Mesoporous mixed metal oxide nanocrystals: Efficient and recyclable heterogeneous catalysts for the synthesis of 1,2-disubstituted benzimidazoles and 2-substituted benzothiazoles

Article abstract of DOI:10.1016/j.molcata.2011.03.027

Present communication elicits the use of mesoporous mixed metal oxide nanocrystals of Al₂O₃-Fe₂O₃, Al ₂O₃-V₂O₅ and Al₂O ₃-CuO as heterogeneous ca

Full text of DOI:10.1016/j.molcata.2011.03.027

Journal of Molecular Catalysis A: Chemical 341 (2011) 77–82
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Journal of Molecular Catalysis A: Chemical
journal homepage: www.elsevier.com/locate/molcata
Mesoporous mixed metal oxide nanocrystals: Efficient and recyclable
heterogeneous catalysts for the synthesis of 1,2-disubstituted benzimidazoles
and 2-substituted benzothiazoles
Prabal Bandyopadhyaya, Manisha Sathea, G.K. Prasada, Pratibha Sharmab, M.P. Kaushika,∗
a Defence R & D Establishment, Jhansi Road, Gwalior, 474002 M.P., India
b School of Chemical Sciences, Devi Ahilya University, Khandwa Road, Indore, 452001 M.P., India
a r t i c l e i n f o
a b s t r a c t
Article history:
Present communication elicits the use of mesoporous mixed metal oxide nanocrystals of Al2O3–Fe2O3,
Al2O3–V2O5 and Al2O3–CuO as heterogeneous catalysts for the preparation of series of medicinally signif-
icant 1,2-disubstituted benzimidazoles and 2-substituted benzothiazoles. These nanocrystalline catalysts
exhibited remarkable catalytic activity with a high substrate to catalyst weight ratio (20:1) to achieve
the synthetic targets in the range of yield 81–96%. The solvent-free microwave assisted synthesis of
these compounds was an advantageous way which resulted in excellent yields in much lesser time
(0.75–1.5 min) in comparison to conventional heating. The use of catalyst in eco-friendly green protocol
and its reusability up to four cycles with similar catalytic response are the unique features of the het-
erogeneous catalysis. This protocol provided greater selectivity, cost-efficiency, clean reaction profiles,
simple work-up procedure and high yields.
Received 1 November 2010
Received in revised form 25 March 2011
Accepted 29 March 2011
Available online 4 April 2011
Keywords:
1,2-Disubstituted benzimidazoles
2-Substituted benzothiazoles
Mixed metal oxide nanocrystals
Mesoporous
© 2011 Elsevier B.V. All rights reserved.
Heterogeneous catalysis
1. Introduction
tion of the intermediate radical formed after initial oxidative
coupling between thiophenols and aromatic nitriles [18]. How-
The chemistry of benzimidazole and benzothiazole structural
motifs has blossomed rapidly in diverse areas of medicinal chem-
istry owing to their potential involvement as key component
for various pharmacological activities [1–6]. The high profiles
of biological applications displayed by compounds associated
with benzimidazole and benzothiazole nuclei have prompted
extensive studies for their synthesis [7,8]. Most of the meth-
ods reported so far for the synthesis of benzimidazoles involves
the condensation of 1,2-phenylenediamines with carboxylic acid
derivatives [9] or aldehydes [10] in presence of strong acids
such as polyphosphoric acid or mineral acid or under oxida-
tive condition. The use of palladium [11] and copper-catalyzed
[12] intramolecular N-arylation starting from o-haloanilines has
also been reported as other alternative. Recently, the use of
SiO2/ZnCl2 [13], cerium (IV) ammonium nitrate (CAN) [14] as the
catalyst and solvent-free protocols [15] has been described. Con-
ventionally, 2-substituted benzothiazoles are synthesized by the
condensation of 2-aminothiophenol with carboxylic acid deriva-
tives [16]. 2-Aryl benzothiazoles can be prepared by direct coupling
of benzothiazoles with aryl bromides [17] or by the cycliza-
ever, most of these methods suffer from several bottlenecks such
as the requirement of drastic reaction conditions (strong acids,
high temperatures), prolonged reaction time, limitation of being
restricted to only aromatic aldehydes, use of toxic and expensive
reagents/catalyst, use of hazardous solvents, low yields, formation
of by-products and tedious work-up procedure. As a consequence,
search for new methods/reagents/catalysts to overcome these lim-
itations is still an important experimental challenge to synthetic
organic chemists.
