Synthesis, crystal structure and spectroscopic characterization of {6-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-2-oxo-1,3-benzothiazol-3(2H)-yl}acetic acid

Article abstract of DOI:10.1007/s10870-010-9744-4

The title compound {6-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-2-oxo-1,3- benzothiazol-3(2H)-yl}acetic acid was prepared and characterized by elemental analyses, FT-IR, ¹H NMR spectroscopy, X-ray diffraction. A quantum-chemical calculation was performed using the CNDO method. In the title compound, C₁₈H₁₁ClN₂O₃S₂, the crystal structure is stabilized by intermolecular hydrogen bonds (C-H???O=C) to form centrosymmetric R-{2}^{2} (16) dimers and the C-H???O, O-H???N, and C-H???N interactions generating the graph set motifs R-{2}^{2} (9) and R-{2}^{2} (22). Index Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-010-9744-4

J Chem Crystallogr (2010) 40:816–820
DOI 10.1007/s10870-010-9744-4
ORIGINAL PAPER
Synthesis, Crystal Structure and Spectroscopic Characterization
of {6-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-2-oxo-1,3-benzothiazol-
3(2H)-yl}acetic acid
•
•
Abdullah Aydın Mehmet Akkurt
¨
•
•
Leyla Uzun Leyla Yıldırım Tijen Onkol
Received: 12 November 2009 / Accepted: 12 February 2010 / Published online: 25 February 2010
Ó Springer Science+Business Media, LLC 2010
Abstract The title compound {6-[2-(2-chlorophenyl)-1,
3-thiazol-4-yl]-2-oxo-1,3-benzothiazol-3(2H)-yl}acetic acid
was prepared and characterized by elemental analyses, FT-
Small and simple heterocyclic molecules such as
benzothiazole and its derivatives represent the types of
compounds of versatility for their utilization. They contain
extended p-delocalized systems which are capable of
binding to DNA molecules via p–p interactions and there-
fore exhibit complex biological properties, as antitumor,
anti-infective, antifungal or antihelmintic activities [3].
This title compound, C18H11ClN2O3S2, was synthesized
to serve as an inhibitor for the cyclooxygenase (COX)
enzyme. However, certain inhibitor activity was seen
neither on COX-1 nor on COX-2 [4]. The COX enzyme
has two forms: COX-1 and COX-2. The measure of COX-
1 and COX-2 inhibitions of the active compounds was
also investigated by using in vitro human whole blood
assay [4].
1
IR, H NMR spectroscopy, X-ray diffraction. A quantum-
chemical calculation was performed using the CNDO
method. In the title compound, C18H11ClN2O3S2, the crystal
structure is stabilized by intermolecular hydrogen bonds
(C–HÁÁÁO=C) to form centrosymmetric R22(16) dimers and the
C–HÁÁÁO, O–HÁÁÁN, and C–HÁÁÁN interactions generating the
graph set motifs R22(9) and R22(22).
Keywords Crystal structure Á Acetic acid Á X-ray Á
CNDO method
Introduction
2-Benzothiazolinone (2-benzoxazolinone) derivatives
exhibit a variety of pharmacological effects, including
analgesic and anti-inflammatory activity [1, 2].
Results and Discussion
Chemistry
The 1,3-benzothiazol-2(3H)-one was prepared via con-
densation of 2-aminothiophenol with the urea under
microwave irradiation (MWI). The 1,3-benzothiazol-
2(3H)-one was converted to 6-(2-bromoacetyl)-2-oxo-1,
3-benzothiazole by bromoacetic acid exchange reaction
followed under MWI. After, to synthesize 6-[(2-chloro-
phenyl)-1,3-thiazol-4-yl]-2-oxo-1,3-benzothiazole, the 6-
(2-bromoacetyl)-2-oxo-1,3-benzothiazole was condensed
with 2-chlorothiobenzamide in diglyme. Acetic acid deriva-
tive was synthesized by the acid hydrolysis of the corre-
sponding ethyl ester which was prepared by the reaction of
6-[(2-chlorophenyl)-1,3-thiazol-4-yl]-2-oxo-1,3-benzothia-
zole with ethyl bromoacetate in the presence of metallic
sodium [4] (Scheme 1).
