The synthesis of vinyltriethoxysilane-modified heteroaryl thiazole dyes and silica hybrid materials

Article abstract of DOI:10.1016/j.dyepig.2009.12.006

Hybrid materials composed of tetraethoxysilane and heteroaryl 4-substituent-2-aminothiazoles were prepared. 4-Substituted acetophenone, thiourea and iodide were used to generate the intermediate, 4-substituted-2-aminothiazole, as coupling component, which was then coupled with p-nitroaniline and p-methoxyaniline to yield heteroaryl 4-substitued thiazole azo dyes. The dyes subsequently underwent hydrolytic polycondensation with vinyltriethoxysilane and tetraethoxysilane to yield hybrid, heteroaryl thiazole azo dyes, whose chemical structure was characterized using FT-IR, ²⁹Si NMR, ¹H NMR and EDS.

Full text of DOI:10.1016/j.dyepig.2009.12.006

Dyes and Pigments 86 (2010) 129e132
Contents lists available at ScienceDirect
Dyes and Pigments
journal homepage: www.elsevier.com/locate/dyepig
The synthesis of vinyltriethoxysilane-modified heteroaryl thiazole dyes
and silica hybrid materials
*
Ming-Shien Yen , Chien-Wen Chen
Department of Polymer Materials, Kun Shan University, Yung Kang, Tainan 71003, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Hybrid materials composed of tetraethoxysilane and heteroaryl 4-substituent-2-aminothiazoles were
prepared. 4-Substituted acetophenone, thiourea and iodide were used to generate the intermediate,
4-substituted-2-aminothiazole, as coupling component, which was then coupled with p-nitroaniline and
p-methoxyaniline to yield heteroaryl 4-substitued thiazole azo dyes. The dyes subsequently underwent
hydrolytic polycondensation with vinyltriethoxysilane and tetraethoxysilane to yield hybrid, heteroaryl
thiazole azo dyes, whose chemical structure was characterized using FT-IR, 29Si NMR, 1H NMR and EDS.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 27 August 2009
Received in revised form
28 November 2009
Accepted 17 December 2009
Available online 4 January 2010
Keywords:
VTES
TEOS
Thiazole
Azo dyes
Solegel
Hybrid
1. Introduction
In view of the aforementioned facts, the solegel method was
used to produce heteroaryl azo dyes via a blending reaction with
Multifunctional polymeric materials have been used for opto-
electronic polymer materials, composite materials, nanopolymer
materials [1] and biopolymer materials; some are even employed in
emerging fields of energy, medicine, biology and aviation. Organic/
inorganic hybrid materials have also been used to prepare multi-
functional polymeric materials [2e5]. Current methods for
preparing functional polymers can be divided into four categories
of preparation namely, using a functional monomer [6], by the
chemical reaction of a polymer [7], blending and compounding [8],
and (4) special processing or surface treatment [9]. The solegel
method [10,11], which is generally applied to functionalized silica
materials has been established in the synthesis of monodispersed
particles that control chemical reactions in homogeneous solutions
[12,13].
various proportions of vinyltriethoxysilane and tetraethoxysilane.
2. Results and discussion
2.1. Preparation of hybrid materials 10ae10c and 13ae13c
Scheme 1 presents the route for synthesizing diazo components
and bis-hetaryl monoazo dyes. The coupling components, 4-phenyl-
2-aminothiazole 7a and its derivatives 7be7c, used as starting
materials in the synthesis of the precursor hybrid materials, were
obtained by the cyclization of a mixture of p-phenylsubstituted-
acetophenone 2ae2c, thiourea 1 and iodide 3. As shown in Scheme
1, two series of new bis-hetaryl monoazo dyes, 8ae8c and 11ae11c,
based on 4-aryl-2-aminothiazoles as coupling components with
both diazo components p-nitroaniline and p-methoxyaniline, were
prepared. The diazo component p-nitroaniline was diazotized
using sulfuric acid at 0e5 ꢀC. Before the end of diazotization, the
sulphamic acid was added to a diazonium salt solution to remove
excess nitrite ions; the diazonium salt solution was then added to
an aqueous diluted sodium carbonate solution of coupling compo-
nents 7ae7c. To complete the coupling reaction, the pH value of
the mixture was adjusted from about 5 to 6 by adding 40%
sodium hydroxide solution, which promoted the precipitation of
the dyes. The presence of acetic acid prevented an abrupt increase in
Heteroaryl azo dyes [14,15] contain unshared electron pairs of
nitrogen and sulfur, which can trigger resonance and cause the
p
electron of the compound to move from the ground state to the
excited state. This process facilitates the chromogenic development
of the compound.