Recent advances in nanotechnology have led to an increasing
demand for multifunctional materials. Highly ordered mesoporous
materials function as excellent catalysts owing to their high surface
area and surface functionalities. Thus, synthesis of ordered meso-
porous materials has attracted great deal of research interest in
the last few years [19]. Of late, we successfully explored the use of
mixed metal oxide nanocrystals for the decontamination of yper-
ite [20]. In continuation of our work on new synthetic strategies
[21,22], herein, we report the efficient application of mesoporous
mixed metal oxide nanocrystals of Al2O3–Fe2O3, Al2O3–V2O5 and
Al2O3–CuO as heterogeneous catalysts for the synthesis of pharma-
cologically significant 1,2-disubstituted benzimidazoles 3a–o and
2-substituted benzothiazoles 5a–n (Scheme 1) by the condensation
of 1,2-phenylendiamines 1 or 2-aminothiophenol 4 with aromatic
and aliphatic aldehydes 2, respectively.
∗
Corresponding author. Tel.: +91 751 234 3972; fax: +91 751 234 7542.
E-mail address: mpkaushik@rediffmail.com (M.P. Kaushik).
1381-1169/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2011.03.027

78
P. Bandyopadhyay et al. / Journal of Molecular Catalysis A: Chemical 341 (2011) 77–82
NH2
NH2
N
Mixed metal oxide naocatalyst
R
2 R-CHO
Thermal heating / MW
solvent or solvent-free
N
R
1
2
3a-o
NH2
SH
N
S
Mixed metal oxide naocatalyst
R'-CHO
R'
Thermal heating / MW
solvent or solvent-free
2
4
5a-n
Scheme 1. Synthesis of 1,2-disubstituted benzimidazoles (3a–o) and 2-substituted benzothiazoles (5a–n) using mixed metal oxide nanocatalysts.
2. Experimental
2.4. Catalytic activity: synthesis of 1,2-disubstituted
benzimidazoles and 2-substituted benzothiazoles
2.1. Materials
Method A: To a mixture of 1,2-phenylenediamine (0.108 g,
1 mmol) and aromatic/aliphatic aldehyde (2 mmol), catalytic
amount (0.0054 g, 5 wt% of 1,2-phenylenediamine) of mesoporous
mixed metal oxide nanocrystals (Al2O3–Fe2O3 or Al2O3–V2O5 or
Al2O3–CuO) was added using 2 mL of acetonitrile as solvent at room
temperature under stirring. The reaction progress was monitored
by TLC. After stirring for 10–45 min, under heating condition at
60 ◦C, the reaction mixture was cooled to room temperature and
it was dissolved in ethanol (10 mL) and then poured into ice-water
(30 mL). Ethyl acetate (10 mL) was added and the catalyst was sep-
arated out by filtration from the extraction mixture. The organic
extract was dried over anhydrous sodium sulfate and excess of
solvent was removed under reduced pressure so as to obtain the
product. It was then purified by column chromatography over sil-
ica gel using hexanes/EtOAc (9:1, v/v) as the eluting solvent system,
yielding the pure products.
Aluminium-sec-butoxide, vanadyl acetylacetonate, copper
acetylacetonate, iron acetylacetonate, 1,2-phenylendiamines,
2-aminothiophenol, various aromatic and aliphatic aldehydes
were purchased from Sigma–Aldrich, India.
2.2. Catalyst preparation
Mesoporous mixed oxide nanocrystals of Al2O3–Fe2O3,
Al2O3–V2O5 and Al2O3–CuO were prepared by aero gel process:
A 1000 mL round bottom flask was charged with aluminium-sec-
butoxide (10.0 g) under constant nitrogen flow. It was dissolved in
100 mL of butan-2-ol to form a clear solution. To this solution, cop-
per acetylacetonate/iron acetylacetonate/vanadyl acetylacetonate
was added and the solution was stirred for 2 h. Now a mixture of
500 mL of toluene and 150 mL of butan-2-ol was added and the
contents were allowed to stir for 30 min. To this solution, 2.0 mL
of ultrapure water was added and the stirring was continued
for overnight period in order to obtain the soft gel. This soft
gel was then transferred to a Parr autoclave which was flushed
initially with nitrogen and pressurized to 100 psi under continuous
shaking. The reactor was slowly heated to 300 ◦C and the pressure
raised to 1000 psi. As soon as the autoclave has acquired 300 ◦C the
reactor was vented to ambient pressure. The autoclave was then
allowed to cool and flushed with nitrogen. Mesoporous mixed
oxide alumina thus obtained was heated at 500 ◦C under vacuum
[23].