A. Aydın (&)
Department of Science Education, Faculty of Education,
Kastamonu University, 37200 Kastamonu, Turkey
e-mail: aaydin@kastamonu.edu.tr
M. Akkurt
Department of Physics, Faculty of Arts and Sciences,
Erciyes University, 38039 Kayseri, Turkey
¨
L. Uzun Á T. Onkol
Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
Gazi University, 06330 Ankara, Turkey
L. Yıldırım
Department of Physics Engineering, Faculty of Engineering,
Hacettepe University, 06532 Ankara, Turkey
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J Chem Crystallogr (2010) 40:816–820
817
Scheme 1 Synthetic route of
title compound
H
N
H
N
NH
SH
2
c
a,b
O
O
S
S
Br
S
N
O
Cl
COOH
N
S
d,e
O
S
N
Cl
a: Urea, MWI; b: PPA, BrCH2COOH, MWI; c: 2-Chlorothiobenzamide, diglyme;
d: NaOEt, BrCH2COOC2H5; e: HCI
Crystal Structure Analysis
1.2Ueq(C). The isotropic displacement parameter of the
H15 atom bounded to the C15 atom was fixed at the value
2
of 0.5 A during the refinement procedure. The 24 dis-
˚
In this study, the crystal structure of the title com-
pound, {6-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-2-oxo-1,
3-benzothiazol-3(2H)-yl}acetic acid, was determined by
X-ray analysis. The data were collected on an Enraf–No-
nius Turbo CAD-4 [5] diffractometer with a scintillation
detector. Diffraction measurements were made at 293 K.
The cell was refined on a CAD-4 Express and the data were
reducted on a XCAD-4 [6]. The structure was solved by
direct methods using SIR-97 [7] and refined by a full-
matrix least-squares procedure using the program SHEL-
XL-97 [8]. The H atoms were positioned geometrically and
refined by riding rigid body approximation, with C–H
agreeable reflections were omitted in the refinement. The
software used to prepare material for publication: WinGX
publication routines [9]. Empirical absorption corrections
were applied by the w-scan method [10].
An ORTEP drawing [11] of the title molecule with 30%
probability displacement thermal ellipsoids and atom-
labeling scheme are shown in Fig. 1. The crystal data and
structure refinement details for the compound are given in
Table 1. The selected bond lengths and angles are given in
Table 2.
The bond lengths and angles are in the normal range
[12–14]. The benzothiazole ring is essentially planar
˚
distances in the range 0.93 A and with Uiso(H) =
Fig. 1 An ORTEP view of the
title compound with the atom
numbering scheme.
Displacement ellipsoids for
non-H atoms are drawn at the
30% probability level
123

818
J Chem Crystallogr (2010) 40:816–820
˚
Table 1 Crystal data and details for structure determination of
C18H11ClN2O3S2
Table 2 Selected bond lengths (A) and angles (°) for C18H11
ClN2O3S2
˚
Bond lengths (A)
CCDC No
731834
C18H11ClN2O3S2
Bond angles (8)
Empirical formula
Formula weight
Temperature (K)
Cl1–C1
S1–C8
1.7333 (18)
1.704 (2)
1.213 (2)
1.375 (2)
1.376 (3)
1.374 (3)
