Catalytic metallodendrimers grafted on mesoporous polymethacrylate beads for the regioselective synthesis of β-amino alcohols under solvent-free conditions

Article abstract of DOI:10.1039/c5ra04903b

A new series of dendritic structures was grafted on epoxy activated mesoporous polymethacrylate beads (Sepabeads EB-EP-400). Grafting with the dendritic structures was followed by loading of metal termini to the chelating groups to form metallodendrimer-g

Full text of DOI:10.1039/c5ra04903b

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PAPER
Catalytic metallodendrimers grafted on
mesoporous polymethacrylate beads for the
regioselective synthesis of b-amino alcohols under
solvent-free conditions†
Cite this: RSC Adv., 2015, 5, 42526
*
Richa Tiwari, Sachdeo H. Daware and Sandeep B. Kale
A new series of dendritic structures was grafted on epoxy activated mesoporous polymethacrylate beads
(Sepabeads EB-EP-400). Grafting with the dendritic structures was followed by loading of metal termini
to the chelating groups to form metallodendrimer-grafted catalysts. The catalysts were characterized by
UV, FTIR, SEM and elemental analysis. Further, a selected catalyst was used to afford b-amino alcohols in
a regioselective manner through nucleophilic opening of an oxirane ring with various aromatic amines
under solvent-free, mild reaction conditions. The reactions with the developed catalyst at ambient
temperature afforded the corresponding b-amino alcohols in high yields (85–99.5%) with excellent
regioselectivity. It was found that the developed metallodendrimer-based catalyst is efficient and
recyclable without compromising on activity, selectivity and productivity (4 kg LÀ1 hÀ1).
Received 19th March 2015
Accepted 21st April 2015
DOI: 10.1039/c5ra04903b
www.rsc.org/advances
sluggish amine nucleophiles, several catalysts such as metal
halides,7,8 metal alkoxide,9 transition metal salts,10,11 ionic
liquids,12 and Amberlyst-15,13 and various promoters such as
1. Introduction
Currently, green chemistry has become a major driving force for
the development of environmentally friendly processes and
catalyst materials for the organic synthesis of various pharma-
ceuticals, ne chemicals and intermediates. The possibility of
performing multi-component reactions under solvent-free
conditions, and to enhance the reaction efficiency with 3e’s,
i.e. an ecological, environmental and economical point of view,
using a solid recyclable catalyst has received special attention.
This approach of green chemistry is currently investigated for
the simplied synthesis of b-amino alcohols in various
laboratories.
Amino alcohols are of importance as versatile intermediates
in the synthesis of a wide range of biologically active, natural
and synthetic products including pharmaceuticals, synthetic
amino acids, pesticides, polymers and chiral auxillaries.1–5 The
most common method used for the synthesis of amino alcohols
involves the oxirane ring opening of an epoxide with an excess
of amine at high temperatures.6 However, under these condi-
tions, sensitive epoxides and amines undergo undesirable side
reactions showing poor regioselectivity and reduced applica-
bility to temperature sensitive reactants like poorly nucleophilic
amines or sterically crowded amines/epoxides. In order to
overcome such problems in the ring opening of epoxides with
BiCl3,14 CoCl2,15 ZrCl4,16 ZnCl2,17 TaCl5,18 Sm(OTf)3,19
Ti(OiPr)4,9,20 Sc(OTf)3,21 Al(OTf)3,22 B(C6F5)3,23 aluminosiilicate,24
NaY zeolite,25 and Fe-MCM-41,26 have been reported in the
literature to perform ring opening reactions. The use of
microwave irradiation27 and Y(NO3)3$6H2O28 as a catalyst under
solvent-free conditions have also been reported. The amino
alcohol synthesis using a variety of air sensitive catalysts29 and
even without a catalyst30 with aliphatic amines at room
temperature has also been reported. Many of these existing
methods employ corrosive and expensive catalysts and
hazardous organic solvents at high pressures and temperatures,
and still offer moderate yields and poor selectivities with long
reaction times. Few catalysts are even moisture and air sensitive
and non-recyclable. Sometimes, the reaction yields an unde-
sired product through the rearrangement of epoxides to allyl
alcohols in a basic medium and through polymerization in an
acidic medium, leading to reduced yields and purity of the
desired products. Hence, there is a growing need for simple,
economic and efficient catalysts which are more active and
selective towards aromatic amines, and have reasonable recy-
clability. To surmount the limitations, we report an easy to
handle, solid and recyclable metallodendritic green catalyst
based on rigid mesoporous polymeric beads for the green and
efficient synthesis of b-amino alcohols at room temperature
under solvent-free conditions and without the use of any acid or
base.
