Synthesis, characterization, and crystal structure of 1-(4-chloro-benzoyl)- 3-naphthalen-1-yl-thiourea

Article abstract of DOI:10.1023/A:1027429814989

1-(4-Chloro-benzoyl)-3-naphthalen-1-yl-thiourea has been synthesized and characterized by elemental analysis, IR spectroscopy, and mass spectrometry. The crystal and molecular structure of the title compound has been determined from single crystal X-ray d

Full text of DOI:10.1023/A:1027429814989

C
Journal of Chemical Crystallography, Vol. 33, No. 12, December 2003 ( 2003)
Synthesis, characterization, and crystal structure of
1-(4-chloro-benzoyl)-3-naphthalen-1-yl-thiourea
Hakan Arslan,(1,2) Ulrich Flo¨rke,(3) and Nevzat Ku¨lcu¨(1)
Received August 19, 2002
1-(4-Chloro-benzoyl)-3-naphthalen-1-yl-thiourea has been synthesized and characterized
by elemental analysis, IR spectroscopy, and mass spectrometry. The crystal and molecular
structure of the title compound has been determined from single crystal X-ray diffraction
˚
˚
data. It crystallizes in the triclinic space group P-1, with a = 6.962(1) A, b = 10.770(3) A,
1
˚
c = 11.738(2) A, = 65.76(2) , = 80.03(1) , = 84.86(2) , and Dcalc = 1.432 g cm
for Z = 2. The thermal behavior of the compound has been studied by DTA and TG. The
antibacterial activities of the title compound were investigated for three Gram (+) and two
Gram ( ) bacteria by employing broth microdilution method and subsequently, inhibitory
activity against yeast-like fungi was also determined.
KEY WORDS: Thioureas; synthesis; X-ray structures; DTA/TG; antibacterial activities.
Introduction
properties, particularly the redox behavior of the
metallic complexes.7–10
The biological activities of the complexes
In previous studies, metal complexes of N,
N-dialkyl-N0-benzoylthiourea derivatives having
such properties were synthesized and their ther-
mal behaviour was examined.11–13 On the basis
of the literature search, we could not find synthe-
sis and characterization of 1-(4-chloro-benzoyl)-
3-naphthalen-1-yl-thiourea (BNT) compound. In
this paper we report the preparation, characteriza-
tion, chemical structural properties, thermal be-
haviors, decomposition kinetics, and microbio-
logical activities of BNT.
with thiourea derivatives have been well doc-
umented and thiourea derivatives have been
successfully screened for various biological
actions.1–4 Thiourea derivatives have been found
to be useful ligands for the potential determina-
tion of traces of the transition metals by means
of normal phase chromatography.5 The complex-
ation capacity of these compounds has been re-
ported in several papers.5,6 These derivative com-
pounds can induce a large alternation of electronic
effects of the ligands and therefore a change of the
Experimental
(1) Department of Chemistry, Faculty of Arts and Sciences, Mersin
University, 33343 Mersin, Turkey.
(2) School of Chemistry and Biochemistry, Georgia Institute of Tech-
nology, Atlanta, Georgia.
Instrumentation
(3) Department of Inorganic and Analytical Chemistry, University of
Paderborn, Paderborn, Germany.
* To whom correspondence should be addressed; e-mail: arslanh@
mersin.edu.tr.
Infrared spectra were recorded in the range
4000–400 cm on a Shimadzu 435 spectropho-
tometer, using KBr pellets. Mass spectra were
1
919
C
1074-1542/03/1200-0919/0 2003 Plenum Publishing Corporation

