interactions. The structure of 5 is built up from the
self-assembly of molecules via the C---H⋯O hydrogenbonding (Fig. 2 and Table 3). The C10---H10⋯O1 interactions
Fig. 2. Partial view of the crystal packing shows the hydrogen bonds formed (C---H⋯O).
1443

TABLE 3. Hydrogen Bond Geometry (Å,deg.)
D---H⋯A
D---H
H⋯A
D⋯A
D---H⋯A
i
C10---H10⋯O1
C7---H7⋯O1
C6---H6·⋯Cl1
C6---H6⋯S2
0.9300
0.9300
0.9300
0.9300
2.49
2.43
2.54
2.84
3.406(5)
2.769(6)
3.257(4)
3.193(4)
167
102
134
104
D – donor; A – acceptor; H – hydrogen.
i
Symmetry codes: 1/2–x, –1/2+y, 1/2–z.
(1/2–x, –1/2+y, 1/2–z) form extended zigzag chains related by 2 screw axes running along the [010] direction. These chains
1
may be described in a graph-set notation as C(8) [ 29, 30 ]. The network is reinforced by weak intermolecular non-
conventional C7---H7⋯O1, C6---H6⋯Cl1, and C6---H6⋯S2 hydrogen bonds. These hydrogen bonds contribute to the
stabilization of the crystal structurewhich packs with an efficiency of 71.4% of the filled space.
CONCLUSIONS
The new thiophene chalcone compound was synthesized by the Claisen-Schmidt condensation method. The
structure was unambiguously assigned by X-ray diffraction studies. The IR, NMR, and HRMS results were consistent with
the structural results. In the crystal structure of (E)-3-(5-bromothiophen-2-yl)-1-(2,5-dichlorothiophen-3-yl)-2-propen-1-one,
the molecules are linked by C---H⋯O hydrogen bonds, forming extended zigzag chains running along the [010] direction.
The crystal packing is completely dominated by cohesive weak interactions among the neighboring molecules producing
an efficient packing with 71.4% of the occupied space.
J. Jamalis wishes to thank the Ministry of Higher Education (MOHE) for funding this research under the Research
University Grant (RUP) with vote No. 07J48 and Fundamental Research Grant Scheme (FRGS) of vote numbers 4F448. This
work was also supported by the Laboratorio de Rayos-X del Parque Tecnológico Guatiguará (PTG), Universidad Industrial
de Santander (UIS), Colombia, and FONACIT (grant LAB-97000821), Venezuela.
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