DBT-ICT-Centre for Energy Biosciences, Institute of Chemical Technology, NP Marg,
Matunga (E), Mumbai 400019, Maharashtra, India. E-mail: sb.kale@ictmumbai.
edu.in; sanykale@gmail.com; Fax: +91-22-33611020; Tel: +91-22-33612313
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c5ra04903b
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Metallodendrimers are gaining signicant interest in the Tris (i.e. 2-amino-2-hydroxymethyl-propane-1,3-diol) was
eld of organometallic catalysis and a wide variety of them have coupled to the matrix under alkaline conditions.40 The Tris-G0-
been prepared and applied in certain applications. Two specic Sepabeads were then epoxy activated using epichlorohydrin (G1-
advantages of catalysts based on dendritic ligands graed on Sepabeads). To these epoxy activated G1-Sepabeads, Tris was
rigid, porous polymeric solid beads are: (i) an enhanced kinetic again covalently coupled to increase its branching followed by a
performance and better conversions when compared to those of second epoxy activation using epichlorohydrin to obtain the G2-
monomeric complexes, owing to their large surface area with Sepabeads. Finally, iminodiacetic acid (IDA) was immobilized
large ligand sites, and (ii) stable macromolecular structures, on the terminal epoxy groups of the G0, G1 and G2 series of
making them suitable for isolation using simple ltration, thus activated Sepabeads followed by the loading of the termini with
enabling catalyst recovery and recycling.31 Reactions which are metal ions to form the M2+-metallodendrimer-graed G0, G1
catalyzed using metallodendrimers include polymerizations,31 and G2 series of the mesoporous Sepabead catalysts (ESI†).
Suzuki–Miyaura reactions,32 oxidations,33,34 Sonogashira reac-
tions,35 hydroformylations and C–C coupling metathesis,36–38
epoxide ring openings39 etc.
2.2. Catalyst characterization
Determination of the metal ion loading on the prepared series
In the present work, rigid, mesoporous polymethacrylate
of mesoporous Sepabeads graed with metallodendritic side
Sepabeads EB-EP-400 were graed with metallodendritic side
groups as catalysts, was carried out. 50 mL of each metal free
groups. The metallodendritic side groups loaded with a series of
catalyst was washed with 5 bead volumes (i.e. 250 mL) of
transition metals encouraged us to explore the beads as an
deionised water before loading the resin with the terminal
efficient, reusable and convenient promoter catalyst for the
metal ions. To each series of washed dendrimer-graed Sepa-
opening of the oxirane ring of epoxides with aromatic amines
beads, 10 bead volumes of a 0.5 M solution of either nickel(II)
for the synthesis of b-amino alcohols. Based on the design of the
sulphate heptahydrate, copper(II) sulphate pentahydrate,
metallodendrimer-graed polymethacrylate beads as an
cobalt(II) chloride hexahydrate or ferrous(II) sulphate was added
economical as well as environmentally friendly catalyst, the
for loading the Ni2+, Cu2+, Co2+ or Fe2+ ions. Binding was
green process for the aminolysis of epoxides under solvent-free
conditions is reported.
ꢀ
allowed for 12 h under mild shaking conditions at 25 C. The
concentrations of the different ions in the solution before and
aer the loading of metal ions were determined by the spec-
trophotometric method of Belew and Porath41 at their respective
lmax (ESI†). The amount of metal ions loaded on each series of
2. Experimental
All chemicals and reagents used in the study were of analytical
grade and used without further purication. Sepabeads EB-EP-
400 (G0-Sepabeads), rigid, mesoporous polymethrylate beads
with epoxy functionality, were obtained from Resindion SRL,
Italy, (Mitsubishi chemical Co., Japan). Amines, epoxides and
heptauorobutyric acid (used as an ion pairing agent) were
obtained from Sigma-Aldrich, India. Thin layer chromatog-
raphy (TLC) was performed on Merck aluminium sheets pre-
coated with silica gel 60-F254 to a thickness of 0.25 mm, and
the chromatograms obtained were evaluated under long range
ultraviolet light (254–264 nm). Merck silica gel (100–200 mesh)
was used for column chromatography. HPLC grade acetonitrile
and water were obtained from Merck, India, and were used for
recording mass spectra on an Agilent Technologies 6450 Triple
Quad mass spectrometer, and for determining the purity on an
Agilent Technologies 1200 series high performance liquid
chromatography (HPLC). FTIR spectra were recorded on a Shi-
madzu IR prestige-21 spectrophotometer. The surface
morphology was analyzed by scanning electron microscopy
(SEM) using a JSM-6380, and elemental analysis was performed
on a NCHS&O elemental analyzer (Thermo Scientic, USA).