* Corresponding author. Tel.: þ886 6 2050349; fax: þ886 6 2050493.
E-mail address: yms0410@mail.ksu.edu.tw (M.-S. Yen).
0143-7208/$ e see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.dyepig.2009.12.006

130
M.-S. Yen, C.-W. Chen / Dyes and Pigments 86 (2010) 129e132
the hybrid materials with various VTES/TEOS ratios indicates that
increasing the TEOS concentration increases the absorption
strength of SieOeSi close to 1100 cmꢁ1 and strengthens the
bonding. The structure of SieOeSi was analyzed using by 29Si NMR.
R
N
S
O
I2
+
+
R
NH2
H2N NH2
S
CH3
3
2
7a-7c
2.3. Analysis of 1H NMR and 29Si NMR
1
7a R=Ph
7b R=p-Cl-Ph
7c R=p-OCH3-Ph
R1
NH2
Analysis of the 1H NMR spectrum analysis of the heteroaryl azo
dye 8ae8c, presented in Table 2, reveals that the diazo coupling of
the intermediates 7ae7c causes the eCH of dyes 8ae8c to be
replaced by an azo benzene ring. The benzene ring absorbs the
coupling
4
R
N
R1
Compd.
R
R1
N
N
S
multiplet of dye 8a at
positions of the benzene ring absorb the doublet at
the symmetric hydrogens, 2,6-Ph-H and 3,5-Ph-H, absorb the
d
¼ 7.39e7.55 ppm; the second and sixth
NH2
Ph
p-Cl-Ph
p-OCH3-Ph
Ph
NO2
NO2
8a 9a 10a
8b 9b 10b
8c 9c 10c
11a 12a 13a
11b 12b 13b
11c 12c 13c
d
¼ 7.71 ppm;
8a-8c, 11a-11c
NO2
doublets at
d
¼ 8.19 ppm and 8.28 ppm, respectively, and the singlet
¼ 8.98 ppm is absorbed by eNH2. Moreover, 29Si NMR [17] is
OCH3
OCH3
OCH3
at
d
OEt
p-Cl-Ph
p-OCH3-Ph
employed to observe the structure that is formed by the hydrolysis
of Si. While the FT-IR results indicate the formation of SieOeSi by
a solegel reaction, 29Si solid-state NMR gives further information
on the structure of silica and the extent of the SieOH condensation
reaction. In principle, high-resolution solid-state NMR spectra of
simple dyes and VTES can include absorption peaks at ꢁ70.51 ppm
(T2) and ꢁ80.17 ppm (T3), corresponding to SieOR following the
hydrolysis of VTES. The 29Si NMR figure of hybrid materials that are
formed with various molar VTES/TEOS are considered. At both
ꢁ69.49 ppm (T2) and ꢁ78.57 ppm (T3), as well as ꢁ101.14 ppm (Q3)
and ꢁ110.83 ppm (Q4), considerable absorption occurs. Adding of
TEOS increases, the intensity of the absorption peaks of Q3 and Q4 is
becoming more significant. The main peak, Q4, appeared at
ꢁ110.83 ppm adjacent to a minor peak at ꢁ101.14 ppm, Q3. The
strong Q4 revealed that the degree of silicon condensation was very
high.
OEt
CH2 CH Si
OEt
5
R
N
OEt
TEOS
R1
N
N
OEt
OEt
N
H
CH2 CH2
Si
S
6
9a-9c, 12a-12c
R
N
H2
C
R1
N N
O
N CH2
H
Si
O
Si O
O
S
O
O
Si
Si
10a-10c, 13a-13c
Scheme 1. Synthesis of the hybrid materials 10ae10c, 13ae13c.
2.4. EDS analysis of hybrid materials
pH [16]. Dyes 8ae8c were precipitated after the diazonium
solution was added, and were then filtered, washed and air-dried.
