Metal acetylacetonates covalently anchored onto amine functionalized silica/starch composite for the one-pot thioetherification and synthesis of 2H-indazoles

Article abstract of DOI:10.1007/s10562-014-1345-y

This paper reports a series of novel metal acetylacetonates covalently anchored onto amine functionalized silica/starch composite, prepared by the Schiff condensation of metal acetylacetonates [Co(acac)₂, Cu(acac)₂, Pd(acac)₂, Ru(acac)₃, Mn(acac)₃, Co(acac)₃] with organically modified 3-aminopropyl silica/starch composite. Different metal acetylacetonates have been chosen with a view to select the most active heterogeneous catalyst. Among various catalysts, covalently anchored Cu(acac)₂ onto amine functionalized silica/starch composite [ASS-Cu(acac)₂] was found to be the most active and recyclable catalyst for the one-pot thioetherification and one-pot three component synthesis of 2H-indazoles via consecutive C-N and N-N bond formations. All the catalysts were characterized by FTIR, TGA and AAS analysis and the most active catalyst, [ASS-Cu(acac)₂] was further characterized by SEM and TEM. The catalyst could be recovered by simple filtration and reused with almost consistent activity for four consecutive runs.

Full text of DOI:10.1007/s10562-014-1345-y

Catal Lett (2014) 144:1819–1831
DOI 10.1007/s10562-014-1345-y
Metal Acetylacetonates Covalently Anchored onto Amine
Functionalized Silica/Starch Composite for the One-Pot
Thioetherification and Synthesis of 2H-Indazoles
Ravinderpal Kour Sodhi
Satya Paul
•
Avtar Changotra
•
Received: 22 May 2014 / Accepted: 21 August 2014 / Published online: 5 September 2014
Ó Springer Science+Business Media New York 2014
Abstract This paper reports a series of novel metal acet-
ylacetonates covalently anchored onto amine functionalized
silica/starch composite, prepared by the Schiff condensation
of metal acetylacetonates [Co(acac) , Cu(acac) , Pd(acac) ,
chemical industry with significant economic and environ-
mental impact [1–9]. In recent years, the emphasis of sci-
ence and technology is shifting more towards
environmentally friendly and sustainable resources, and
processes. The preparation of porous materials from
renewable resources such as starch is a relatively new area
and its applications are developing, mainly as a conse-
quence of a demand for biodegradable and naturally-
derived products [10, 11]. Developing applications of
biomaterials include new support materials for catalysts, as
support for sensors and nano-materials for microbial cul-
ture. The use of biopolymers as support material for metal
catalyst has attracted a wide attention in 1990’s, however
their application in organic syntheses started only in 2000
but this has been growing steadily ever since. Nowadays,
catalysts based on silica/biomaterial composites are being
used to meet the practical catalytic requirements in the
chemical industry. The combination of high surface area
inorganic mesoporous materials with organic polymer
systems is an emerging class of hybrid materials with
numerous potential applications [12–18]. They combine
the advantages of inorganic material (rigidity, thermal
stability) and the organic polymer (e.g., flexibility, ductil-
ity, and processability). Furthermore, these systems often
possess the capability for recovery, high activity, selec-
tivity, good accessibility and chemical versatility which is
an important factor for the development of green catalysts.
Despite of these potentialities, only few catalytic systems
have been reported using silica/biomaterial supported
metal as heterogeneous catalysts [19–21].
2
2
2
Ru(acac) , Mn(acac) , Co(acac) ] with organically modified
3
3
3
3
-aminopropyl silica/starch composite. Different metal
acetylacetonates have been chosen with a view to select the
most active heterogeneous catalyst. Among various cata-
lysts, covalently anchored Cu(acac) onto amine function-
2
alized silica/starch composite [ASS-Cu(acac) ] was found to
2
be the most active and recyclable catalyst for the one-pot
thioetherification and one-pot three component synthesis of
2
H-indazoles via consecutive C–N and N–N bond forma-
tions. All the catalysts were characterized by FTIR, TGA and
AAS analysis and the most active catalyst, [ASS-Cu(acac)2]
was further characterized by SEM and TEM. The catalyst
could be recovered by simple filtration and reused with
almost consistent activity for four consecutive runs.
Keywords Metal acetylacetonates Á Amine
functionalized silica/starch composite Á Thioetherification Á
2
H-indazoles Á Heterogeneous catalysis Á Recyclability
1
Introduction
Heterogeneous catalysis for the synthesis of fine chemicals
is an attractive area of research playing a crucial role in the
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-014-1345-y) contains supplementary
material, which is available to authorized users.
The construction of C–S bond represents an indispens-
able tool for the synthesis of new drugs and functionalized
moieties [22]. The preparation of thioethers has been under
consideration and widely studied in recent years using pal-
ladium [23], nickel [24], cobalt [25], copper [26] and iron
R. K. Sodhi Á A. Changotra Á S. Paul (&)
Department of Chemistry, University of Jammu,
Jammu 180 006, India
e-mail: paul7@rediffmail.com; paul7satya@yahoo.com
123

