Synthesis of two novel aroyl thioureas and their use as anion binding receptors

Article abstract of DOI:10.14233/ajchem.2013.13396

New aroyl thioureas; N-nicotinoyl-N'-(4-nitrophenyl) thiourea (3a) and N-nicotinoyl-N'-(2-nitrophenyl) thiourea (3b) were synthesized and studied as anion-binding receptors. Upon adding tetrabutyl ammonium halides (fluoride, chloride bromide and iodide),

Full text of DOI:10.14233/ajchem.2013.13396

Asian Journal of Chemistry; Vol. 25, No. 5 (2013), 2455-2458
http://dx.doi.org/10.14233/ajchem.2013.13396
Synthesis of Two Novel Aroyl Thioureas and Their Use as Anion Binding Receptors
1,*
2
1
FATMA AYDIN , NAZAN TUNOGLU and DOGAN AYKAC
1Department of Chemistry, Canakkale Onsekiz Mart University, 17100 Canakkale, Turkey
2Department of Chemistry, Hacettepe University, 06532 Beytepe, Ankara, Turkey
*Corresponding author: E-mail: faydin@comu.edu.tr
(Received: 6 January 2012;
Accepted: 9 November 2012)
AJC-12380
New aroyl thioureas; N-nicotinoyl-N'-(4-nitrophenyl) thiourea (3a) and N-nicotinoyl-N'-(2-nitrophenyl) thiourea (3b) were synthesized
and studied as anion-binding receptors. Upon adding tetrabutyl ammonium halides (fluoride, chloride bromide and iodide), cyanide and
hydroxide ions to their solutions in DMSO respectively, the colour of the solutions has shown striking changes from pale yellow to
brillant yellow or red. The binding effects of the anions were investigated by UV-VIS spectroscopic method and 1H NMR titrations.
Key Words: N-Substituted thiourea, Anion coordination, UV-VIS and 1H NMR titrations.
of proteins7 and they have been widely used in developing
anion receptors and sensors.
INTRODUCTION
Over the past few years, the recognition and sensing
of various biologically and/or environmentally important
anions such as F-,AcO-, H2PO4-, CN- OH-, etc. have been a key
Herein, we report two new aroyl thiourea receptors 3(a,
b), given in Scheme-I, which are avid binders of cyanide,
hydroxide ions and fluoride anion among halide anions such
research area of anion coordination known as anion binding
as chloride, bromide, iodide, as tetrabutylammonium salts.
Structurally, compounds 3a and 3b are newly introduced
chemistry1-8. In this context, the coordination chemistry of
anions is a relatively new area of research as opposed to that
receptor nicotinoylthioureas that are substituted with NH groups
of o- and p-nitrophenylamines in their extended framework.
of cations9. Anion binding chemistry using neutral host
molecules has been extensively studied as a result, anions play
EXPERIMENTAL
in various industrial processes, environmental sciences and
enzymatic activity in organisms, clinical treatment of various
disease states, etc.10.
The 1H and 13C NMR spectra were recorded on a resolution
Fourier transform Bruker NMR spectrometer operating at 400
and 101.6 MHz. Infrared absorption spectra were obtained
from a Perkin Elmer BX II spectrometer in KBr discs and
were reported in cm-1 units. The UV-VIS spectra were measured
using Perkin-Elmer WinLab series spectrometer. MS spectra
were recorded on anAgilent 5973 inert mass selective detector
equipped with direct insertion probe. Melting points were
measured on an electrothermal IA 9100 apparatus using a
capillary tube. All reagents were purchased from Merck
Chemical Co.
Among the many inorganic anions, fluoride is drawing a
special attention due to its beneficial (e.g. prevention of dental
caries and treatment of osteoporosis) as well as detrimental
(e.g. fluorosis) roles11. Cyanide ion is a species of high toxicity
found mostly in industrial effluents. Inorganic cyanide salts
are often used in metallurgical industry activities such as metal
surface treatment, but also in mining industry (e.g. for gold
extraction)12. Iodide is mainly associated with biological
activities such as thyroid function and neurological activity13.
The anion binding mainly occurs through weak hydrogen
bonding or electrostatic interactions, thus, is usually weaker
than cation binding. Anion binding sites of receptors may
contain neutral H-bond donor groups such as (thio)ureas14,
calix[4]pyrroles, porphyrins or, activated amides as well as
positively charged guanidinium or ammonium groups which
bind anions based on electrostatic interactions. In particular,
amide NH groups are well-known to be involved in anion binding
General synthesis of the aroyl thioureas (3a, b):A mixture
of nicotinyl chloride hydrochloride (1.769 g, 10 mmol), KSCN
(0.969 g, 10 mmol) and 20 mL of acetonitrile was refluxed
with stirring for 1 h, then, a solution of 10 mmol of 2- or 4-
nitroaniline in 20 mL acetonitrile was added dropwise to the
nicotinoyl isothiocyanate hydrochloride for 0.5 h period at
ambient temperature. When the solution was added completely,
the resulting mixture was then refuxed for 4 h and the progress