1.383 (3)
1.379 (2)
1.398 (2)
1.474 (2)
1.356 (2)
1.478 (2)
1.398 (2)
1.385 (2)
1.382 (2)
1.398 (2)
1.377 (2)
1.515 (2)
C8–S1–C7
89.72 (9)
402.88
C7–N1–C9
C16–N2–C17
C2–C1–C6
C2–C1–Cl1
C5–C6–C1
N1–C7–C6
N1–C7–S1
112.05 (14)
119.58 (14)
122.13 (17)
116.43 (14)
116.58 (15)
121.99 (15)
113.20 (12)
124.58 (12)
121.04 (14)
112.45 (14)
111.15 (12)
125.48 (18)
124.83 (16)
109.69 (12)
111.59 (14)
125.02 (15)
124.05 (15)
293
O1–C16
N1–C9
˚
Wavelength (A)
0.71073 (MoKa)
Monoclinic
P21/c
Crystal system
Space group
C1–C2
C2–C3
Unit cell dimensions
C3–C4
˚
a (A)
11.9392(16)
13.693(2)
10.468(6)
90
C4–C5
˚
b (A)
C5–C6
C6–C7–S1
˚
c (A)
C6–C7
N1–C9–C10
N2–C13–C14
C13–C14–S2
O1–C16–N2
O1–C16–S2
N2–C16–S2
N2–C17–C18
O2–C18–O3
O2–C18–C17
a (°)
b (°)
c (°)
C8–C9
91.22(3)
90
C9–C10
C10–C11
C11–C12
C12–C13
C13–C14
C14–C15
C17–C18
3
˚
Volume (A )
1711.0(10)
4
Z
Color
Dcalc (g cm-3
Absorption coefficient (mm-1
Light yellow
1.564
)
)
0.489
F(000)
824
Crystal size (mm)
0.40 9 0.40 9 0.40
2.45–26.30
7152
h range for data collection (°)
Collected reflections
Independent reflections
˚
Table 3 Hydrogen-bond parameters (A, °)
˚
˚
˚
D–HÁÁÁA
D–H (A) HÁÁÁA (A) DÁÁÁA (A) D–HÁÁÁA (°)
3440
Number of data with I [ 2r(I)
Absorption correction
2805
O3–H3ÁÁÁN1i
C2–H2ÁÁÁO1ii
C5–H5ÁÁÁN1
C11–H11ÁÁÁO2i
0.82
0.93
0.93
0.93
1.94
2.58
2.53
2.53
2.39
2.713 (2)
3.435 (3)
2.851 (3)
3.291 (3)
3.187 (3)
158
153
101
140
143
w-scan
Tmin
0.828
Tmax
0.828
Rint
0.0184
C15–H15ÁÁÁO2iii 0.93
h
-14 ? 14
-17 ? 17
0 ? 13
Symmetry codes: (i) 1-x, 2-y, -z; (ii) -1 ? x, y, 1 ? z; (iii) 1;
(iv) x, 1/2-y, -1/2 ? z
k
l
Refinement method
Full-matrix
least-squares on F2
In the crystal structure, molecules of the title compound
are linked by intermolecular hydrogen bonds (C–HÁÁÁO=C)
to form centrosymmetric R22(16) dimers. In addition, the
C–HÁÁÁO, O–HÁÁÁN, and C–HÁÁÁN interactions generate rings
of graph set motifs R22(9) and R22(22) [16, 17], forming a
three-dimensional network (Table 3).
Final R indices [I [ 2r(I)]
wR(F2)
Goodnes-of-fit on F2
Structure determination
(D/r)max
0.0330
0.0919
1.010
SIR-97
\0.001
0.47
-3
˚
Dqmax (e A
)
-3
)
˚
Dqmin (e A
-0.33
Theoretical Study
w = 1/[r2(F02) ? (0.049P)2 ? 0.6298P] where P = (F02 ? 2F2c)/3
We have carried out CNDO (Complete Neglect of Differ-
ential Overlap) [18] quantum mechanical calculations on
the title compound. The calculated charge distribution on
the molecule of (I) in the gas phase is as at atoms Cl1, S1,
S2, N1, N2, O1, O2, and O3 are—0.181,-0.065, -0.172,
-0.225, -0.044, -0.408, -0.280, and -0.315e-, respec-
tively. The calculated dipole moment of the title molecule
is ca 7.798 Debye. The highest occupied and lowest
(v2 \ 5) [15]. The plane of the benzothiazole ring (S2/N2/
C10–C16) makes the dihedral angles of 16.92(6) and
4.20(7)° with the S1/N1/C7–C9 and C1–C6 rings, while the
mean planes of these rings form 20.61(8)° with each other.