1
820
R. K. Sodhi et al.
salts [27] as catalysts. Migita et al. [28] first reported the
coupling of aryl halides with thiols using Pd(PPh ) as a
2 Experimental
3
4
catalyst. Recent methodologies include general protocols by
Zheng et al. using aryl triflates [29], coupling using DPE-
Phos as ligand [30]; thioetherification using CyPF-t-Bu as
ligand [23]. However, the harsh reaction conditions such as
high temperature, use of strong bases, stoichiometric
amounts of metal salts, and long reaction times are some of
the disadvantages of such protocols. Bhaumik et al. have
developed a novel protocol for one-pot thioetherification of
different aryl halides with thiourea in water [31]. Thus,
designing an efficient and environmentally friendly catalytic
process for C–S coupling reactions is highly desirable.
In heterocyclic chemistry, indazole unit has been rec-
ognized as a ‘‘privileged structure’’, and is an important
pharmacophore in medicinal chemistry [32–35]. 2H-Inda-
zoles are less studied as compared to 1H-indazoles due to
the difficulty in their preparation [36]. Hence, the forma-
tion of 2H-indazoles still remains a challenging task.
Recently, several promising synthetic routes have been
developed for the synthesis of 2H-indazoles, such as pal-
ladium-catalyzed intramolecular amination of the corre-
sponding N-aryl-N-(o-bromobenzyl) hydrazines [37]; Fe-
catalyzed intramolecular N–N bond formation from aryl
azides [38]; reaction of highly functionalized zinc reagents
with aryldiazonium salts [39]; [3 ? 2] dipolar cycloaddi-
tion of arynes and sydnones [33]; reaction of sodium
hydride or DBU catalyzed 2-nitrobenzyl triphenylphos-
phonium bromide with aryl isocyanates [40]; synthesis of
2.1 General Remarks
The chemicals used were either prepared in our laboratory
or purchased from Aldrich Chemical Company or Merck.
Metal acetylacetonates used for the preparation of catalyst
1
were purchased from Aldrich Chemical Company. The H
1
and C NMR spectra were recorded in CDCl or DMSO-
3
3
d6 on Bruker Avance III 400 MHz spectrometer. The FTIR
spectra were recorded on Perkin-Elmer FTIR spectropho-
tometer and mass spectral data were recorded on Bruker
Esquires 3000 (ESI). SEM images were taken on FEG
SEM JSM-7600F Scanning electron microscope and
Transmission electron micrographs (TEM) on H7500 Hit-
achi. The amount of metal in catalysts was determined by
AAS analysis and thermal analysis was carried out on
Linsesis STA PT-1000 make thermal analyzer. The CHNS
elemental analysis was carried out on Vario MICRO Cube.
Microwave synthesizer used was manufactured by CEM
(DISCOVER SYSTEM) and products were purified using
Flash chromatography (BIOTAGE).
2.2 General Procedure for the Synthesis of Amine
Functionalized Silica/Starch-M(acac)n
[ASS-M(acac)n]
Activated silica (5 g) was charged to the three-neck flask
(100 mL), equipped with a dropping funnel containing
thionyl chloride (20 mL) and a gas inlet tube for con-
ducting HCl over an absorbing solution of 10 % aqueous
NaOH. Thionyl chloride was added drop-wise over a per-
iod of 15 min at room temperature followed by stirring for
2
H-indazoles using Suzuki–Miyaura and Sonogashira
couplings [41]. However, most of the existing methods
exhibit several drawbacks, such as requirement of addi-
tives, low functional group tolerance; and need several
steps to synthesize the starting materials. Furthermore,
most of these methods are homogeneous in nature.
Therefore, there is a need for the development of novel and
selective approach for the synthesis of 2H-indazoles.
In this paper, we report the synthesis of different metal
acetylacetonate complexes covalently anchored onto amine-
functionalized silica/starch composite [ASS-M(acac)n,
n = 2 or 3, M=Co, Cu, Pd, Mn, Ru] and their catalytic
activities were evaluated for the one-pot thioetherification of
aryl halides with benzyl bromide and thiourea, and one-pot
three component synthesis of 2H-indazoles from 2-bromo-
benzaldehyde, primary amines and sodium azide through
consecutive C–N and N–N bond formations, with a view to
select the most effective recyclable and stable heterogeneous
catalyst. These heterogeneous catalysts were developed via
surface functionalization with 3-aminopropylsilica/starch
composite, followed by Schiff condensation of the surface
10 h at 80 °C. The untreated SOCl was removed by dis-
tillation and the resulting silica chloride was vacuum dried
2
at 90 °C [42].
Silica/starch composite was prepared by refluxing mix-
ture of silica chloride (5 g), corn starch (2 g), and triethyl
amine (0.5 mL) in CHCl (30 mL) for 10 h. The reaction
3
mixture was filtered, washed with chloroform (3 9 10 mL)
and water (3 9 20 mL) followed by drying in the oven at
120 °C for 2 h. To silica/starch composite (5 g) in dry tol-
uene (100 mL), 3-aminopropyl(trimethoxy) silane (0.89 g,
5 mmol) was added and the reaction mixture was refluxed for
12 h. The 3-aminopropylsilica/starch substrate was filtered
off, washed with hot toluene (50 mL) and dried at 110 °C for
5 h to get the surface bound amino groups.
For the preparation of amine functionalized silica/starch-
M(acac) , a mixture of 3-aminopropylsilica/starch substrate
n
(3 g) and M(acac) [0.5 mmol, 0.12 g Co(acac) , 0.13 g
2
n
–
NH with M(acac) . The amine functionalized silica/starch
2
Cu(acac) , 0.15 g Pd(acac) , 0.19 g Ru(acac) , 0.12 g
2 2 3
n
support can stabilize the metal acetylacetonate complexes
effectively and prevent the aggregation of metal particles.
Co(acac) and 0.17 g Mn(acac) ] in dry toluene (50 mL) was
3 3
refluxed at 120 °C for 12 h (Scheme 1). The ASS-M(acac)n
1
23