920
Arslan, Flo¨rke, and Ku¨lcu¨
Table 1. Summary of Crystallographic Data and Parameters of
recorded on a VG Autospec, with the FAB tech-
nique. Elemental analyses were carried out on
a Carlo Erba MOD 1106 instrument. Melting
point determinations were performed with a digi-
tal melting point instrument from Electrothermal
model 9200.
1-(4-Chloro-Benzoyl)-3-Naphthalen-1-yl-Thiourea
Empirical formula
Formula weight
CCDC deposit no.
Temperature
C18H13N2OSCl
340.81
CCDC-189945
203(2) K
˚
Wavelength
0.71073 A
The DTA and TG curves are obtained with
Shimadzu DT-40 model simultaneously with DTA
and TG apparatus. Experimental data: heating
Crystal system
Space group
Unit cell dimensions
Triclinic
P-1
˚
a = 6.962(1) A
˚
˚
b = 10.770(3) A
1
rate, 10 K min ; atmosphere, nitrogen; flow rate
c = 11.738(2) A
1
of furnace atmosphere, 60 mL min ; crucible,
= 65.76(2)
= 80.03(1)
Platinum; sample size, 6 mg; reference substance,
-Al2O3.
= 84.86(2)
3
˚
Volume
790.2(3) A
Single crystal X-ray data were collected on a
Bruker AXS P4 diffractometer using monochro-
mated Mo K radiation. Standard reflections mon-
itored after every 300 reflections showed only ran-
dom deviations. LP corrections were applied. The
structure was solved by direct and conventional
Fourier methods. Full-matrix least-squares refine-
ment were based on F2. Programs used for cal-
culations was SHELXTL14. Further details con-
cerning data collection and refinement are given
in Table 1.
Z
2
Density (calculated)
Absorption coefficient
F(000)
Crystal size
Theta range for data collection 2.07–24.99
1.432 Mg/m3
1
0.379 mm
352
0.50 0.42 0.40 mm3
Index ranges
1
h
8, 11
k
11,
13
3419
l
13
Reflections collected
Independent reflections
Absorption correction
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2 (I)]
R indices (all data)
2695 [Rint = 0.0229]
None
Full-matrix least-squares on F2
2695/0/209
1.065
R1 = 0.0317, wR2 = 0.0782
R1 = 0.0348, wR2 = 0.0803
3
˚
0.233 and 0.256 e.A
Largest diff. peak and hole
Synthesis of the compound
All chemicals used for the preparation of
the compound were of reagent grade quality. The
compound was obtained in acetone using the
method given in the previous study of Arslan
et al.15,16 The 4-chloro-benzoylisothiocyanate
was obtained from 4-chloro-benzoyl chloride
(5 10 2 mol) and KSCN (5 10 2 mol) at 40 C
(30 min). A solution of the naphthalen-1-ylamine
was added to the mixture for 15 min at room
temperature and stirred for 2 h. The solid or-
ganic phase was filtered and recrystallized from
ethanol/dichloromethane (1:1).
341 (M+1, 100), 185 (37), 139 (40), 201 (25), and
111 (35).
Antimicrobiological activity studies
Antibacterial activities of the compound
were tested against Gram (+) and Gram ( )
bacteria such as Escherichia coli (ATCC 25922),
Pseudomonas aeruginosa (ATCC 27853),
Enterococcus faecalis (ATCC 29212), Staphyloc-
ccus aureus (ATCC 25923), and Staphylocccus
epidermidis (ATCC 12228), and the antifungal
activities of compounds against some yeast like
fungi such as Candida albicans (ATCC 90028),
Candida krusei (ATCC 6258), Candida glabrata
(ATCC 32554), and Candida parapsilosis (ATCC
22019). Minimal inhibitory concentrations
1-(4-Chloro-benzoyl)-3-naphthalen-1-yl-
thiourea (BNT). Color: white. Yield: 87%, m.p.
183–185 C. Anal. required for C18H13N2OSCl:
C, 63.4; H, 3.8; N, 8.2. Found: C, 63.5; H, 3.9;
1
---
N, 8.3%. IR (KBr pellet, cm ): (N H) 3186
---
(s, br), (C O) 1670 (s). MS(FAB), m/z (%) =
---