Method B: In
a typical procedure, aldehydes (2 mmol),
1,2-phenylenediamines (1 mmol), and the catalyst (5 wt% of 1,2-
phenylenediamine) were placed in a 10 mL glass tube under
solvent-free condition. The vessel was then sealed with a septum,
placed into the microwave cavity and irradiated under a constant
150 W magnetron output power (at 109 ◦C) for 0.75–1.5 min. After
allowing the mixture to cool to room temperature, the reaction ves-
sel was opened. It was dissolved in ethanol (10 mL) and then poured
into ice-water (30 mL). The product was then purified according to
that described in Method A.
An identical procedure for the synthesis of 2-substituted ben-
zothiazoles was employed using 2-aminothiophenol (0.11 mL,
1 mmol) and aromatic/aliphatic aldehyde (1 mmol) in the presence
of catalytic amount (5 wt% of 2-aminothiophenol) of mesoporous
mixed metal oxide nanocrystals of Al2O3–Fe2O3, Al2O3–V2O5 or
Al2O3–CuO under conventional heating condition (60 ◦C) as well
as under the influence of microwave irradiation at 150 W (at
109 ◦C).
2.3. Catalyst characterization techniques
XRD patterns were obtained in an X Pert Pro Diffractometer,
Panalytical, Netherlands, using Cu K␣ radiation. The Scherer for-
mula was used to calculate the crystallite size of the materials:
3. Results and discussions
(0.9ꢀ180)
B cos ꢁꢂ
3.1. Characterization of catalysts
Crystallite size =
Å
Synthesized nanocrystals were characterized by X-ray diffrac-
tion studies as per the patterns depicted in Fig. 1. In all the
diffraction patterns of Al2O3–Fe2O3 (a), Al2O3–V2O5 (b) and
Al2O3–CuO (c), broadened peaks centered at 19.3, 37.5, 39.2, 45.6,
60.5 and 66.6 typical of (1 1 1), (3 1 1), (2 2 2), (4 0 0), (5 1 1) and
(4 4 0) were observed. They can be attributed to the presence of ␥-
Al2O3 in the above materials. XRD data also represented that, these
materials are of less crystalline in nature and they had a completely
√
2
2
˚
where, B = (FWHM − 0.3 ) and ꢀ is X-ray wave length (1.54 A).
FWHM is full width half maxima of the peak and ꢁ is Bragg’s
angle.
FWHM was calculated from the peak having highest intensity
in all the samples using X Pert high score plus LTU software.
SEM-EDAX measurements were done on a FEI instrument. N2
BET measurements were done on ASAP 2020 of Micrometrics, USA.

P. Bandyopadhyay et al. / Journal of Molecular Catalysis A: Chemical 341 (2011) 77–82
79
In order to confirm this, crystallites size of Al2O3–Fe2O3,
Al2O3–V2O5 and Al2O3–CuO materials was determined by the
Scherrer equation. The values of crystallite size diameter were
found to be 4.2 nm, 6.4 nm, 3.7 nm for Al2O3–Fe2O3, Al2O3–V2O5
and Al2O3–CuO, respectively. Size of crystallites Fe2O3, V2O5 on
alumina could not be calculated due to the amorphous nature of
diffraction patterns. Materials were further characterized by scan-
ning electron microscopy (SEM) [Fig. 2 (a–c)]. Scanning electron
micrographs show the aggregates of nanocrystallites having size
less than 50 nm. These aggregates appeared to be formed from par-
ticles of size smaller than 50 nm as indicated by XRD data. These
nanoparticles were seemed to orient randomly in irregular fashion
to minimize the steric, electric charge repulsions thereby resulting
into a porous structure. It also seemed that, size of the aggregates
influenced the size of the voids. Larger sized particle formed larger
sized voids and smaller sized aggregates formed smaller sized
voids on aggregation. SEM data indicated that the aggregates of
Al2O3–Fe2O3, Al2O3–V2O5 and Al2O3–CuO were having the values
of void diameters ranging approximately between 10 and 50 nm.