Schiff Condensation of 3-Aminopropyl-Silica/Starch Composite
1821
OH OH
OH
OH
OH
OH OH
O
O
Cl Cl
SiO
2
Starch
SOCl2
HO
HO
OH
OH
OH
Cl
Cl
Cl
CHCl /Et N
Cl
Cl
3
3
SiO2
SiO2
O
O
reflux
reflux
O
O
n
OHOH
O
Cl Cl
OH OH
n
O
Starch
OH
O
MeO
MeO Si
MeO
o
NH2 Dry toluene, 120 C
reflux, 15 h
OHOH
O
O
SiO
2
O
Si
NH2
O
OH OH
O
M(acac) 3
Dry toluene, 120 C
reflux, 15 h
o
O
O
O
O
O
O
O
SiO2
n
O
Si
N
O
O
O
O
O
OH
n
O
M
OH
OH
O
O
O
O
Si
NH
2
O
O
O
O
n
O
O
O
OH
M(acac)
2
Dry toluene, 120 C
reflux, 15 h
n
O
OH
OH
o
Si
N
O
O
O
M
O
O
OH
OH
O
O
O
ASS-M(acac)3
O
SiO2
O
Si
N
O
O
M= Co, Mn, Ru
O
M
O
O
O
O
O
O
O
n
O
OH
n
O
OH
OH
Si
O
N
O
O
M
O
O
ASS-M(acac)2
M= Co, Cu, Pd
Scheme 1 General procedure for the synthesis of amine functionalized silica/starch-M(acac)
n
was filtered off, washed with hot toluene (50 mL) till the
and ASS-Cu(acac) (0.2 g, 3.5 mol % Cu) in a round-
2
washings were colorless and dried in a hot air oven at 110 °C
bottom flask (25 mL), water (5 mL) was added and
the reaction mixture was stirred at 100 °C for an
appropriate time (Scheme 2). After completion of the
reaction (monitored by TLC), the reaction mixture
was diluted with ethyl acetate and filtered. The resi-
due was treated with hot ethyl acetate (3 9 10 mL)
and the organic layer was washed with water
(100 mL) and dried over anhyd. Na SO . Finally, the
for 5 h. In order to remove any physisorbed M(acac) , the
n
catalysts were conditioned by refluxing for a total of 9 h in
xylene at 130 °C (2 9 2 h), ethanol at 78 °C (2 9 2 h) and
acetonitrile at 80 °C (2 9 2 h). Finally, ASS-M(acac) were
n
dried in a hot air oven at 110 °C for 4 h.
2
.3 General Procedure for the Thioetherification
of Aryl Halides
2
4
product was obtained after removal of the solvent
under reduced pressure followed by purification using
flash chromatography on silica gel (EtOAc-Petroleum
ether).
To a mixture of aryl halide (1 mmol), benzyl bromide
1.1 mmol), K CO3 (2 mmol), thiourea (1.2 mmol)
(
2
123

1
822
R. K. Sodhi et al.
X
+
S
S
Br
ASS-Cu(acac)2
R
H N
NH2
+
R
2
K CO , H O
2
3
2
o
1
00 C
Scheme 2 ASS-Cu(acac)
Scheme 3 ASS-Cu(acac)
2
2
catalyzed one-pot thioetherification of arylhalides using thiourea as the source of sulfur
H
catalyzed one-pot synthesis of
H-indazoles via consecutive
C–N and N–N bond formations
NH2
2
O
R1
ASS-Cu(acac)2
R1
N
+
NaN
+
3
Br
o
DMSO, 100 C
N
2
.4 General Procedure for the Synthesis of 2H-
Indazoles Under Thermal Conditions
potential for chelation with other functional groups/reagents/
metal ions. Starch is composed of two polymers: amylose, a
linear polymer and amylopectin which is highly branched
polysacchride. Highly branched structure of amylopectin can
supply more hydroxy groups that can better interact and
facilitates the grafting of chemical species to achieve differ-
ent surface properties (surface functionalization). It is rather
surprising that despite the abundant functional groups present
in biopolymers, the successful method for functionalization
has not been reported yet. The functionalization of silica/
starch composite with 3-aminoproplytrimethoxy silane
A mixture of 2-bromobenzaldehyde (1.5 mmol), primary amine
1.8 mmol), sodium azide (2 mmol) and ASS-Cu(acac) (0.2 g,
(
2
3
.5 mol% Cu) in DMSO (5 mL) was stirred at 100 °C for an
appropriate time (Scheme 3). After completion of the reaction,
the reaction mixture was diluted with ethyl acetate and filtered.
The residue was washed with hot ethyl acetate (3 9 10 mL) and
the combined organic extracts were washed with water
(100 mL) and dried over anhyd. Na SO . Finally, the product
2 4
was obtained after removal of the solvent under reduced pressure
followed by purification in a flash chromatography on silica gel
introduces free –NH groups onto the surface of the silica/
2
starch composite. The functionalized silica/starch composite
containing surface –NH could bind with the M(acac)
(
EtOAc-Petroleum ether). The catalyst was washed with EtOAc
3 9 5 mL) followed by double distilled water (3 9 10 mL)
and dried at 100 °C for 2 h, and reused for subsequent reactions.
2
n
(
strongly, as a result, the possibility of the leaching of the
active metal from the catalyst surface would be slow during
the liquid phase reactions. The general procedure for the
2
.5 General Procedure for the Synthesis of 2H-
synthesis of amine functionalized silica/starch-M(acac) is
n
Indazoles Under Microwave Irradiation
represented in Scheme 1. It involves the preparation of amine
functionalized silica/starch substrate followed by Schiff
condensation of the surface –NH with M(acac) . The metal
A mixture of 2-bromobenzaldehyde (1.5 mmol), primary amine
1.8 mmol), sodium azide (2 mmol) and ASS-Cu(acac) (0.2 g,
2
n
(
is a lewis acid which is being an electron acceptor while the
ligand being lewis base can donate the electron pair to central
metal. The bond between metal and ligand is a lewis acid–
base interaction. First, activated silica was converted to silica
chloride using thionyl chloride [46], followed by reaction
with starch in chloroform and triethylamine to obtain the
silica/starch substrate. M(acac)n (where M=Co, Cu, Pd,
n = 2; Co, Mn, Ru, n = 3) was refluxed with amine func-
tionalized silica/starch substrate in dry toluene followed by
simple filtration and drying in the oven at 110 °C. All the six
heterogeneous catalysts were characterized by FTIR, TGA
and AAS analysis. In addition to this, the most active catalyst
was further characterized by scanning electron microscopy
(SEM) and transmission electron microscopy (TEM) [48].
Among the various supported metal acetylacetonates tested,
2
3
.5 mol% Cu) in DMSO (5 mL) was placed in a closed vial
(
10 mL) and irradiated in a microwave synthesizer at 100 °Cfor
an appropriate time (monitored by TLC). The product was
obtained after the similar work-up as given in Sect. 2.4.
1
The structure of the products were confirmed by H and
1
3
C NMR, mass spectral data and comparison with authentic
samples obtained commercially or prepared according to the
literature methods [43–45].
3
Results and Discussion
3
.1 Characterization of Covalently Anchored M(acac)n
onto Amine Functionalized Silica/Starch
Composite [ASS-M(acac)n]
ASS-Cu(acac) was found to be the most active.
2
The FTIR of silica/starch composite showed bands in
-
the range 3700–3200 cm which were assigned to surface
1
Covalently bonded silica/starch composite contains several
free hydroxy groups on their backbone which have the
-
1
–OH groups, and 1101 and 804 cm due to m (Si–O–Si)
as
1
23