dendrimer-graed Sepabeads was determined by a material
balance. The metallodendritic Sepabead catalyst thus prepared,
was again washed with 5 bead volumes of deionised water
before conditioning it for its actual use. The G0-Sepabeads, Tris
immobilized intermediates and epoxy activated intermediates
from the G1 and G2 series were also evaluated as controls for
metal binding determination.
The surface morphologies of the G0-Sepabeads, dendrimers
with IDA-graed Sepabeads and aer loading the termini with
metals were analyzed by SEM, and the percentage of CHNS and
oxygen was estimated using an elemental analyzer.
2.3. Typical procedure for the synthesis of b-amino alcohols
from epoxides
Synthesis of b-amino alcohols from epoxides was carried out in
a solvent (water, methanol, chloroform, dichloromethane,
toluene, tetrahydrofuran etc.) and under solvent free condi-
tions. To a mixture of epoxide (1 mmol) and aromatic amine
(1 mmol), the M2+-metallodendrimer-graed Sepabead catalyst
(4%) was added and the mixture was stirred at ambient
temperature. The progress of reaction was monitored on a TLC
plate using ethyl acetate–hexane (1 : 9) as the mobile phase till
complete consumption of the epoxide was achieved. The
complete disappearance of the epoxide was observed within
2.1. Preparation of metallodendrimer-graed rigid,
mesoporous polymethacrylate beads as catalysts
Metallodendrimer-graed mesoporous catalysts were prepared 0.5–3 h. The reaction mixture was separated by simple ltration.
using polymethacrylate-based epoxy activated mesoporous G0- The recovered catalyst was washed with 2 bead volumes of ethyl
Sepabeads. As per the protocol of Hermanson et al. (1992),40 acetate and reused. The crude reaction mixture was concen-
the G0-Sepabeads were initially washed with water, and then trated under reduced pressure to obtain the crude product. The
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purity of the crude products and conversion percentage of the media, and are recyclable. In the present work, an efficient and
starting material were determined by HPLC analysis. The crude versatile method for the regioselective synthesis of amino alco-
product was puried using preparative column chromatog- hols using M2+-metallodendrimer-graed Sepabeads as the cata-
raphy on silica gel using ethyl acetate–hexane (1 : 9) as the lyst is derived. Polymethacrylate-based rigid, mesoporous beads
mobile phase. All pure b-amino alcohols were then character- were used to gra a dendrimer with the ability to complex metal
ized using ATR-FTIR (IR-prestige, Shimadzu, Japan) and mass ions at the termini (Fig. 1d, representation of the metal termini).
spectrometry (ESI+).
3.1. Catalyst and product (b-amino alcohol) characterization
2.4. Product characterization
Mesoporous Sepabeads EB-EP-400 obtained from Resindion
SRL, Italy, (Mitsubishi Chemical Corporation, Japan) had an
The synthesized b-amino alcohols were analyzed on an Eclipse
Plus C18 reverse phase analytical column (250 Â 4.6 mm,
particle size 5 mm, Agilent Technologies). An isocratic mobile
phase of acetonitrile and HFBA (pH 3.5, 2% heptauorobutyric
acid in water) with a ratio of 30 : 70 (v/v) at a ow rate of 1 mL
minÀ1 was used. 3 mL of each sample (crude, puried product
etc.) was injected and analyzed for 30 min using a DAD detector
oxirane content of 42 mmol mLÀ1, a particle size of 50–150 mm,
and an average pore size of 40–50 nm. A wavelength scan (200 to
800 nm) for each metal ion solution was carried out and the
absorbance maxima (lmax) were determined. lmax for the solu-
tions of Ni2+, Cu2+, Co2+ and Fe2+ ions were found to be 390, 760,
510, and 293 nm, respectively. The metal binding dendrimer
was graed onto the surface of the Sepabeads to obtain the G0,
G1 and G2 series of activated media, followed by the metal
loading resulting in the respective series of metallodendrimer-
graed Sepabeads with either Ni2+, Cu2+, Co2+ or Fe2+ metal
termini; a representation of the Ni2+ loaded G0, G1 and G2
series of the metallodendritic structures on the surface of the
polymethacrylate beads is shown in Fig. 2. A difference in the
metal loading capacities was observed for each series of cata-
lysts (Table 1). The isolated yields of G0, G1 and G2 are 98.2%,
98.7 and 99.6% (w/w), respectively.