The torsion angles N2–C17–C18–O2 and N2–C17–C18–
O3 are -0.5(2) and 179.54(14)°, respectively.
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J Chem Crystallogr (2010) 40:816–820
819
Table 4 The important IR and 1H-NMR spectral data of the title
compound
unoccupied molecular orbital energy levels are -9.7805
and 1.1783 eV, respectively. When the values of the geo-
metric parameters of the title molecule are considered,
theoretical calculation results are consistent with experi-
mental results within the error limits.
IR (KBr pelleti) (cm-1
)
1H-NMR (400 MHz,
DMSO-d6) (d)
3200–2100 (–OH stretching, carboxylic 8.39 (d, 1H, H7)
acid, broad)
3062 (C–H stretching, aromatic, weak) 8.38–8.34 (m, 1H, phenyl-
H3)
Experimental
2921 (C–H stretching, alifatic, weak)
8.29 (s, 1H, thiazole-H4)
The FT-IR spectra (KBr pellet, 4000–400 cm-1) of the
compounds were recorded on a Bruker Vector 22 IR (Opus
Spectroscopic Software Version 2.0) spectrometer as KBr
discs. Elemental analysis was performed on Leco 932 C, H,
N, S instrument (St. Joseph, MI, USA) and the data were
within 0.4% of the theoretical values. The 1H-NMRspectra
were recorded with a Varian Mercury-400 FT-NMR spec-
trometer (Varian Inc., Palo Alto, CA, USA), in DMSO-d6.
Melting points of the compounds were recorded on an
Electrothermal-9200 digital melting points apparatus and
were uncorrected.
1726 (C=O, carbonyl, alifatic carboxylic 8.04 (dd, 1H, H5)
acid, strong)
1602 (C=C, carbonyl, aromatic, weak) 7.68–7.64 (m, 1H, phenyl-
H6)
1677 (C=O, carbonyl, lactam, strong)
7.56–7.50 (m, 2H, phenyl-
H4,5
)
766 (1,2-disubstituted benzene,
moderately strong)
7.43 (d, 1H, H4)
4.77 (s, 2H, N–CH2–CO)
Centre and allocated the deposition number CCDC 731834.
Data Acquisition—the Cambridge Crystallographic Data
Centre deposit@ccdc.cam.ac.uk, http://www.ccdc.cam.ac.uk/
deposit. Telephone: (44) 01223 762910, Facsimile: (44)
01223 336033, Postal Address: CCDC, 12 Union Road,
CAMBRIDGE CB2 1EZ, UK.
Synthesis of {6-[2-(2-chlorophenyl)-1,3-thiazol-4-yl]-
2-oxo-1,3-benzothiazol-3(2H)-yl}acetic acid,
C18H11ClN2O3S2
0.002 mol ethyl {6-[(2-chlorophenyl)-1,3-thiazol-4-yl]-2-
oxo-1,3-benzothiazol-3-yl}acetate derivative was refluxed
in hydrochloric acid for 4 h. The reaction mixture was
cooled, and the precipitate was collected by filtration,
washed with water, dried, and crystallized from acetic
acid–water (4:1). Light yellow crystals of {6-[2-(2-chloro-
phenyl)-1,3-thiazol-4-yl]-2-oxo-1,3-benzothiazol-3-yl}ace-
tic acid suitable for X-ray measurements were formed by
slow evaporation. The yield and m.p. are 0.21 g, 5.2%,
222–227 °C, respectively. Elemental analysis: C18H11ClN2
O3S2, calculated (%)/found (%): C: 53.66/53.88, H: 2.75/
2.54, N: 6.95/7.08.
Acknowledgments The authors wish to acknowledge the purchase
of CAD4 diffractometer under grant DPT/TBAG1 of The Scientific
and Technical Research Council of Turkey. In addition, this study is
partly supported by a grant from Gazi University Research Fund
(Project No: 02/2007-20).
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