The synthesis of dyes 11ae11c was similar to that of dyes 8ae8c,
except that the diazo components were replaced by p-methox-
yaniline. Then, two series of new bis-hetaryl monoazo dyes,
8ae8c and 11ae11c, alternately modified by the addition of vinyl-
triethoxysilane at a constant ratio to yield precursors 9ae9c and
12ae12c, were prepared. Finally, two series of precursors, 9ae9c and
12ae12c, were synthesized alternately by condensation with tet-
raethoxysilane at a constant ratio to yield hybrid materials 10ae10c
and 13ae13c, were prepared.
Table 3 presents the EDS of the hybrid materials. The table
indicates that the weight of a dye/VTES/TEOS hybrid material
increases with the amount of TEOS because the Si(OH)3 structure
that is formed by hydrolysis-condensation of VTES and the SiO2
that is formed after the hydrolysis-polycondensation of TEOS are
combined with the dyes. The atomic content reveals that the Si
peak reveals a dyes/VTES/TEOS hybrid material becomes more
intense as the amount of TEOS increases.
2.5. Analysis of UV spectrum
2.2. FT-IR analysis of hybrid materials
Table 4 presents the results of the ultraviolet visible absorption
spectral analysis of each compound. The lmax values associated
with the mono-substituent follow the order 8c > 8a > 8b. Based on
this result, if the mono-substituent is a donor group, then its lmax is
assumed to increase. Meanwhile, the effect of the dyes bonding
precursor and the hybrid material on lmax is insignificant. Dyes
8ae8c and dyes 11ae11c with various diazonium components are
compared and lmax is found to vary with the substituent. A benzene
ring structure to which is bonded a nitro group diazonium
component as an acceptor group will prompt lmax to move toward
longer wavelength. Bonding a methoxy group substituent diazo-
nium component to a benzene ring reduces its lmax. The ultraviolet
visible absorption spectral analysis of hybrid materials with various
ratios of constituents demonstrates that increasing the number of
moles of any one constituent does not significantly affect lmax.
According to the spectra, which indicate the effect of different
solvents on the compound, dissolution in DMF increases lmax. Since
the dipole moment of THF is smaller than that of DMF, and that
a greater dipole moment induces resonance among molecules
The FT-IR figure of dyes and the hybrid materials indicates that
dyes 8a yields NeH group and CeH group absorption peaks close to
3440 cmꢁ1 and 3113 cmꢁ1, respectively. In the FT-IR figure of the
precursors 9a there is an obvious deviation of amino group
absorption peaks close to 3419 cmꢁ1 and absorption peaks around
3395 cmꢁ1, revealing that some of the dye had reacted with VTES.
The appearance of the SieOR absorption peak around 1096 cmꢁ1
proved that VTES could convert the primary amine group become
a secondary amine group: the absorption peak was around
3372 cmꢁ1. Therefore, reactions can be reasonably assumed to have
occurred between some of the dyes and VTES. The FT-IR figure of the
hybrid materials 10a includes the absorption peak of the converted
secondary amine. The strong capture of the SieO structure at
1065 cmꢁ1 proves the dissociation of the NH2 bond. The SieC bond
close to 1244 cmꢁ1 also reveals that following the dissociation of the
NH2 bond, bonding with CH2 result in linking the SieO bond and
prompts the formation of the SieOeSi network. The FT-IR figure of

M.-S. Yen, C.-W. Chen / Dyes and Pigments 86 (2010) 129e132
131
Table 2
more easily, less energy is required for dissolution in DMF than in
Spectral data of intermediates and dyes derivatives 7ae7c, 8ae8c, 11ae11c.
THF, and consequently the absorption wavelength is higher.
Dyes IR (KBr) (ppm)
n
(cmꢁ1 1H NMR (DMSO-d6)
)
d
7a
7b
eNH2 3425
eCH 3110
7.07 (1H, s, eCH), 7.20 (1H, s, eNH2), 7.26e7.79
(5H, m, ArH)
3. Experimental
All melting points are uncorrected and in ꢀC. FT-IR spectra were
recorded on a Bio-Red Digilab FTS-40 spectrometer (KBr); 1H NMR
spectra were obtained on a BRUKER AVANCE 400 MHz NMR spec-
eNH2 3431
eCH 3107
CeCl 727
7.06 (1H, s, eCH), 7.10 (1H, s, eNH2), 7.39
(2H, d, 2,6-ArH), 7.82 (2H, d, 3,5-ArH)
trometer, and chemical shifts are presented in
d
ppm using TMS as
7c
eNH2 3430
eCH 3112
OeCH3 1174
3.81 (3H, s, eOCH3), 7.04 (1H, s, eNH2), 7.70
(2H, d, 3,5-ArH), 7.76 (2H, d, 2,6-ArH)
an internal standard. The 29Si NMR spectra were collected using
a BRUKER AVANCE 400 MHz NMR spectrometer at 78.49 MHz, with
a recycle time of 60 s, and the number of scans is 914. Mass spectra
were obtained using a Finnigan TSQ-700 GC/LC/MS spectrometer.