Schiff Condensation of 3-Aminopropyl-Silica/Starch Composite
1823
Fig. 1 FT-IR of ASS-Cu(acac)
2
Table 1 Characterization of covalently anchored M(acac)
analysis
n
onto amine functionalized silica/starch composite by FTIR, AAS and thermal
a
b
c o
TGA ( C)
Entry
Catalyst
FTIR
AAS analysis
(Metal wt%)
-1
)
(
C=N, tmax in cm
Loss of residual solvent
Loss of organic functionality
1
2
3
4
5
6
a
ASS-Cu(acac)
ASS-Co(acac)
2
2
1646
1658
1642
1637
1650
1620
1.1
1
100
90
90
95
90
70
250–300
280–300
250–290
230–300
250–280
220–300
ASS-Pd(acac)
2
1.8
0.9
1.1
1.7
ASS-Mn(acac)
3
ASS-Co(acac)
ASS-Ru(acac)
3
3
FTIR was recorded on Perkin-Elmer FTIR spectrophotometer using KBr discs
b
AAS analysis was carried on GBC Avanta-M atomic absorption spectrometer. The catalyst was stirred in dil. HCl for 10 h and then subjected
to AAS analysis
c
Thermal analysis was carried out on Linsesis STA PT-1000 make thermal analyzer with heating rate of 10 °C/min
Fig. 2 Thermo-gravimetric
analysis of ASS-Cu(acac)
2
123

1
824
R. K. Sodhi et al.
Table 2 Elemental analysis of ASS composite and ASS-Cu(acac)
2
Elemental analysis
Component
Element %
a
CHNS (ASS composite)
Carbon
13.82
2.40
1.55
1.1
Hydrogen
Nitrogen
Copper
b
AAS [ASS-Cu(acac)
2
]
a
CHN elemental analysis was carried out on vario MICRO Cube
CHNS analyzer
b
AAS analysis was carried on GBC Avanta-M atomic absorption
spectrometer
Fig. 4 TEM images of covalently anchored Cu(acac)
functionalized silica/starch composite [ASS-Cu(acac)
2
onto amine
2
]
partial coverage of the silica/starch surface with amino-
propyl groups. The two broad bands at 3434
-
1
and 1630 cm
can be ascribed to the N–H stretching
vibration and NH2 bending mode of free NH2 group,
respectively. The presence of the anchored propyl group
was confirmed by C–H stretching vibrations that appeared
Fig. 3 SEM images of covalently anchored Cu(acac)
functionalized silica/starch composite [ASS-Cu(acac)
2
onto amine
2
]
-
1
and m (Si–O–Si), respectively. After functionalization of
at 2924 and 2851 cm
.
After complexation with
s
silica/starch substrate with 3-aminopropyltrimetoxysilane,
M(acac) , the –CH stretching band got shifted to
n
2
-
2932 cm . ASS-Cu(acac) exhibits well defined bands at
1
some slight changes were observed in the spectrum due to
2
1
23