Synthesis and characterization of BNT
921
(MICs) were determined by broth microdilution
method following the procedures recommended
by the National Committee for Clinical Labora-
tory Standards.17,18 Amikacin and Flucanozole
were used as reference compounds for bacteria
and fungi, respectively.
Mueller-Hinton broth (Difco Laboratories,
Detroit, MI) was used when testing bacterial
strains. For Candida species, Saboraud Dextroz
broth (Difco) was used. The inoculum density
was 1 106 cfu/mL for bacteria and fungi. The
compounds under investigation were dissolved in
100% dimethysulfoxide. The solutions in the test
medium were furnished the required concentra-
tion ranging from 1024 to 0.5 g/mL. The mi-
crotiter plates were incubated at 35 C and read vi-
sually after 24 h. For Candida species, incubation
period was 48 h. The MIC values were recorded
as the lowest concentrations of the substances that
had no visible turbidity.
troscopy, mass spectrometry, and single crys-
tal X-ray diffraction methods) of 1-(4-chloro-
benzoyl)-3-naphthalen-1-yl-thiourea. All of the
characterization data are in agreement with the
molecular structure of 1-(4-chloro-benzoyl)-3-
naphthalen-1-yl-thiourea. The IR region between
2900and3300cm 1 showsagroupofpeakscorre-
---
sponding to the aromatic C H absorption bands
---
and the N H stretching vibration is observed in
the region around 3186 cm 1 as a broad band.
1-(4-Chloro-benzoyl)-3-naphthalen-1-yl-
thiourea melts at 458 K with simultaneous
decomposition. The first mass loss is observed
at 458 K in the TG profile. The DTA/TG/DTG
profiles of BNT are shown in Fig. 1. From the TG
curve, it appeared that the sample decomposes in
two stages over the temperature range 298–675 K.
The first decomposition occurs between 298 and
513 K with a mass loss of 69.1% and the second
decomposition starts at 513 K and ends at 675 K
with a 30.9% mass loss. From the corresponding
DTA profile, three endothermic peaks are noted,
the first between 458 and 467 K with a maximum
at 458 K, second between 467 and 515 K with
a maximum at 493 K, and the third between
Results and discussion
We herein report the synthesis and full
characterization (by elemental analysis, IR spec-
Fig. 1. DTA/TG/DTG diagram of 1-(4-chloro-benzoyl)-3-naphthalen-1-yl-thiourea.

922
Arslan, Flo¨rke, and Ku¨lcu¨
Table 2. Kinetic Data of 1-(4-Chloro-Benzoyl)-3-Naphthalen-1-yl-
˚
Table 3. Selected Bond Lengths (A) and Angles ( ) of BNT
Thiourea
Bond lengths
---
C(1) N(1)
Coats–Redfern Horowitz–Metzger
---
C(2) O(1)
1.3974(19)
1.6696(17)
1.327(2)
1.224(2)
1.488(2)
1.4408(19)
1.7372(16)
Stage
I
Parametersa
method
method
---
---
C(1) S(1)
---
C(2) C(3)
---
N(2) C(9)
C(1) N(2)
E
A
1S
r
155.4
3.3 1014
28.8
158.8
5.7 1014
33.2
---
---
N(1) C(2)
1.377(2)
C(6) Cl
Bond Angles
---
---
---
---
N(2) C(1) N(1) 116.72(14) C(1) N(1) C(2) 128.11(13)
0.9991
0.9993
--- --- --- ---
N(2) C(1) S(1) 124.47(12) N(1) C(2) O(1) 122.77(14)
--- --- --- ---
II
E
A
1S
r
101.5
1.5 107
86.1
100.9
1.5 107
112.6
C(9) N(2) C(1) 123.59(13) N(1) C(2) C(3) 115.88(13)
---
---
---
---
C(2) C(3) C(4) 121.68(14) N(2) C(9) C(10) 118.36(14)
0.9525
0.9416
1
aUnit of parameters: E in kJ mole 1, A in s 1, 1S in J mole
1, r: correlation coefficient of the linear plot.
K
bond lengths and angles in the naphthalene,
substituted benzene, and the thiourea moiety
---
are as expected, i.e. C(1) S(1) bond length of
515 and 676 K with a maximum at 567 K. The
end product of the first stage is chloro-benzene
˚
˚
---
1.6696(17) A and C(2) O(1) of 1.224(2) A,
both typical double bonds for thiourea deriva-
radical (
) and this is confirmed by results of
---
tives. The C N bond lengths are all shorter than
normal C N single bond lengths of 1.479 A ,
TG and mass spectrum data (111 m/z). In the
second stage, chloro-benzene radical undergoes
pyrolysis.
16
˚
---
Coats–Redfern19 and Horowitz–Metzger20
methods were used to evaluate the decomposi-
tion kinetics. From the TG curves, activation en-
ergy E , entropies 1S , and preexponential factor
A, of the thermal decomposition have been eluci-
dated. The decomposition kinetic parameters are
presented in Table 2.
The molecular structure of 1-(4-chloro-
benzoyl)-3-naphthalen-1-yl-thiourea, showing
the atom numbering scheme and selected bond
lengths and angles are given in Fig. 2 and Table 3,
respectively. Table 4 lists the nonhydrogen
atomic coordinates. In the molecule the overall
Table 4. Atomic Coordinates (104) and Equivalent Isotropic Dis-
3
2
˚
placement Parameters (10 A ) for BNT
x/a
y/b
z/c
Ueaq
Cl(1)
S(1)
O(1)
N(1)
N(2)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
14556(1)
3018(1)
5872(2)
5626(2)
3132(2)
3918(2)
6550(2)
8473(2)
9792(2)
11662(2)
12183(2)
10882(2)
9028(2)
1324(2)
311(2)
3295(1)
226(1)
3678(1)
1435(1)
844(1)
127(1)
986(1)
51(1)
35(1)
34(1)
27(1)
28(1)
27(1)
26(1)
25(1)
29(1)
32(1)
32(1)
33(1)
30(1)
27(1)
32(1)
37(1)
36(1)
28(1)
36(1)
39(1)
37(1)
30(1)
26(1)
4337(1)
2030(1)
2848(1)
1793(2)
3247(2)
3160(2)
2094(2)
2126(2)
3226(2)
4281(2)
4256(2)
2790(2)
3357(2)
3371(2)
2802(2)
2213(2)
1614(2)
1074(2)
1113(2)
1653(2)
2215(2)
750(1)
841(1)
1591(1)
1120(2)
1769(2)
2895(2)
3399(2)
2736(2)
1815(2)
1288(2)
2057(2)
3341(2)
3917(2)
5244(2)
5785(2)
5016(2)
3732(2)
3142(2)
2099(2)
2201(2)
528(2)
616(3)
1008(3)
2813(3)
2967(2)
1287(2)
Fig. 2. Molecular structure of BNT in the crystal showing
the atom numbering scheme. Thermal ellipsoids are shown
at the 50% probability level.
aUeq is defined as one third of the trace of the orthogonalized Ui j
tensor.