The ability to synthesize b-amino alcohols in the presence of
each metallodendrimer catalyst was studied using aniline as a
reference for the amine group and with epichlorohydrin under
solvent-free conditions. Among the four different metal ions
(Ni2+, Cu2+, Co2+ and Fe2+) tested, the Ni2+-G2-metallodendrimer
gave maximum catalytic activity with 97% yield in 0.5 h (Table 2,
entry 1). The Cu2+ catalyst gave 89% yield in 1.5 h, whereas the
Co2+ and Fe2+ catalysts gave 87% and 80% yield in 2 h,
ꢀ
(260 nm) and column oven at a temperature of 30 C.
Mass spectra of each puried product were recorded on a
6410 Triple Quad Mass spectrometry system (Agilent Technol-
ogies, USA) by direct injection of a 10 ppm concentrated sample
at a ow rate of 1 mL minÀ1 for 1.6 min. The mobile phase used
was composed of acetonitrile and HFBA (pH 3.5, 2% hepta-
uorobutyric acid in water) with a ratio of 80 : 20 (v/v). The mass
spectrometer was operated in ESI positive mode with a scan
range of 50–300 m/z (scan type – MS2Scan, scan – 500, frag-
mentor at 135 V). The source conditions were: capillary at
4500 V, pressure limit 0–400 bar, gas temperature at 350 ꢀC, gas
ow – 8 L minÀ1, and nebulizer at 45 psi. ATR (attenuated total
reection) corrected spectra were also recorded using an IR
prestige-21 (Shimadzu, Japan). ATR-FTIR was used to detect the
functional groups of the amino alcohols at wave numbers from
4000 to 400 cmÀ1
.
2.5. Reusability and regeneration of the M2+
-
metallodendrimer-graed Sepabead catalyst
Reusability of the catalyst was examined by conducting the
reaction for up to ten consecutive cycles using the M2+-G2 series
metallodendrimer-graed Sepabead catalyst for the regiose-
lective synthesis of b-amino alcohols. A series of experiments
was carried out using the aforementioned reaction conditions
to investigate the consistency and efficiency of the catalytic
activity and conversion percentage. Aer completion of each
cycle, the catalyst was recovered by simple ltration, and
washed with ethyl acetate, methanol, and distilled water to
remove the traces of the product, reactant and impurities. The
recovered catalyst was dried at 50–60 ꢀC for 2 h and was reused
in the next cycle. Aer 5 cycles, the catalyst was regenerated
using a 0.5 M solution of the metal salt as described above, and
was reused in the process.
3. Results and discussion
Fig. 1 SEM images of the (a) native Sepabeads EB-EP-400, (b) Sepa-
beads EB-EP-400 after grafting the dendritic side groups with terminal
IDA, (c) Sepabeads EB-EP-400 after grafting the dendritic side groups
with the metal termini loaded on IDA. (d) Representation of metal
termini in a designed M2+-metallodendrimer-grafted Sepabead cata-
Most recently, solid supported dendrimers with terminal metal
complex ligands have gained considerable interest as catalysts in
numerous organic reactions because these catalysts are more
active as well as stable in aqueous, aqueous–organic and organic lyst (Ni2+-G2-metallodendrimer Sepabeads EB-EP-400 catalyst).
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Fig. 2 Representation of Ni2+ loaded G0, G1, and G2 series of metallodendritic structures on surface of polymethacrylate-based Sepabeads EB-
EP-400.