2456 Aydin et al.
Asian J. Chem.
O
O
S
O
S
Ar'
C
KSCN
Ar'-NH2
N
H
N
H
Cl
N
acetonitrile
N
N
N
3 (a-b)
1
2 (a-b)
NO2
S
O
S
O
NH2
NH2
NO2
Ar'-NH2 :
N
H
N
H
N
H
N
H
NO2
O2N
N
N
2a
2b
3a
Scheme-I: Synthesis of N-nicotinoyl-N'-(4-nitrophenyl)thiourea (3a) and N-nicotinoyl-N'-(2-nitrophenyl)thiourea (3b)
3b
of reaction was controlled by TLC. After cooling, the solution
was poured into a beaker containing ice-water mixture. The
yellowish precipitate was altered off and washed with distilled
water several times and then dried under vacuum. Recrystalli-
zation from acetone yielded 84 % and 87 % of the pure yellow
products, respectively.
and 1347 cm-1 were assigned to the -N-C=S vibrations.Vibration
bands at 845 and 860 cm-1 are known as the relatively high
frequency values of the ν(C=S), indicated a strong double bond
character of this group in aroylthioureas. Two singlet signals
at 12.61 and 11.95 ppm for 3a; 12.65 and 12.17 ppm for 3b in
1H NMR spectrum ascribed to NH protons. Multiplet signals
in the range 7.47-8.99 ppm were assigned to nicotinoyl and
nitrophenyl aromatic ring protons. Bands at 179.5, 180.4 for
C=S and 171.3, 170.2 for C=O ascribed carbon atoms with their
13C NMR spectra for 3a and 3b, respectively. In addition, mass
spectra of thiourea derivatives (3a and 3b) were obtained to
observe [M]+ ions at 302.
Anion binding interaction studies: Upon addition of OH–,
CN–, F–, Cl–, Br– and I– (as their tetrabutylammonium salts) in
DMSO solutions, the bindings of these anions to host (3a, b)
were investigated by monitoring the changes in the UV-VIS
spectra and the colour changes were also observed by 'naked-
eye' (Figs. 1-4). The spherical halides were investigated first.
However, the additions of either I–, Br– or Cl– afforded
only minor changes in the UV-VIS absorbance spectra and
we concluded that very weak, binding of these anions occurred,
if any. In the case of F- and CN-, the addition of the anions into
DMSO solutions of 3a afforded major changes in the UV-VIS
absorbance values (Figs. 1). However there was no significant
change with 3b (Fig. 2).
N-Nicotinoyl-N'-(4-nitrophenyl) thiourea (3a), C13H10N4O3S,
was obtained as bright yellow crystals (87 %); m.p. 212-213
ºC; IR (KBr, νmax, cm-1 pellet): 3005 (N-H), 1673 (C=O), 1518
1
(C(O)-N), 1283 (N-C(S), thioureido), 845 (C=S); H NMR
(DMSO-d6): δ = 12.61 (s, 1H, N-H), 11.95 (s, 1H, N-H), 8.992-
7.47 (8H,Ar-H); 13C NMR (CDCl3) δ ppm: 179.5 (C=S); 170.2
(C=O); 146.1; 137.1; 134.7; 132.9; 131.8; 130.1; 130.0; 129.6;
128.2(Ar); MS: 302, 180, 138.
N-Nicotinoyl-N'-(2-nitrophenyl)thiourea (3b):
C13H10N4O3S, was obtained as dark yellow crystals (84 %);
m.p. 206-207 ºC; IR (KBr, νmax, cm-1 pellet) : 3334.8 (N-H),
1674 (C=O), 1511 (carbonyl C-N), 1346 (N-C=S, thioureido),
1
860 (C=S); H NMR (DMSO-d6), δ ppm: 12.65 (s, 1H,
C=ONHC(S)), 12.17 (s, 1H, C=SNHCPh), 8.992-7.47 (8H,
Ar-H); 13C NMR (CDCl3) δ ppm: 180.4 (C=S); 171.3 (C=O);
145.2; 137.3; 134.2; 132.5; 131.3; 130.6; 130.2; 129.4; 128.1
(CAr); MS: 302, 138.
RESULTS AND DISCUSSION
N-Nicotinoyl-N'-(4-nitrophenyl) thiourea (3a) and N-
nicotinoyl-N'-(2-nitrophenyl) thiourea (3b) were easily
synthesized by reacting the corresponding aroyl isothiocyanates
with commercially available 4- or 2-nitroaniline in 84 % and
87 % yield (Scheme-I).
3,20
Sample 3a
I-
F-
2,5
2,0
OH-
Br-
Cl-
In the IR spectra of thiourea derivatives (3a and 3b), the
N-H stretching vibrations were observed at 3005 and 3335
cm-1 ν(N-H), as intense broad bands, respectively. The strong
ν(C=O) absorption bands appeared at 1673 and 1674 cm-1,
apparently decreasing in frequencies compared with the
ordinary carbonyl absorption (1710 cm-1). This was interpreted
as a result of its conjugation with the nicotinoyl ring and forma-
tion of intra-molecular hydrogen bonding with N-H. In
addition, the strong ν(C=S) absorptions band, appeared at 1283
and 1253 cm-1. The bands corresponding to the C-C stretching
vibrations of the nicotinoyl group were observed around 1423
and 1465 cm-1 for 3a and 3b, respectively. The bands at 1326
CN-
1,5
A
1,0
0,5
0,00
260,0 300
400
500
600,0
Fig. 1. UV-VIS absorption spectra of compound 3a (5 × 10-5 M) upon
addition of tetrabutylammonium fluoride, chloride, bromide, iodide,
cyanide and hydroxide (5 × 10-5 M) in DMSO