Schiff Condensation of 3-Aminopropyl-Silica/Starch Composite
1825
Table 3 Comparison of catalytic activities of different covalently
(Fig. 3a). The SEM images of ASS-Cu(acac) showed a
2
n
anchored M(acac) complexes onto aminefunctionalized silica/starch
very slight roughening of the surface of the catalyst which
composite for one- pot thioetherification and synthesis of 2H-
indazoles
may possibly be due to the interaction of Cu(acac) with
2
the surface of the support material (Fig. 3b). The TEM
images provided a direct observation of the morphology
and distribution of copper onto the surface of amine
functionalized silica/starch composite. Particle size was
derived from TEM micrographs, which indicated that the
individual particles have spherical shape with an average
diameter of 2–2.5 nm (Fig. 4). The regular arrangement of
the pores can be clearly observed. In the TEM images, the
black colored spots could be attributed to the presence of
grafted Cu-sites formed due to the coordination of Cu(II)
with the surface of the support. No bulk aggregation of the
metal occurred indicating that copper is dispersed evenly
onto the surface of support material with near spherical
morphology.
a
b
Entry
Catalyst
Thioethers
2H-indazoles
c
c
Time
h)
Yield
(%)
Time
(h)
Yield
(%)
(
1
2
3
4
5
6
a
ASS-Cu(acac)
ASS-Co(acac)
2
2
1.25
92
75
75
70
70
60
6
6
6
6
6
6
85
50
55
40
50
20
2
2
2
2
2
ASS-Pd(acac)
2
ASS-Mn(acac)
3
ASS-Co(acac)
ASS-Ru(acac)
3
3
Reaction conditions: bromobenzene (1 mmol), benzyl bromide
1.1 mmol), thiourea (1.2 mmol), K CO (2 mmol), ASS-M(acac)
n
(
(
(
2
3
1.1 wt% M) [M=Cu, Ru, Pd, Co, Mn; n = 2 or 3] at 100 °C in water
5 mL)
b
Reaction conditions: 2-bromobenzaldehyde (1.5 mmol), aniline
1.8 mmol), sodium azide (2 mmol), ASS-M(acac) (1.1 wt% M)
(
[
c
n
3.2 Catalytic Testing for the One-Pot
M=Cu, Ru, Pd, Co, Mn; n = 2 or 3] at 100 8C in DMSO (5 mL)
Thioetherification and Synthesis of 2H-Indazoles
Isolated yield
Initially, to select the most appropriate heterogeneous
metal acetylacetonate catalyst, the thioetherification in case
of test substrates (4-bromobenzaldehyde, benzyl bromide
and thiourea) was carried out using different amine func-
-
646 and 1410 cm due to C=O and/or C=N and C=C
1
1
respectively. This is a strong evidence for anchoring of
tionalized silica/starch-M(acac)n [ASS-M(acac) (M=Co,
n
Cu(acac) onto the surface of amine functionalized silica/
2
Cu, Mn, Pd and Ru, n = 2 or 3, 3.5 mol% metal] at 100 °C
in water. The screening of various catalysts allowed us to
starch composite through Schiff condensation of NH and
2
C=O (Fig. 1). The characteristic C=N bands for supported
metal acetylacetonates are presented in Table 1. The sta-
bility of the catalysts was determined by thermogravimetric
analysis. The TGA was recorded by heating the sample at
select ASS-Cu(acac) as the most effective catalyst for
2
one-pot thioetherification of aryl halides with thiourea and
benzyl bromide in water (Table 3).
In order to optimize the protocol and to understand the
influence of different variables on this reaction, several
components were studied to increase its efficiency. Choice
of a solvent plays an important role in multi-component
reactions. To choose the appropriate solvent for this reac-
tion, we carried out the test reaction in a variety of protic
and aprotic solvents, and water was found to be the best
solvent in terms of reaction time and yield. K CO showed
-
1
the rate of 10 °C min . The TGA curve of ASS-Cu(acac)2
showed an initial weight loss up to 100 °C, which was
attributed to the loss of residual solvent and water trapped
onto the surface. The major weight loss from 250 to 300 °C
was due to the decomposition of starch and chemisorbed
material i.e. aminopropyl group from the silica/starch
substrate (Fig. 2). Thus, the catalyst is stable up to 250 °C
and it is safe to carry out the reaction at 100 °C under
heterogeneous conditions. The major weight losses of all
the six catalysts are presented in Table 1.
2
3
the best performance, furnishing the desired product in
quantitative yield. However, in the absence of a base no
product formation takes place. Temperature is considered
as a major factor that affects the rate of a reaction. The
reaction with the test substrate was tried at room temper-
ature but unfortunately reaction did not go to completion.
With the increase in temperature to 50 or 70 °C, the rate of
the reaction was very slow. However, the reaction at
100 °C provided the highest yield with maximum selec-
tivity. Using the optimized conditions, the present reaction
was further extended to a broader range of substituted aryl
halides in order to evaluate the scope of the method
(Scheme 2, Table 4) and found that the reaction works well
for both electron-donating and electron-withdrawing
The loading of aminopropyl group onto silica/starch
composite was determined from C, H, N elemental analysis
and the loading of Cu was determined by AAS analysis
(
Table 2). ASS-Cu(acac) contained 1.1 wt% copper per g
2
of the catalyst which is very close to the theoretical value
of 1.5 wt%. The AAS of all the six catalysts is presented in
Table 1. In order to understand the surface morphology and
to assess the surface dispersion of metal onto amine
functionalized silica/starch composite, the systematic study
on SEM analysis was done. SEM images showed wooly
cloud like clusters with somewhat spherical morphology
123

1
826
R. K. Sodhi et al.
Table 4 ASS-Cu(acac) catalyzed thioetherification of different aryl halides using thiourea under aqueous medium at 100 °C
2
Entry
Aryl halide
Product
Time (h)
Yield (%)a
S
S
S
S
S
1.25
92
87
1
2
Br
2
1
.50
H
2
N
Cl
Cl
Br
Cl
2
H N
.50
2
82
88
87
90
3
4
5
6
7
8
2
HOH C
2
HOH C
H
3
COC
COC
H
3
COC
COC
1
H
3
H
3
S
S
S
2
3
.50
NC
Br
Br
Cl
NC
.50
2
90
85
OHC
OHC
OHC
OHC
Reaction conditions: aryl halide (1 mmol), benzyl bromide (1.1 mmol), thiourea (1.2 mmol), K
Cu) at 100 °C in water (5 mL)
2
CO
3
2
(2 mmol), ASS-Cu(acac) (0.2 g, 1.1 wt%
a
Isolated yield
groups. In general, the reaction is clean and high yielding.
In order to select the optimum amount of catalyst, reaction
in case of test substrates was carried out with varying
amount of catalysts and found that 3.5 mol% Cu gave the
best results in terms of reaction time and yield. With this
protocol, the preparation of structurally diverse thioethers
becomes more practical and easier than available protocols
in which thiols are directly used for the preparation of aryl
alkyl thioethers.
The reaction proceeds by the generation of S-alkyliso-
thiouronium salt A which was hydrolyzed in the reaction
mixture to produce a thiolate moiety and urea. Urea was
hydrolyzed to produce carbon dioxide gas and ammonia as
the final products of the hydrolysis reaction. The generated
thiolate ion react by the oxidative addition reaction with
Cu(II) to form intermediate B, which undergoes reaction
with aryl halide to form arylorganocopper C. Intermediate
C undergoes reductive elimination resulting in the
1
23