Synthesis and characterization of BNT
923
Fig. 3. Crystal packing diagram viewed along [100].
Antibacterial activities of the compound
were tested against Gram (+) and Gram ( ) bac-
teria. The results obtained from the antibacte-
rial and antifungal efficacy studies were found
as: bacteria/fungi (MIC value ( g/mL)/reference
MIC value ( g/mL)): Escherichia coli (256/1),
Pseudomonas aeruginosa (128/2), Enterococcus
faecalis (128/32), Staphylocccus aureus (128/4),
Staphylocccus epidermidis (128/4), Candida al-
bicans (256/0.5), Candida krusei (256/32), Can-
dida glabrata (512/4), and Candida parapsilosis
(256/2). It was determined that the benzoylth-
iourea derivative under investigation inhibit the
growth of some Gram (+) and Gram ( ) bacte-
ria and fungi at different levels but the antibacte-
rial efficacy is better than antifungal activity. The
highestMICvalue(512 g/mL)wasfoundagainst
the growth of Candida glabrata.
˚
---
˚
---
being C(2) N(1)=1.377(2) A, C(1) N(1) =
˚
---
1.3974(19) A and C(1) N(2) = 1.327(2) A. All
the other bond lengths fall within the expected
---
---
---
---
---
range. The unit H N(2) C(1) N(1) C(2)
O(1) forms an intramolecular hydrogen bond
---
N(2) H O(1) of 1.996 A (N H 0.87 A) to
give a six-membered ring; the N(2) H O(1)
angle is 133.4 . The conformation of the molecule
with respect to the thiocarbonyl and carbonyl
moieties is definitely twisted as reflected by
the torsional angles O(1) C(2) N(1) C(1)
and C(2) N(1) C(1) N(2) of 4.8(3) and
4.2(2) , respectively.
˚
˚
---
--- ---
---
---
---
---
---
---
The crystal packing shows intermolecular
hydrogen bonding patterns N(1) H(1A) S(1)
---
˚
---
( x + 1, y, z) with H S 2.420 A, N H
S
---
151.8 ; N(2) H(2A) O(1) ( x + 1, y + 1,
˚
---
z) with H O 2.244 A, N H O 139.7 ; and
---
C(11) H(11A) O(1) ( x, y + 1, z) with
˚
---
O 2.489 A, C H O 155.9 . These val-
H
Acknowledgments
˚
---
---
ues are normalized for N H 1.030 A and C H
˚
1.080A. Figure3depictsthecrystalpackingalong
This work was supported by Mersin Univer-
[100].
sity Research Fund (Project No. FEF.K.HA.99.1).

