Synthesis and salient chemosensing properties of a new thiazole-azo derivative

Article abstract of DOI:10.1016/j.tet.2017.07.050

A new hydroxy-benzene modified thiazole-azo derivative was synthesized and its chemosensing towards heavy metal ions (Na⁺, Al³⁺, K⁺, Ca²⁺, Mn²⁺, Fe²⁺, Ni²⁺, Cu²⁺, Zn

Full text of DOI:10.1016/j.tet.2017.07.050

Accepted Manuscript
Synthesis and salient chemosensing properties of a new thiazole-azo derivative
Guan-Yeow Yeap, Elango Hrishikesan, Yi-Huan Chan, Wan Ahmad Kamil Mahmood
PII:
S0040-4020(17)30801-3
10.1016/j.tet.2017.07.050
TET 28882
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 4 October 2016
Revised Date: 26 June 2017
Accepted Date: 27 July 2017
Please cite this article as: Yeap G-Y, Hrishikesan E, Chan Y-H, Kamil Mahmood WA, Synthesis and
salient chemosensing properties of a new thiazole-azo derivative, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.07.050.
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ACCEPTED MANUSCRIPT
Synthesis and salient chemosensing properties of a new thiazole-azo
derivatives
Guan-Yeow Yeap*, Elango Hrishikesan, Yi-Huan Chan and Wan Ahmad Kamil Mahmood
Liquid Crystal Research Laboratory, School of Chemical Sciences, Universiti Sains Malaysia,
11800 Minden, Penang, Malaysia.
Graphical abstract

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Synthesis and salient chemosensing properties of a new thiazole-azo derivative
Guan-Yeow Yeap*, Elango Hrishikesan, Yi-Huan Chan and Wan Ahmad Kamil Mahmood
Liquid Crystal Research Laboratory, School of Chemical Sciences, Universiti Sains Malaysia,
11800 Minden, Penang, Malaysia
ABSTRACT
A new hydroxy-benzene modified thiazole-azo derivative was synthesized and its
chemosensing towards heavy metal ions (Na+, Al3+, K+, Ca2+, Mn2+, Fe2+, Ni2+, Cu2+, Zn2+, Ag+,
Cd2+, Hg2+ and Pb2+) was characterized by UV–vis spectroscopy. The newly obtained compound
produced cation-induced bathochromic shifts for Hg2+ ion more than the other tested metal ions
in acetonitrile solution. The interactions with cations were further studied by colorimetric, UV–
vis and NMR studies. The presence of the hydroxyl moiety along with the electron rich nitrogen
of thiazole ring acting as the binding site and the azo group acting as a signaling unit enables the
system to display excellent sensitivity for Hg2+ with a color change from light orange to red
purple. The stoichiometric ratio and the association constant for the complex between Hg2+ and
the target compound assume the values of 1:1 and 2.1 ×105 mol−1dm3, respectively.
Keywords: thiazole-azo conjugate, chemosensor, stoichiometric ratio, colorimetric, UV-vis
Corresponding author: G.Y.Yeap. Fax: +60 4 6534075.
E-mail address: gyyeap@usm.my
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1.
Introduction
Metal cations are essential in chemical, biological and environmental processes which
necessitate the recognition of these species through different techniques. The qualitative and
quantitative determination of metal ions present in biological and environmental systems are of
current interest particularly in the field of supramolecular chemistry.1-3 Hence, numerous organic
chemosensors have been developed by various research groups to selectively detect and
determine cations based on various sensing mechanisms.4-5
It is essential to design and synthesize specific colorimetric sensors for selective detection
of toxic metal ions in the environment. The design of such optical probes often involves the
selective construction of a binding unit in a chromophore with specific binding properties.
Results can then be easily obtained by observing colorimetric responses once the binding event is
accomplished with the probe and the photo-physical behavior of the chromophore is altered.