These values come in the range of mesoporous materials.
c
b
a
20
40
60
80
2θ(º)
Fig. 1. XRD pattern of (a) Al2O3–Fe2O3, (b) Al2O3–V2O5 and (c) Al2O3–CuO.
In order to characterize and determine the porous structure
and the value of the surface area of Al2O3–Fe2O3, Al2O3–V2O5 and
Al2O3–CuO, N2 BET adsorption studies were performed. A type
IV isotherm with hysterisis curve was obtained by such nitrogen
adsorption isotherm (Fig. 3), which represents characteristic fea-
amorphous pattern due to particle size broadening. It is clearly
revealed from the literature that, with the broadening of XRD peaks
along with the emergence of relatively lower crystallinities are in
accordance to the lower crystallite size [24].
Fig. 2. SEM images of (a) Al2O3–Fe2O3, (b) Al2O3–V2O5 and (c) Al2O3–CuO.

80
P. Bandyopadhyay et al. / Journal of Molecular Catalysis A: Chemical 341 (2011) 77–82
Table 2
Effect of catalyst concentration for the synthesis of 1-benzyl-2-phenyl benzimida-
zole (3a).
Al2O3-CuO
1400
1200
1000
800
Al2O3-Fe2O3
Al2O3-V2O5
Entry
Catalyst conc. (wt%)
Reaction timea (min)
Yield (%)b
1
2
3
4
5
1
2.5
5
10
20
1.5
1.5
1.5
2.0
2.5
52
67
89
85
79
600
Reaction condition: The mixture of 1,2-phenylenediamine (1 mmol) and ben-
zaldehyde (2 mmol) with different concentration of catalyst was irradiated under
microwave.
400
200
a
All the reactions monitored by TLC.
b
Isolated yield.
0
0.0
0.2
0.4
0.6
0.8
1.0
Table 3
Recyclability of the catalyst for the synthesis of 1-benzyl-2-phenyl benzimidazoles
(3a).
Relative pressure (P/P0)
Fig. 3. Nitrogen adsorption isotherms.
Entry
Cycle
Yielda (%)
1
2
3
4
Cycle 1
Cycle 2
Cycle 3
Cycle 4
89
83
70
62
Al2O3
Al2O V2O5
Al2O3 Fe2O3
-CuO
1.5
-
Reaction condition: The mixture of 1,2-phenylenediamine (1mmol) and ben-
zaldehyde (2 mmol) with mixed metal oxide nanocrystals (5 wt% of 1,2-
phenylenediamine) was irradiated under microwave for 1.5 min.
-
a
1.0
0.5
0.0
Yields after consecutive cycles.
Due to broadening of diffraction peaks it was quite uncertain to
confirm the presence of Fe2O3 or V2O5 nanocrystals in the matrix
of Al2O3. Therefore, for this sake, samples were analyzed by energy
dispersive analysis of X-rays. Data was calculated as wt% of either
Al, or Fe or Cu or V or O. In Al2O3–Fe2O3 sample, 39.37 wt% of
Al, 34.65 wt% of O, 12.32 wt% Fe were observed. In Al2O3–V2O5,
38.21 wt% of Al, 28.12 wt% of O, 20.95 wt% V were observed. In
Al2O3–CuO, 31.28 wt% of Al, 41.82 wt% of O, 5.27 wt% Cu were
observed. It is inferred from these data that, either metal oxides
are forming small clusters of nanocrystallites that are located on
the surface of Al2O3 which are in close contact with each other and
form an interface with more number of active sites or they form
small crystallites that are mixed with Al2O3 in a uniform manner.