Vol. 25, No. 5 (2013)
Synthesis of Two Novel Aroyl Thioureas and Their Use as Anion Binding Receptors 2457
TABLE-1
SPECTRAL PARAMETERS (λmax) OF THE NEW AROYLTHIOURES UPON THE ADDITION OF
HYDROXIDE, CYANIDE AND HALIDES IONS IN DMSO SOLUTION
Sample
Only
OH-
516
CN-
394
F-
Cl-
Br-
I-
352
281
415
280
393
351
281
416
280
351
280
416
280
350
280
416
280
3a
516
416
280
416
280
3b
2,50
2,0
the chromophore (nitrophenyl). Upon the addition of fluoride
ions in increasing quantities, the peak at 352 nm first decreased
but that at 393 nm increased, which was ascribed to the charge
transfer (CT) between the anion binded-NH units and electron-
deficient-NO2 moiety at the para position, causing the
sensor solution to change from light yellow to bright yellow.
Obviously, there was one and only one well-defined isosbestic
point at 345 nm, which indicated that there existed only one
type of host-F- complex. (Fig. 5). The addition of OH- also led
to spectral changes (Fig. 6). Similarly, there were two well-
defined isosbestic points at 492 and 516 nm which indicated
that there existed two types of host-OH– complexes.
Sample 3b
OH-
1,5
I-
A
Br-
1,0
Cl-
F-
0,5
CN-
0,00
260,0
300
350
400
450
500
550
600,0
Fig. 2. UV-VIS absorption spectra of compound 3b (5 × 10-5 M) upon
addition of tetrabutylammonium fluoride, chloride, bromide, iodide,
cyanide and hydroxide (5 × 10-5 M) in DMSO
2,00
Host 3a
A drastic change, thus, the highest λmax shift, was caused
by OH- ions. The successive addition of OH- to DMSO solutions
of 3a, b resulted in quite significant changes in the absorbance
spectra (Figs. 3 and 4). The results of absorbance changes due
to H-binding of various anions such as F-, OH- (λmax) are shown
in Table-1.
----> F-
1,5
1,0
A
0,5
0,00
260,0 300
350
400
450
500
550,0
Fig. 5. UV-VIS spectral titration of 3a with F- (as its tetrabutylammonium
salt) in DMSO, from which the association constant was
determined15, log K = 4.3 0.13
Fig. 3. Changes in the colour of 5 × 10-5 M DMSO solution of receptor 3a.
From left to right, in the absence of ions, in the presence of
tetrabutylammonium anions; fluoride, chloride, bromide, iodide,
cyanide and hydroxide
2,50
2.0 eq OH-
Sample 3a
2,0
1,5
1,0
1 eq OH-
1.7 eq OH-
1.5 eq OH-
1.3 eq OH-
A
0,5
1.1 eq OH-
0,00
260,0
300
350
400
450
500
550
600,0
Fig. 6. UV-VIS spectral titration of 3a with OH- (as its tetrabutylammonium
salt) in DMSO, from which the two association constants were
determined15, log K1 = 5.53 0.24 and log K2 = 4.24 0.18
Fig. 4. Changes in the colour of 5 × 10-5 M DMSO solution of receptor 3b.
From left to right, in the absence of ions, in the presence of 1 equiv.
of tetrabutyl-ammonium anions; fluoride, chloride, bromide, iodide,
cyanide and hydroxide
Secondly, to explore more about the applicability of 3b
as a sensor for F- and OH- anions, UV-VIS titrations were
performed in DMSO. Upon the addition of hydroxide ion in
increasing quantities, the colour of the sensor solution changed
Fig. 5 shows the UV-VIS spectral changes of 3a during
titration with fluoride. The original absorbance peaks appeared
at λmax of 352 nm and 393 nm, i.e. the π-π* transition bands of