Various organic dyes have been used as signaling units in the development of colorimetric
sensors owing to the convenient synthesis and the well-known spectroscopic properties of these
substances.6
Earlier studies by coupling azobenzene chemosensors with electron rich bis-triazole and
bis-pyridine units to enable chemosensing behaviour with the Cu2+ ion had been elucidated by
naked eye detection method, but it had disadvantages due to the hypsochromic shift in
wavelength.7-8
Apart from Cu2+, other ions such as Zn2+, Fe2+, Mn2+, Ag+ and Ca2+ are also essential in
biological systems as endorsed by World Health Organization (WHO). The excessive
concentration of metals may lead to acute and chronic toxicity to all living organism.9 The
adverse effect due to prolonged exposure to these metals can be exemplified by mercury which
could lead to liver and kidney failure, cardiovascular disease and neurological disorder.10 As
such, the detection of Hg2+ is of great importance and deserves to be developed using various
techniques. One such technique is to develop colorimetric chemosensors for Hg2+ - this remains
very rare.11-12
In the present work, the synthesis of a thiophenol-based azobenzene chemosensor for
sensing of Hg2+ ions in acetonitrile medium is the focus. Thiazole is well-known for its chelation
towards metal ions including Hg2+, Zn2+ and Al3+ owing to the electron rich endocyclic N and S
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atoms. In addition this system has exocyclic O atom from phenol groups which have potential to
bind to metal ions.13-16
2.
Results and Discussion
The general synthetic route to form thiazole-azo conjugate (LI) is summarized in Scheme
1. The synthesis of 2-hydroxythiazoleamine was achieved by the reaction of 2-
hydroxyacetophenone with thiourea in refluxing ethanol, catalyzed by iodine, to get the product
with 68% yield. The resulting mixture was then diazotized in the presence of sulfuric acid and
sodium nitrite to condense with resorcinol and sodium acetate in order to achieve the desired
final product with 35% yield. The synthesized precursors and final compound L1 were
characterized by FT-IR, 1H- and 13C-NMR.
NH2
I2
OH
O
S
OH
N
S
H2N
NH2
NaNO2/H2SO4
OH
HO
N
N
N
HO
OH
OH
N
N
S
S
OH
N
CH3COONa
Scheme 1: Synthesis of compound L1
2.1
Photophysical studies of chemosensing molecule L1
The photo-physical behavior of L1 was investigated with several metal cations including
Na+, Al3+, K+, Ca2+, Mn2+, Fe2+, Ni2+, Cu2+, Zn2+,Ag+, Cd2+, Hg2+ and Pb2+ in the form of
perchlorate salts in CH3CN by using UV-Vis spectroscopy. The absorption spectrum of L1 alone
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has absorption maxima at 350 and 465 nm. The absorption at 465 nm is assigned to n-π*
transition of azobenzene chromophore by their strong push-pull effect17-18, and the absorption at
350 nm is assigned to the π- π* transition of the thiazole ring. Fig. 1 indicates absorption spectral
changes of L1 in CH3CN upon addition of various competitive metal ions. From UV-Vis spectra
of L1, a new absorption band centered at 490 nm can be clearly observed in the presence of 5
equiv of Hg2+ ion with distinct color change from orange to dark purple (Fig. S1†). However,
there were no appreciable spectral changes was observed upon addition of competitive metal
cations in absorption, which indicates the sensitivity of L1 for Hg2+ ion over other competitive
cations in the aqueous medium is on the high end.
L1
Na+
Al3+
K+
1.5
Ca2+
Mn2+
Fe2+
Ni2+
1.0
Cu2+
Zn2+
Ag+
Cd2+
Hg2+
Pb2+
0.5
0.0
200
300
400
500
600
700
Wavelength (nm)
Figure 1. 1 UV-Vis absorption spectra of L1 [1x10-5 M in CH3CN] in the presence of different
cations (5 equiv.)
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1.5
1.0
0.5
0.0
200 µm
465 nm
490 nm
Hg2+
0 µm
476 nm
200
300
400
500
600
700
Wavelength (nm)
Figure 2.
200µM) in CH3CN medium.