In order to investigate the optimum reaction conditions, a set
of control experiments on benzaldehyde and 1,2-phenylendiamine
was carried out in the presence of catalytic amount of each
of Al2O3–Fe2O3, Al2O3–V2O5 and Al2O3–CuO systems separately
under solvent-free conditions using MW irradiations. It was
observed that, all the three catalytic systems efficiently accelerated
the reaction towards the formation of desired product, although
Al2O3–Fe2O3 and Al2O3–V2O5 were found to be little superior over
Al2O3–CuO owing to their enhanced surface properties. The opti-
mum weight percentage of the catalyst was also studied (1, 2.5, 5,
10, 20 wt% of 1,2-phenylenediamine) and it was revealed that 5 wt%
of the catalyst was the optimum weight percentage. The results are
presented in Table 2.
100 200 300 400 500 600
Pore width (ºA)
Fig. 4. Pore size distribution data of (a) Al2O3–Fe2O3, (b) Al2O3–V2O5 and (c)
Al2O3–CuO.
Table 1
BET Surface area and pore volume values for Al2O3–Fe2O3, Al2O3–V2O5 and
Al2O3–CuO.
Sl. no.
Catalyst
BET surface area (m2/g)
Pore volume (cm3/g)
1.
2.
3.
Al2O3–Fe2O3
Al2O3–V2O5
Al2O3–CuO
376
384
418
1.00
1.10
1.38
ture of mesoporous materials. It is revealed from the isotherms
that materials possess cylindrical pores with opening at both the
ends. Furthermore, Al2O3–CuO was found to have more number of
pores than Al2O3–V2O5 or Al2O3–Fe2O3.
Surface area of these materials was found to be ranging from
376 to 418 m2/g. They exhibited meso and macroporosity with the
pore volume range from 1.0 to 1.38 mL/g. The pore size distribution
data is depicted in Fig. 4.
3.2. Reusability of the catalyst
The surface area and pore volume values obtained from
the above studies are presented in Table 1. Data indicate that
Al2O3–Fe2O3 exhibited wide meso-pore size distribution with
maxima centered at 7.1 nm, whereas, Al2O3–V2O5 and Al2O3–CuO
exhibited wide pore size distribution unlike Al2O3–Fe2O3. The
pores as understood perhaps were formed by aggregation of
nanocrystals. However, during the formation of nanocrystals of
Al2O3–Fe2O3, they nucleate, crystallize and aggregate in a man-
ner to create pores of 7.1 nm width. In case of Al2O3–V2O5 and
Al2O3–CuO, they possibly follow a different route of crystallization
and orientation followed by aggregation due to different symmetry.
At the end of the reaction, the catalyst was filtered off, washed
with mixture of hot ethanol and water, dried at 100 ◦C for 3 h, and
reused as such for subsequent experiments (up to four cycles) under
similar reaction conditions. It was noticed that yields of the product
remained comparable in these experiments (Table 3), and thereby
pointing the recyclability and reusability of the catalyst without
any significant loss in catalytic activity.
When the reaction was carried out with 1,2-phenylendiamine
and aldehyde in 1:1 molar ratio under microwave, then a mixture
of mono and di-substituted product were formed. But when 1:2
molar ratio was used then the desired 1,2-disubstituted benzimi-

P. Bandyopadhyay et al. / Journal of Molecular Catalysis A: Chemical 341 (2011) 77–82
81
Table 4
Synthesis of 1,2-disubstituted benzimidazoles (3a–o) using mixed metal oxide nanocatalysts.
Entry
R
Product
Timea (min)
Method A
Yieldb (%)
Method A
Method B
Method B
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
C6H5
4-MeC6H4
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
12
27
34
45
22
35
21
27
10
25
14
12
37
20
24
1.0
1.5
1.5
1.0
84
85
87
83
81
89
88
85
87
84
85
90
84
78
82
89
88
90
89
88
92
93
89
91
89
88
93
94
89
88
4-MeOC6H4
4-(Me)2NC6H4
4-(Me)3CC6H4
3-EtO-4-HOC6H3
4-FC6H4
5-Br-2-HOC6H3
3-NO2C6H4
4-F3COC6H4
3,4-Cl2C6H3
Furyl
1.0
1.25
0.75
1.5
1.5
0.75
1.0
1.0
0.75
1.0
C6H5CH CH
CH3-CH2-CH2
CH3-(CH2)4-CH2
1.0
Reaction condition: 1,2-phenylenediamine (1 mmol), benzaldehyde (2 mmol), mixed metal oxide nanocrystals (5 wt% of 1,2-phenylenediamine), CH3CN (2 mL) (for method
A).
a
All the reactions monitored by TLC.