Schiff Condensation of 3-Aminopropyl-Silica/Starch Composite
1827
Fig. 5 Proposed mechanism for
ASS-Cu(acac) catalyzed
thioetherification of aryl halides
with thiourea and benzyl
bromide
H N
2
S
Br
2
S
+
A
BrH N
2
H N
2
NH2
OH
S
OH
NH2
NH2
Cu
PhX
S
O
H N
2
B
O
NH2
NH2
S
H N
2
OH/H O
Ph
X
2
Cu
S
Cu(II)
CO + 2NH OH
2
4
C
S
Ph
D
formation of thioether D with the regeneration of the cat-
alyst (Fig. 5).
functionalized silica/starch composite, silica supported
Cu(acac) , starch supported Cu(acac) , Cu(acac) and
2
2
2
Initial attempts to optimize the reaction conditions for the
synthesis of 2H-indazoles (Scheme 3), aniline and 2-bro-
mobenzaldehyde were chosen as the test substrates and the
reaction was carried out in the presence of different amine
functionalized silica/starch-M(acac)n catalysts (Table 3).
without using catalyst (for thioethers, 4-bromobenzalde-
hyde, benzyl bromide and thiourea; for 2H-indazoles,
aniline, 2-bromobenzaldehyde). Starch by itself could not
give the satisfactory results. Starch supported Cu(acac)2
suffered with several disadvantages such as hydrophilic
nature of starch and poor mechanical stability especially
ASS-Cu(acac) was again turned out to be the best catalyst
2
for the synthesis of 2H-indazoles. After identifying the most
efficient catalyst (Table 3), we further screened different
solvents in order to enhance the reaction rate. Among the
various solvents examined (acetonitrile, water, ethanol,
DMSO), the reaction proceeded well in DMSO, which was
found to be the most appropriate solvent. Furthermore,
reaction of most of the substrates with several aromatic
amines bearing electron-donating as well as electron-with-
drawing groups were performed smoothly and the corre-
sponding 2H-indazoles were obtained in good yields
under aqueous medium. Silica supported Cu(acac) was
2
found to be active under the optimized conditions and
provided good yield in reasonable time (Fig. 6). The
results are summarized in Table 6, which indicated that
Cu(acac) under homogeneous conditions gave the best
2
results, but since they were miscible in the reaction
medium so it was a painstaking process to remove and
retain it for reuse. The use of heterogeneous systems
would be more advantageous as catalyst recovery is
easier, process is more efficient and moreover, the catalyst
could be recycled for several runs. The biopolymer con-
taining hybrid material of silica has drawn attention
owing to their promising properties and creative alterna-
tives to design new materials for academic research and
innovative industrial applications. Thus, we have selected
ASS-Cu(acac)2 as the heterogeneous catalyst for both
these reactions. Recyclability and operational stability of
(
Table 5).
For the synthesis of 2H-indazoles, reactions have also
been carried out under microwave irradiation (Table 5).
The comparison between conventional and microwave-
assisted method showed that, the microwave protocol
predate the conventional method by significantly reducing
reaction time with remarkable improvements in efficiency,
yields and energy consumption.
ASS-Cu(acac) was tested in case of entry 1 (Table 1,
2
In order to find out the role of ASS-Cu(acac) as the
2
thioether; Table 2, 2H-indazole) (Fig. 5). It was found
heterogeneous catalyst, the test reaction was carried out in
that ASS-Cu(acac) could be recycled for four consecu-
2
the presence of silica/starch composite, amine
tive runs without loss of significant activity.
123

1
828
R. K. Sodhi et al.
Table 5 ASS-Cu(acac)
DMSO
2
catalyzed one-pot synthesis of 2H-indazoles from 2-bromo-benzaldehydes, various primary amines and sodium azide in
Time (h)
Yield (%)a
Entry
Product
Δ
MW
Δ
MW
6
0.5
85
75
85
N
1
2
N
8
0.75
82
N
CH
3
N
1
2
1
75
73
80
82
N
Br
3
4
N
1
4
1.15
N
Cl
N
1
0
0.75
1.20
70
80
75
N
OMe
5
6
N
1
3
70
N
NO
2
N
2
Reaction conditions: 2-bromobenzaldehyde (1.5 mmol), primary amine (1.8 mmol), sodium azide (2 mmol), ASS-Cu(acac) (0.2 g, 1.1 wt% Cu)
at 100 °C in DMSO (5 mL)
a
Isolated yield
3
3
.2.1 Spectral Data of Compounds
3.2.1.3 4-(Benzylthio)phenyl Methanol (Table 3, entry
1
3)
Brown oil, [49]. H NMR (CDCl ): d 3.69 (s, 2H, -CH ),
3
2
1
4.53 (s, 2H, –CH OH), 7.35–7.45 (m, 9H, Harom). C NMR
3
.2.1.1 Benzyl Phenyl Sulfide (Table 3, entry 1) White
1
2
solid, M.p./Lit. M.p. 42–43/40–43 °C [47]. H NMR
(CDCl ): d 35.69, 64.45, 122.24, 123.47, 125.57, 127.04,
3
(
1
CDCl ): d 3.70 (s, 2H, –CH ), 7.35–7.48 (m, 10H, Harom).
127.49, 129.49, 137.47, 138.24, 139.57. MS (ESI): 233
3
2
3
C NMR (CDCl ): d 35.71, 127.08, 127.53, 128.50,
(M ? 2).
3
?
29.13, 139.70. MS (ESI): 200 (M) .
1
3
.2.1.4 Benzyl 4-Acetylphenyl Sulfide (Table 3, entry
3
.2.1.2 Benzyl4-Aminophenyl Sulfide (Table 3, entry 2) Brown
1
4) White soild, M.p./Lit. M.p. 112-114/113–115 °C [50].
oil, [48]. H NMR (CDCl ): d 3.45 (s, 2H, –CH ), 4.47 (s, 2H,
3
2
1
H NMR (CDCl ): d 2.15 (s, 3H, –COCH ), 3.59 (s, 2H, –
3
3
–
7
1
1
NH ), 6.36–6.43 (t, 2H, H
2
), 6.92–6.96 (m, 2H, Harom),
arom
1
3
CH
13
2
), 7.22–7.39 (m, 5H, Harom), 7.50–7.62 (m, 4H, Harom).
.06–7.20 (m, 5H, Harom). C NMR (CDCl ): d 43.10,
3
C NMR (CDCl ): d 35.55, 57.22, 115.13, 127.33, 127.94,
3
16.02, 122.71, 126.45, 127.54, 128.9, 129.31, 138.02,
?
45.22. MS (ESI): 217 (M) .
?
.
128.59, 128.99, 138.11, 152.33. MS (ESI): 241 (M)
1
23