UV-Vis absorption spectra of L1 with increasing concentration of Hg2+ (0-
On titration with increasing concentration of Hg2+ the absorbance peak at 465 nm of L1
decreased while a new red shifted absorption band at 490 nm appeared gradually which
accompanied a clear isobestic point at 476 nm. This observation indicates that complexation has
occurred between L1 with Hg2+ (Fig. 2). The absorption maximum attained saturation at 490 nm
with the addition of 5 equiv. of Hg2+ and a gradual decrease in absorption band at 465 nm reveals
that the azobenzene took part in the coordination. Stoichiometric analysis of the complex
between L1 and Hg2+ was performed by means of continuous variation using Job’s method19
where the absorption of complex at 490 nm was plotted against mole fraction of L1 under the
condition of an invariant total concentration. Job’s plot depicts a maximum absorption center at
0.5 mole fraction of Hg2+, which supports 1:1 complex thus formed between L1 and Hg2+ (Fig.
3) with binding constant at 2.1 ×105 mol−1dm3 . The detection limit of L1 with Hg2+ was
calculated as 1.2x10-5 M.
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0.20
0.15
0.10
0.05
0.00
0.0
0.2
0.4
0.6
0.8
1.0
2+
[L1]/{[L1]+[Hg ]}
Figure 3. Job’s plot of a 1:1 complex for L1 and Hg2+ in CH3CN
To get more insight into the complexation behavior of L1 with Hg2+, FT-IR and 1H-NMR
studies were performed by adding different equivalents of Hg2+ with L1. Coordination sites of
compound L1 with Hg2+ can clearly be identified from 1000 to 3000 cm-1. In IR spectra (Fig. 4),
the stretching frequency of the imine group (C=N) within the thiazole ring of L1 appears at 1622
cm-1. However, this frequency was shifted to 1599 cm-1 when coordinated to Hg2+. This
observation can probably be ascribed to the transfer of electron density from imine N atom to
Hg2+ ion leading to a considerable decrease in effective positive charge on imine bond. Similarly,
a medium band at 1530 cm-1 of phenolic oxygen from azobenzene is shifted to 1508 cm-1 upon
complexation suggesting the coordination of newly derived L1with Hg2+ ion.
1H-NMR technique was used to further elucidate the coordination site of L1 for Hg2+.
Fig. 5 establishes the stacked plots of 1H-NMR spectra of L1 (10 mM) in the absence as well as
in the presence of various equivalents of Hg2+. All individual proton signals of L1 have been
assigned before and after complexation with Hg2+. The peak at 11.29 ppm corresponding to the
hydroxyl (OH) proton in the 2-thiazolephenol fragment disappeared while the intensity of the
other peak assignable to ortho-OH proton in the azobenzene at 10.94 ppm decreased upon the
addition of 1 equivalents of Hg2+. This observation indicates that the presence of new
coordination mode of Hg-O.
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100
90
80
70
60
50
40
30
20
10
0
1533
2850
3102
2932
1470
1508
3150
1622
1599
L1
L1+Hg2+
1029
1000
4000
3500
3000
2500
2000
1500
Wavenumber(cm-1)
Figure 4.
FT-IR spectra of L1 with Hg2+ ion.
A comparison between the chemical shifts of ortho- and para-OH from the azobenzene
unit before and after complexation shows that the interaction between Hg2+ with the ortho-
substituted OH is more effective than that at the para position. The resonances of other aromatic
peaks experience merely slight shifts indicating slight delocalization of electron densities in L1.
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Figure 5.
Partial 1H-NMR in DMSO-d6: (i) L1 only, (ii) L1 + 0.25 equiv. of Hg2+, (iii) L1 +
0.5 equiv. of Hg2+ and (iv) L1 + 1 equiv. of Hg2+
3.
Conclusion
A new compound L1 consisting of a thiazole-azo conjugate has been successfully
synthesized and its naked-eye sensing ability with Hg2+ studied by colorimetric techniques. The
binding site involved the coordination of the ortho-hydroxyl oxygen atom from respective
phenol-thiazole and azobenzene fragments. The addition of Hg2+ in different equivalents
produced the color change from light orange to dark purple by the increase in internal charge
transfer mechanism in azobenzene chromophore which can clearly be identified by the naked-
eye.
4.