SEM images were captured using a Philips XL40 FE-SEM. Electronic
spectra were recorded using a SHIMADZU UV-1201 from dyes
8a
8b
eNH2 3433
eCH 3057
7.04 (1H, s, eNH2), 7.51e7.55 (5H, m, ArH), 7.71
(2H, d, 2,6-Ph-H), 8.19 (2H, d, 3,5-Ph-H)
eNH2 3432
eCH 3105
CeCl 739
7.06 (1H, s, eNH2), 7.51 (2H, d, 2,6-ArH), 7.55
(2H, d, 3,5-ArH), 7.71 (2H, d, 2,6-Ph-H), 7.78
(2H, d, 3,5-Ph-H)
solutions in DMF and THF at a concentration of 1 ꢂ10ꢁ5 mol lꢁ1
.
8c
eNH2 3427
eCH 3086
OeCH3 1170
3.80 (3H, es, OCH3), 6.89 (1H, s, eNH2), 7.14
(2H, d, 3,5-ArH), 7.23 (2H, d, 2,6-ArH), 7.74
(2H, d, 3,5-Ph-H), 7.82 (2H, d, 2,6-Ph-H)
3.1. Material
11a
11b
eNH2 3430
eCH 3105
OeCH3 1179
3.80 (3H, s, eOCH3), 7.04 (1H, s, eNH2), 7.40e7.50
(5H, m, ArH), 7.61 (2H, d, 3,5-Ph-H), 7.82
(2H, d, 2,6-Ph-H)
Vinyltriethoxysilane, tetraethoxysilane, acetophenone, p-
methoxyacetophenone, p-chloroacetophenone and p-methox-
yaniline were purchased from Acros Co., Ltd., Belgium. Thiourea,
sulphamic acid, p-nitroaniline and iodide were purchased from
Hayashi Pure Chemical Co., Ltd.
eNH2 3430
eCH 3115
OeCH3 1181
CeCl 732
3.81 (3H, s, eOCH3), 7.06 (1H, s, eNH2), 7.22
(2H, d, 3,5-ArH), 7.43 (2H, d, 2,6-ArH), 7.62
(2H, d, 3,5-Ph-H), 7.76 (2H, d, 2,6-Ph-H)
3.2. Preparation of intermediates 7ae7c
11c
eNH2 3425
eCH 3110
3.80 (3H, s, eOCH3), 6.89 (1H, s, eNH2), 7.22
(2H, d, 3,5-ArH) 7.41 (2H, d, 2,6-ArH), 8.07
(2H, d, 3,5-Ph-H), 8.18 (2H, d, 2,6-Ph-H)
2-Amino-4-phenyl-thiazole (7a) was prepared from a mixture
of thiourea, acetophenone and iodide, as described elsewhere [18].
7be7c were synthesized by the same method as described for the
synthesis of 7a. Tables 1 and 2 present the physical and spectral
data of these compounds.
4-phenyl-2-aminothiazole 7a (2.0 g, 0.01 mol) and 10% sodium
carbonate was stirred. The diazonium mixture was added at 0e5 ꢀC
and the solution was stirred for at least 2 h, after which time, the pH
was raised to 5e6 (by adding aqueous sodium hydroxide or sodium
acetate). The ensuing mixture was filtered and washed in water to
neutral pH. The resulting product was filtered, washed with water
and recrystallized from ethanol to give dye 8a. Compounds 8be8c
and 11ae11c were synthesized by the same method as was used to
synthesize 8a that was coordinated with the various diazo
components. Tables 1 and 2 present the physical and spectral data
of these compounds.