Schiff Condensation of 3-Aminopropyl-Silica/Starch Composite
1829
Recyclability
Table 6 Comparison of activity of ASS-Cu(acac) with silica/starch
2
composite, amine functionalized silica/starch composite and homo-
geneous Cu(acac)
1
00
2
for the synthesis of thioethers and 2H-indazoles
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
a
b
Entry Catalyst
Thioether
2H-Indazole
Time Yield Time Yield
c
c
(h)
(%)
(h)
(%)
d
d
1
2
3
No catalyst
4
4
4
NR
5
10
10
10
NR
Silica/starch composite
Traces
5
Amine functionalized
silica/starch composite
15
1
2
3
4
4
5
6
7
a
SiO
Starch-Cu(acac)
Cu(acac)
ASS-Cu(acac)
2
-Cu(acac)
2
4
75
60
90
92
6
6
6
6
70
50
80
85
Number of runs
2
4
Thioether
2H-indazole
2
0.8
1.25
2
Fig. 6 Recyclibility of ASS-Cu(acac)
2
: Reaction conditions- bromo-
benzene (1 mmol), benzyl bromide (1.1 mmol), thiourea (1.2 mmol),
CO (2 mmol), ASS-Cu(acac)
(0.2 g, 1.1 wt % Cu) at 100 °C in
water (5 mL) [for thioethers]; 2-bromobenzaldehyde (1.5 mmol),
Aniline (1.8 mmol), sodium azide (2 mmol), ASS-Cu(acac) (0.2 g,
Reaction conditions: bromobenzene (1 mmol), benzyl bromide
(1.1 mmol), thiourea (1.2 mmol), K CO (2 mmol), and catalyst
(0.2 g for entries 1-3; 0.002 g, 3.5 mol% Cu for entry 4; and 0.2 g,
K
2
3
2
2
3
2
3.5 mol% Cu for entry 5) at 100 °C in water (5 mL)
1
.1 wt % Cu) at 100 °C in DMSO (5 mL) [for 2H-indazoles]
b
Reaction conditions: 2-bromobenzaldehyde (1.5 mmol), aniline
1.8 mmol), sodium azide (2 mmol), and catalyst (0.2 g for entries
–3; 0.002 g; 3.5 mol% Cu for entry 4; and 0.2 g, 3.5 mol % Cu for
(
1
entry 5) at 100 °C in DMSO (5 mL)
Isolated yield
3
.2.1.5 Benzyl 4-Cyanophenyl Sulfide (Table 3, entry
1
c
6
)
White solid, M.p./Lit. M.p. 83–84/84–85 °C [51]. H
d
NR No reaction
NMR (CDCl ): d 3.62 (s, 2H, –CH ), 7.26–7.32 (m, 4H,
Harom), 7.33–7.37 (m, 5H, Harom). C NMR (CDCl ): d
3
2
1
3
3
3
8.73, 109.03, 115.64, 127.46, 128.83, 129.03, 137.38,
?
38.15. MS (ESI): 226 (M) .
1
3.2.1.9 2-(4-Methoxyphenyl)-2H-Indazole (Table 4, entry
3
)
White solid, M.p./Lit. M.p. 146–147/146–148 °C [53].
1
H NMR (CDCl ): d 3.22 (s, 3H, –OCH ), 7.11–7.13 (d,
3
3
3
7
.2.1.6 Benzyl 4-Formylphenyl Sulfide (Table 3, entry
1
2
H, Harom), 7.15–7.17 (d, 2H, Harom), 7.32–7.36 (t, 2H,
)
White solid, M.p./Lit. M.p. 70–71/70–72 °C [52]. H
Harom), 7.72–7.74 (d, 1H, Harom), 7.79–7.81 (d, 1H, Harom),
NMR (CDCl ): d 3.61 (s, 2H, –CH ), 7.26-7.35 (m, 5H,
Harom), 7.69–7.72 (m, 4H, Harom), 9.17 (s, 1H, –CHO).
3
2
13
.52 (s, 1H, Harom). C NMR (CDCl ): d 55.20, 113.12,
14.20, 120.34, 122.3, 126.69, 130.12, 149.66, 155.33. MS
?
ESI): 225 (M ? 1) .
8
1
1
3
3
C
NMR (CDCl ): d 35.58, 127.42, 128.66, 130.14, 137.37,
1
3
(
?
38.14, 142.18, 171.18. MS (ESI): 227 (M) .
3
.2.1.7 2-Phenyl-2H-Indazole (Table 4, entry 1) White
1
3.2.1.10 2-(4-Chlorophenyl)-2H-indazole (Table 4, entry
solid, M.p./Lit. M.p. 81–82/81–82 °C [53]. H NMR
4) White solid, M.p./Lit. M.p. 130–131/130–132 °C [53].
1
(
CDCl ): d 7.12–7.14 (t, 1H, Harom), 7.33–7.34 (t, 1H,
H NMR (CDCl ): d 7.12–7.14 (d, 2H, Harom), 7.14–7.16
3
3
Harom), 7.41–7.45 (t, 1H, Harom), 7.54–7.57 (t, 2H, Harom),
(d, 2H, Harom), 7.33–7.35 (t, 2H, Harom), 7.35–7.37 (t, 2H,
1
3
7
7
.73–7.75 (d, 1H, Harom), 7.80–7.82 (d, 1H, Harom),
Harom), 8.43 (s, 1H, Harom). C NMR (CDCl ): d 113.5,
3
1
.92–7.94 (d, 2H, Harom), 8.4 (s, 1H, Harom). C NMR
3
120, 121.7, 125, 126, 130, 131, 138, 150. MS (ESI): 229
?
(M) , 230 (M ? 1).
(
(
CDCl ): d 117, 122, 126.8, 127.9, 129.6, 140.5, 149.8. MS
3
?
ESI): 195 (M ? 1) .
3.2.1.11 2-(4-Bromophenyl)-2H-indazole (Table 4, entry
3
.2.1.8 2-(4-Methyl)-2H-Indazole
(Table 4,
entry
5) Yellow solid, M.p./Lit. M.p. 140–142/141–143 °C
[54]. H NMR (CDCl ): d 7.13–7.16 (t, 1H, Harom),
3
1
2
)
White solid, M.p./Lit. M.p. 100–102/101–103 °C [53].
1
H NMR (CDCl ): d 2.45 (s, 1H, -CH ), 7.11–7.15 (t, 1H,
7.35–7.37 (t, 1H, Harom), 7.67–7.69 (d, 2H, Harom),
3
3
Harom), 7.34–7.36 (m, 3H, Harom), 7.72–7.74 (d, 1H, Harom),
7.71–7.74 (d, 2H, Harom), 7.78–7.80 (d, 1H, Harom),
13
7.82–7.84 (d, 1H, Harom), 8.42 (s, 1H, Harom). C NMR
1
.79–7.81 (m, 3H, Harom), 8.4 (s,1H, Harom). C NMR
3
7
(
CDCl ): d 21.01, 113.5, 120.8, 125.5, 126.6, 130, 137.9,
(CDCl
3
): d 117, 120, 122, 123, 127, 132.6, 139.5, 149.9.
3
?
38.2, 149.6. MS (ESI): 209 (M ? 1) .
?
MS (ESI): 273 (M ? 1) , 275 (M ? 2).
1
123