2458 Aydin et al.
Asian J. Chem.
from light yellow to red and the intensity of the peak at 415
nm decreased, but that at 516 nm increased, which was ascribed
to the charge transfer (CT) between the anion binded -NH
units and the electron-deficient-NO2 moiety at the ortho position.
In the presence of 1 equivalent amount of F-, no change in the
absorbance values was observed (Figs. 7 and 8).
ions in DMSO. It was proven that there was a strong hydrogen
binding interaction between fluoride anion and the two N-H
groups of these aroylthioureas by means of 1H NMR titration,
UV-VIS spectra or with naked-eyed change results.
1,76
2 eq F–
1,5
Sample 3b
1,0
-----> OH-
A
1 eq F–
0,5
0,02
260,0
300
350
400
450
500
550
600,0
3a
Fig. 7. UV-VIS spectral titration of 3b with OH- (as its tetrabutylammonium
salt) in DMSO solution, from which the association constant was
determined15, log K = 3.92 0.21
13
12
11
10
(ppm)
9
.8
07
2,40
Fig. 9. Partial 1H NMR (400 MHz) of 3a (1 mM) in DMSO-d6. Compound
2,0
----> F-
a only; 1+1 equiv of F-; 1+2 equiv of F-
1,5
ACKNOWLEDGEMENTS
A
1,0
Sample 3b
The financial support from Çanakkale Onsekiz Mart
University Grants Commission (Project Number: 2008/35) was
gratefully acknowledged. The authors also thank Hacettepe
0,5
1
University, Department of Chemistry for H NMR titration
experiments and MS analyses.
0,00
260,0
300
350
400
450
500
550
600,0
Fig. 8. UV-VIS spectral titration of 3b with F- (as its tetrabutylammonium
salt) in DMSO solution
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