3.3. Preparation of the dyes 8ae8c and 11ae11c
A finely ground powder of p-nitroaniline 4a (1.38 g, 0.01 mol)
was added to a mixture of 12 ml of hydrochloric and stirred for
20 min. Sodium nitrite (0.72 g, 0.0105 mol) was added in portions
to 5 ml of concentrated sulfuric acid at 10 ꢀC and stirred for 1 h at
60e65 ꢀC. The solution was cooled to below 5 ꢀC, and then the
finely ground derivatives were slowly added; the mixture was
stirred for an additional 1 h at 5e10 ꢀC until it was clear. The
resulting diazonium solution was used immediately in the coupling
reaction. A clear mixed solution of the coupling component
3.4. Preparation of the precursor 9ae9c and 12ae12c
Precursor 9a (also known as V3) was prepared by the reaction of
dyes 8a (3.25 g, 0.01 mol) followed by the addition of vinyl-
triethoxysilane (9.5 g, 0.05 mol) in 80 ml tetrahydrofuran with
stirring at 65 ꢀC for 4 h at an adjusted pH of 4e5. Precursors 9be9c
and 12ae12c were synthesized by the same method used to
prepare 9a.
Table 1
Characterization data for intermediates and dyes derivatives 7ae7c, 8ae8c, 9ae9c,
11ae11c and 12ae12c.
Compound
M.p.a (ꢀC)
MS (m/e,Mþ)
Yieldb (%)
Molecular formula
7a
7b
7c
8a
8b
8c
9a
9b
143e145
162e164
183e185
245e247
262e264
280e282
304e306
315e317
321e323
253e255
271e273
297e299
313e315
319e321
325e327
176
210
206
325
360
356
468
503
499
310
345
341
453
488
484
65
50
67
70
60
75
59
51
57
50
47
52
45
41
43
C9H8N2S
C9H7N2SCl
C10H10N2SO
C15H17N2SO2
C15H10O2N5SCl
C16H13N5SO3
C23H29N5SO2Si
C23H28N5SO2SiCl
C24H31N5SO3Si
C16H14ON4S
3.5. Preparation of hybrid materials 10ae10c and 13ae13c
Hybrid material 10a was prepared by the condensation of
precursor 9a (5.01 g, 0.01 mol) and tetraethoxysilane (2.08 g,
Table 3
9c
EDS analysis of hybrid materials.
11a
11b
11c
12a
12b
12c
C16H13ON14SCl
Compd.
Elemental composition (%)
C17H16O2N4S
C26H32N4SOSi
C26H31ON4SSi
C27H34O2N4SSi
C
N
O
Si
S
T1
T2
T3
T4
45.89
36.30
33.32
28.44
4.06
4.78
3.55
3.38
18.51
22.30
24.98
25.29
25.66
32.16
33.16
37.89
5.88
4.46
4.99
5.00
a
Recrystallized from ethanol.
Yield of crude product.
b

132
M.-S. Yen, C.-W. Chen / Dyes and Pigments 86 (2010) 129e132
Table 4
References
Visible absorption spectra of dyes, precursor and hybrid materials.
[1] Daoud Walid A, Xin John H, Tao Xiaoming. Synthesis and characterization of
hydrophobic silica nanocomposites. Applied Surface Science 2006;252:
5368e71.
Data
Dyes
lmax (nm)
Data
Dyes
lmax (nm)
DMF
THF
DMF
THF
[2] Haas Karl-Heinz. Hybrid inorganiceorganic polymers based on organically
modified Si-alkoxides. Advanced Engineering Materials 2000;2(9):571e82.
[3] Donescu Dan, Teodorescu Mircea, Serban Sever, Fusulan Liana, Petcu Cristian.
Hybrid materials obtained in microemulsion from methyl methacrylate,
methacryloxypropyltrimethoxysilane, tetraethoxysilane. European Polymer
Journal 1999;35:1679e86.
[4] Avila-Herrera CA, Gomez-Guzman O, Almaral-Sanchez JL, Yanez-Limon JM,
Munoz-Saldan J, Ramrez-Bon R. Mechanical and thermal properties of
SiO2-PMMA monoliths. Journal of Non-Crystalline Solids 2006;352:3561e6.
[5] Frings S, Meinema HA, van Nostrum CF, van der Linde R. Organic-inorganic
hybrid coatings for coating application based on polyesters and tetraethox-
ysilane. Progress in Organic Coatings 1998;33:126e30.