Isolated yield.
b
Table 5
Synthesis of 2-substituted benzothiazoles (5a–n) using mixed metal oxide nanocatalysts.
Entry
Rꢀ
Product
Timea (min)
Method A
Yieldb (%)
Method A
Method B
Method B
1
2
3
4
5
6
7
8
9
10
11
12
13
14
C6H5
2-EtC6H4
4-HOC6H4
3,4,5-(MeO)3C6H2
4-EtOC6H4
4-EtO-3-MeOC6H3
4-(Me)2HCC6H4
4-BrC6H4
4-ClC6H4
5-Br-2-MeOC6H3
4-NO2C6H4
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
13
22
16
33
15
24
17
10
11
28
23
13
10
15
1.0
1.0
1.0
1.5
1.0
1.5
1.0
1.0
1.0
1.5
1.5
1.0
1.0
1.0
87
85
84
83
85
83
87
87
89
89
88
86
79
80
89
92
95
90
94
93
96
93
92
91
94
89
89
89
2-F3CC6H4
CH3-CH2-CH2
CH3-(CH2)4-CH2
Reaction condition: 2-aminothiophenol (1 mmol), benzaldehyde (1 mmol), mixed metal oxide nanocrystals (5 wt% of 2-aminothiophenol), CH3CN (2 mL).
a
All the reactions monitored by TLC.
Isolated yield.
b
dazole was formed with excellent selectivity and yields. However,
trace amount of monosubstituted product was also formed in some
cases, which was separated by column chromatography. Moreover,
by applying microwave dielectric heating, the reaction time was
significantly reduced with the increase in the product yield as com-
pared to conventional heating.
It is evident from the data in Tables 4 and 5 that, the proposed
synthetic procedure works well with mono, di (Table 4, entries 6,
8 and 11 and Table 5, entries 6 and 10) and even tri-substituted
(Table 5, entry 4) aryl aldehydes. The effect of substitution present
on aromatic aldehyde on the reaction rate and the overall yield
was also studied. As shown, a variety of benzaldehydes bearing
NH2
R
R
NH2
N
N
N
H
R
R
H
R
N
N
H
N
R
R
O
H
H
Surface hydroxyls
O
O
(Lewis/Bronsted
OH OH OH OH
OH OH
OH
OH OH
OH
OH OH O OH
Acid sites)
O M O M O M O M
M O M O M O M O
O M O M O M O M
M O M O M O M O
O M O M O M O M
M O M O M O M O
O M O M O M O M
M O M O M O M O
Fig. 5. Proposed mechanism for the synthesis of 1,2-disubstituted benzimidazoles.

82
P. Bandyopadhyay et al. / Journal of Molecular Catalysis A: Chemical 341 (2011) 77–82
Fig. 6. Mechanistic pathway for the preparation of 2-substituted benzothiazoles.
electron-donating (Table 4, entries 2–7 and Table 5, entries 2–9)
and electron-withdrawing substituents (Table 4, entries 8–11 and
Table 5, entries 10–12) were successfully employed to prepare
the corresponding benzimidazoles 3a–o and benzothiazoles 5a–n
derivatives in excellent yields. Furfural (Table 4, entry 12) and
cinnamyl aldehyde (Table 4, entry 13) also afforded the desired
products in excellent yields. Moreover, this synthetic strategy
was further extended to aliphatic aldehydes, viz., butyraldehyde,
heptanal to obtain the desired 1,2-disubstituted benzimidazoles
(Table 4, entries 14 and 15) and 2-substituted benzothiazoles
(Table 5, entries 13 and 14) in reasonably good yield.
Acknowledgements
We thank Dr. R. Vijayaraghavan, Director, DRDE, Gwalior for his
keen interest and encouragement. P. B is thankful to DRDO, New
Delhi, for financial support.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.molcata.2011.03.027.
In order to demonstrate the synthetic potential of this proto-
col the same procedure was extended for one-pot synthesis of
benzothiazole class of compounds. An overview of synthetic high-
lights delineating the synthesis of 2-substituted benzothiazoles is
depicted in Table 5.
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