Experimental
4.1
Materials and methods
All reagents were obtained commercially for synthesis and used without further
purification. 2-Hydroxyacetophenone, sodium acetate, resorcinol were purchased from Sigma
Aldrich, In the titration experiments, all cations were added in the form of perchlorate salts (Na+,
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Al3+, K+, Ca2+, Mn2+, Fe2+, Ni2+, Cu2+, Zn2+, Ag+, Cd2+, Hg2+ and Pb2+) which were purchased
1
from Sigma-Aldrich. H-NMR spectra were recorded on a Bruker 500 MHz spectrometer in
DMSO-d6. FT-IR spectra were measured on a Perkin-Elmer 2000 FTIR spectrophotometer
(Waltham, MA, USA). UV–Vis spectra were recorded in a 1 cm path length quartz cell on a
Shimadzu UV- 2600 spectrophotometer. Thin layer chromatography (TLC) was conducted on
silica gel 60 F254 plates (Merck KGaA).
4.2
Synthesis of 2-(2-aminothiazol-4-yl)phenol
In a round-bottom flask, 2-(2-aminothiazol-4-yl)phenol was prepared by reacting 2-
hydroxyacetophenone (1 g, 7.34 mmol), thiourea (1.12 g, 14.68 mmol) and iodine (1.86 g, 7.34
mmol) mixed with ethanol (20 mL) and refluxed overnight in an oil bath. The obtained mixture
poured into ice-cooled water and extracted with diethyl ether (3x50 ml). The organic layer was
washed with aqueous sodium thiosulfate to remove excess iodine and concentrated. The crude
1
product was recrystallized from ethanol. H-NMR (500 MHz, CDCl3) δ (ppm): 11.54 (s, 1H),
7.53 (dd, 1H, Ar-H), 7.20 (m, 1H, Ar-H), 6.96 (dd, 1H, Ar-H), 6.84 (m, 1H, Ar-H), 6.74 (d, 1H,
Ar-H), 5.07 (s, 2H, NH2) 13C NMR (125 MHz, CDCl3: Me4Si) δ (ppm): 173.61, 165.10, 159.59,
147.78, 133.07, 131.57, 125.67, 123.19, 120.98 and 101.66 (aromatic).
4.3
Synthesis of 4-((4-(2-hydroxyphenyl)thiazol-2-yl)diazenyl)benzene-1,3-diol (L1)
In a round-bottom flask, 2-(2-aminothiazol-4-yl)phenol (0.5 g, 2.6 mmol) was dissolved
with conc. H2SO4 (5 mL) and stirred below 5 0C and sodium nitrite (0.21 g, 3.1 mmol) was added
over 1 hour. Then the resulting diazotized salts were added dropwise into a round bottom flask
that contained resorcinol (0.29 g, 2.6 mmol) and sodium acetate (0.5 g, 6 mmol) dissolved in
ethanol with constant stirring until a dark red precipitate appeared. The reaction mixture was
further filtered through a Buchner funnel and dried. The crude product was subjected to column
chromatography using hexane/ethylacetate (2:1) as eluent to obtain an dark red solid as product
(0.25 g, 0.8 mmol, 35%). FT-IR (KBr, cm-1): 3102 (O-Hthiazole), 1622 (C=N), 1533 (O-Hazobenzene),
1470 (N=N). 1H NMR (500 MHz, DMSO-d6) δ (ppm): 11.29 (s, 1H, Ar-OH), 10.92 (s, 1H, Ar-
OH), 10.49 (s, 1H, Ar-OH), 8.40 (d, 1H, Ar-H), 8.15 (s, 1H, Ar-H), 7.95 (m, 1H, Ar-H), 7.66 (m,
13
1H, Ar-H), 7.19-7.11 (m, 2H, Ar-H), 6.87 (m,1H, Ar-H), 6.42 (m, 1H, Ar-H) . C-NMR (125
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MHz, DMSO-d6) δ (ppm): 174.80, 165.33, 158.56, 155.07, 151.23, 132.86, 129.28, 128.36,
119.65, 119.33, 117.51, 116.44, 110.08, 103.14 and 99.49 (aromatic).
Acknowledgments
The main author (G.-Y.Yeap) gratefully acknowledges Malaysian Ministry of Higher Education
(MOHE) for funding this project through FRGS Grant No.203/PKIMIA/6711422.
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