8a
8b
8c
9a
9b
9c
10a
10b
10c
510
505
524
506
510
514
511
514
523
499
497
518
495
497
510
501
505
515
11a
11b
11c
12a
12b
12c
13a
13b
13c
465
461
473
465
460
476
465
467
470
459
455
466
459
453
468
459
461
465
[6] Jesionowski T. Synthesis of organiceinorganic hybrids via adsorption of dyes
on an aminosilane-functionalised silica surface. Dyes and Pigments
2002;55:133e41.
[7] Senarath-Yapa Muditha D, Scott Saavedra S. Dyes leaching from a doped sol-
egel is eliminated by conjugation to a dendrimer. Analytica Chimica Acta
2001;432:89e94.
[8] Mah Sang Kook, Chung In Jae. Effects of dimethyldiethoxysilane addition on
tetraethoxysilane solegel process. Journal of Non-Crystalline Solids 1995;183:
252e9.
[9] Nassar Eduardo J, Neri Claudio R, Cale Paulo S, Serra Osvaldo A. Functionalized
silica synthesized by solegel process. Journal of Non-Crystalline Solids
1999;247:124e8.
0.01 mol), hydrochloric acid (0.365 g, 0.01 mol) and 5 ml of water in
80 ml tetrahydrofuran, with stirring at 65 ꢀC for 2 h. The hybrid
materials 10be10c and 13ae13c were synthesized using the
method described for 10a. The hybrid materials T1eT4 were
prepared using different molar ratios of precursor 9a:tetraethox-
ysilane of 1:1, 1:3, 1:5 and 1:10.
[10] Hench Larry L, West Jon K. The solegel process. Chemical Reviews 1990;90:
33e72.
4. Conclusions
[11] Lu Zhong-lin, Lindner Ekkehard, Mayer Hermann A. Applications of solegel-
processed interphase catalysts. Chemical Reviews 2002;102:3543e78.
[12] Gellermann C, Storch W, Wolter H. Synthesis and characterization of the
organic surface modifications of monodisperse colloidal silica. Journal of Sol-
gel Science and Technology 1997;8:173e6.
[13] Arkles B, Berry DH, Figge LK, Composto RJ, Chiou T, Colazzo H. Staged devel-
opment of modified silicon dioxide films. Journal of Sol-gel Science and
Technology 1997;8:465e9.
In this work, a series of heteroaryl 4-substituent thiazole dyes is
prepared. VTES/TEOS are added in various ratios to produce a series
of functional hybrid materials is produced by the solegel method.
The color of the series of dyes that contain the nitro group as the
diazonium component substituent is significantly deeper than that
of the series of dyes that have the methoxy group as the substit-
uent. FT-IR and NMR analysis confirms that the silicon in the hybrid
material can indeed bond with the thiazole dyes. Additionally,
ultraviolet spectral analysis reveals differences among different
solvents. The lmax values from the absorption spectra follow the
order DMF > THF.
[14] Hallas G, Choi JH. Synthesis and properties of novel aziridinyl azo dyes from 2-
aminothiophenes
e part 1: synthesis and spectral properties. Dyes and
Pigments 1999;40:99e117.
[15] Yen MS, Wang IJ. Synthesis and absorption spectra of hetarylazo dyes derived
from coupler 4-aryl-3-cyano-2-aminothiophenes. Dyes and Pigments 2004;61:
243e50.
[16] Yen MS, Wang IJ. A facile syntheses and absorption characteristics of some
monoazo dyes in bis-heterocyclic aromatic systems e part II: syntheses of 4-
(p-substituted) phenyl-2-(2-pyrido-5-yl and 5-pyrazolo-4-yl) azo-thiazole
derivatives. Dyes and Pigments 2004;63:1e9.
[17] Hook RJ. A 29Si NMR study of the solegel polymerisation rates of substituted
ethoxysilanes. Journal of Non-Crystalline Solids 1996;195:1e15.
[18] Pandeya SN, Sriram D, Nath G, DeClercq E. Synthesis, antibacterial, antifungal
and anti-HIV activities of Schiff and Mannich bases derived from isatin
derivatives and N-[4-(40-chlorophenyl)thiazol-2-yl] thiosemicarbazide. Euro-
pean Journal of Pharmaceutical Sciences 1999;9:25e31.
Acknowledgment
The authors would like to thank the National Science Council of
the Republic of China, Taiwan, for financially supporting this
research under Contract No. NSC-97-2622-E-168-010-CC3.