924
Arslan, Flo¨rke, and Ku¨lcu¨
8. Shen, X.; Shi, X.; Kang, B.; Tong, Y.; Liu, Y.; Gu, L.; Liu, Q.;
Huang, Y. Polyhedron 1998, 18, 33.
9. Mohamadou, A.; Dechamps-Olivier, I.; Barbier, J.P. Polyhe-
dron 1994, 13, 3277.
We thank Dr. N. Duran for the interpretation of an-
timicrobiological activity.
10. Dechamps-Olivier, I.; Guillion, E.; Mohamadou, A.; Barbier,
J.P. Polyhedron 1996, 15, 3617.
11. Ozpozan, N.; Ozpozan, T.; Arslan, H.; Karipcin, F.; Ku¨lcu¨, N.
Supplementary material CCDC-189945 contains the supplemen-
tary crystallographic data for this paper. These data can be obtained
free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from
the Cambridge Crystallographic Data Centre (CCDC), 12 Union
Road, Cambridge CB2 1EZ, UK; fax: +44(0)1223-336033; email:
deposit@ccdc.cam.ac.uk].
¨
¨
Thermochim. Acta 1999, 336, 97.
12. Ozpozan, N.; Arslan, H.; Ozpozan, T.; Ozdes¸, N.; Ku¨lcu¨, N.
¨
¨
¨
Thermochim. Acta 2000, 343, 127.
¨
¨
13. Ozpozan, N.; Arslan, H.; Ozpozan, T.; Merdivan, M.; Ku¨lcu¨, N.
J. Ther. Anal. 2000, 61, 955.
14. Sheldrick, G.M. SHELXTL, Structure Determination Software
Program, Version 5.10; Bruker Analytical X-ray Systems, Inc.:
Madison, WI, 1998.
15. Arslan, H.; Flo¨rke, U.; Ku¨lcu¨, N. Transit. Metal Chem. 2003,
28, 816.
References
16. Arslan, H.; Flo¨rke, U.; Ku¨lcu¨, N. Acta Crystallogr. Sect. E,
2003, E59, o641.
17. National Committee for Clinical Laboratory Standards. Meth-
ods for Dilution Antimicrobial Susceptibility Tests for Bac-
teria That Grow Aerobically. Approved Standard, M7-A4;
Viallanova, PA, 1997.
18. National Committee for Clinical Laboratory Standards. Refer-
ence Methods for Broth Dilution Antifungal Susceptibility Test-
ing Yeasts. Approved Standard, M27-A; Viallanova, PA, 1997.
19. Coats, A.W.; Redfern, J. P. Nature 1964, 201, 68.
20. Horowitz, H.H.; Metzger, G. Anal. Chem. 1963, 35, 1464.
1. Frech, F.A.; Blanz, E.J. Cancer Res. 1965, 25, 1454.
2. Blanz, E.J.; French, F.A. Cancer Res. 1965, 28, 2419.
3. Frech, F.A.; Blanz, E.J. J. Med. Chem. 1966, 9, 585.
4. Frech, F.A.; Blanz, E.J.; Amaral, J.R.D.; French, D.A. J. Med.
Chem. 1970, 13, 1117.
5. Ko¨nig, K.H.; Schuster, M.; Schneeweis, G.; Steinbrech, B. Zeit.
Anal. Chem. 1984, 319, 66.
6. Schuster, M.; Kugler, B.; Ko¨nig, K.H. J. Anal. Chem. 1990,
338, 717.
7. Guttmann, M.; Lubert, K.H.; Beyer, L. Fresenius J. Anal. Chem.
1996, 356, 263.