1
830
R. K. Sodhi et al.
3
6
.2.1.12 2-(4-Nitrophenyl)-2H-indazole (Table 4, entry
Yellow solid, M.p./Lit. M.p. 219–220/218–220 °C
10. Budarin VL, Clark JH, Luque R, Macquarrie DJ, White RJ (2008)
Green Chem 10:382–387
)
1
1. Gronnow MJ, Luque R, Macquarriea DJ, Lee JHMS, Jo NJ
2002) J Sol-Gel Sci Technol 24:175–180
1
[
55]. H NMR (CDCl ): d 7.07–7.08 (t, 1H, Harom),
3
(
7
7
8
.30–7.33 (t, 1H, Harom), 7.64-7.66 (d, 1H, Harom),
12. Zhou J, Zhang SW, Qiao XG, Li XQ, Wu L (2006) J Polym Sci
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13. Yu YY, Chen CY, Chen WC (2003) Polymer 44:593–601
.70–7.72 (d, 1H, Harom), 8.06–8.09 (m, 2H, Harom),
1
.33–8.36 (m, 2H, Harom), 8.4 (s, 1H, Harom). C NMR
3
1
4. Carrot G, Diamanti S, Manuszak M, Charleux B, Vairon JP
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15. Bokobza L, Gamaud G, Mark JE (2002) Chem Mater 14:162–167
(
CDCl ): d 128.5, 131, 131.8, 135, 135.4, 137, 141, 161.7,
3
(
?
64, 169. MS (ESI): 240 (M ? 1) .
1
1
1
1
6. Chen YC, Zhou SX, Yang HH, Wu LM (2006) J Sol-Gel Sci
Technol 37:39–47
7. Rana VK, Park SS, Parambadath S, Kim MJ, Kim SH, Mishra S,
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8. Zou H, Wu S, Shen J (2008) Chem Rev 108:3893–3957
4
Conclusions
In conclusion, we have reported the synthesis of a series of
novel metal acetylacetonates covalently anchored onto
amine functionalized silica/starch composite and its cata-
lytic activity was studied for the one-pot thioetherification
of aryl halides with benzyl bromide using thiourea in
water, and for the one-pot three component synthesis of
19. Nezhad AK, Panahi F (2012) J Organomet Chem 717:141–146
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4. Cheng SW, Tseng MC, Lii KH, Lee CR, Shyu SG (2011) Chem
Commun 47:5599–5601
2
H-indazoles by consecutive C–N and N–N bond forma-
tions. This procedure is free from foul-smelling thiols and
work-up becomes easy, practical and eco-compatible,
diminishing environmental concerns. Compared with lit-
erature protocols, our approach offers very mild reaction
conditions and affords the corresponding products in
moderate to excellent yields. The catalyst was found to be
highly active and could be recycled for four consecutive
runs without significant loss of activity.
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Acknowledgements We thank the Head, Regional Sophisticated
Instrumentation Centre, Nagpur University, Nagpur for AAS analysis;
Head, SAIF, Punjab University Chandigarh for FT-IR and SEM and
Head, SAIF, IIT Bombay for TEM studies, Director IIIM Jammu for
CHNS elemental analysis. We gratefully acknowledge Department of
Science and Technology, Government of India for NMR spectrometer
5
2:2694–2707
3
3
3. Wu C, Fang Y, Larock RC, Shi F (2010) Org Lett 12:2234–2237
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LR, Li J, Addo MF, Croll D, Eckardt AJ, Smith CE, Li Q,
Cheung WM, Conway BR, Emanuel S, Demarest KT, Gordon
PA, Damiano BP, Maryanoff BE (2005) J Med Chem 48:
3
(
Bruker Avance III, 400 MHz) under PURSE program to the Uni-
versity of Jammu, Department of Chemistry, University of Jammu for
spectral and TGA analysis. We also thank UGC, New Delhi for
financial support (SAP, DRS I and Major research Project, F-41-281/
1
725–1728
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012 (SR).
3
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