Table
1
Metal loading capacities of M2+*-G2 metallodendrimer-
metallodendrimer-graed Sepabeads showed the presence of
nitrogen (0.8%) and oxygen (13.2%) due to the use of Tris and
IDA during graing of the dendrimer on the surface. ATR-FTIR
spectra recorded on IR prestige-21 (Shimadzu, Japan) in the
transmission mode at a resolution of 4 cmÀ1 with 40 scans
(ESI†) showed a characteristic peak for the carbonyl (C]O)
group in the glycidyl methacrylate ester at 1728 cmÀ1. The
vibrational band at 961 cmÀ1, associated with the asymmetric
epoxy ring bending, disappeared aer metal loading onto
terminal IDA. Upon incorporation of the Ni2+ moieties to the
ligands in the G0, G1, and G2 series of the Sepabeads with IDA
groups, the spectra of the compounds exhibited a distinct shi
based Sepabeads catalysis
Loading capacity (mM mLÀ1
(G0) (G1)
55.28 148.00
)
Metal ion
Sr. no.
M2+
*
(G2)
358.36
1
2
3
4
Ni2+
Cu2+
Co2+
Fe2+
351.16
59.55
1120.15
159.87
3986.29
457.00
441.69
1387.21
4828.00
respectively (Table 2, entries 2–4). Based on these results, the
Ni2+-G2-metallodendrimer-graed Sepabead catalyst was
chosen for all further studies.
of nsym(C]O) to lower frequencies 1712, 1705, and 1693 cmÀ1
,
respectively. The position of the NH absorption in the spectra of
the polymeric complexes remained particularly unaltered as it
occurred in the OH frequency region. The occurrence of lattice
water in the complex and the IDA ligand showed strong and
As the resulting dendritic catalyst is highly crosslinked and
insoluble in any solvent, characterization was limited to SEM,
elemental analysis and ATR-FTIR. The surface morphology of
the G0-Sepabeads with and without graing of metal-
lodendrimer was analyzed by SEM (Fig. 1). Without graing of
metallodendrimer, the mesoporous Sepabeads EB-EP-400
showed a smooth surface, whereas a rough surface was
observed aer graing of metallodendrimer onto it. The data of
CHNS and oxygen elemental analysis showed only carbon and
hydrogen in the case of the G0-Sepabeads, whereas the
broad OH frequency absorptions at 3200–3600 cmÀ1
.
Complexation of Ni2+ with the IDA ligands was conrmed by the
IR spectra of the G0, G1, and G2 dendrimers, in which the OH
frequency got shied to lower frequencies of 3387, 3371, and
3363 cmÀ1
, respectively. Thus, the change in surface
morphology, elemental data and ATR-FTIR gave clear indication
of the metallodendrimer being graed onto the Sepabeads EB-
EP-400 surface.
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Table 2 Effect of M2+*-G2 metallodendrimer-based Sepabead catalysis under solvent and solvent-free conditions for different amines with
epichlorohydrin under optimized reaction conditions (molar ratio 1 : 1)
Entry
Amine
M2+*-G2 Sepabeads EB-EP-400a
Solvent
Time (h)
Yieldb (%)
Effect of catalyst
1
2
3
4
5
Aniline
Aniline
Aniline
Aniline
Aniline
Ni2+-G2 Sepabeads EB-EP-400
Cu2+-G2 Sepabeads EB-EP-400
Co2+-G2 Sepabeads EB-EP-400
Fe2+-G2 Sepabeads EB-EP-400
No catalyst
Solvent-free
Solvent-free
Solvent-free
Solvent-free
Solvent-free
0.5
1.5
2.0
2.0
12.0
97
89
87
80
44
Effect of solvent
6
7
8
Aniline
Aniline
Aniline
Aniline
Aniline
Aniline
p-Aminophenol
p-Aminophenol
p-Aminophenol
p-Aminophenol
p-Aminophenol
p-Aminophenol
m-Toluidine
m-Toluidine
m-Toluidine
m-Toluidine
m-Toluidine
m-Toluidine
Aniline
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
Ni2+-G2 Sepabeads EB-EP-400
No catalyst
Water
Methanol
3.0
5.0
6.5
6.0
6.0
5.0
3.0
5.0
6.5
6.0
6.0
5.0
3.0
5.0
6.5
6.0
6.0
5.0
12.0
38
35
23
30
32
30
40
33
23
28
35
35
45
40
29
35
33
37
39
Chloroform
Dichloromethane
Toluene
Tetrahydrofuran
Water
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
Methanol
Chloroform
Dichloromethane
Toluene
Tetrahydrofuran
Water
Methanol
Chloroform
Dichloromethane
Toluene
Tetrahydrofuran
Water
a
b
M2+-divalent transition metals: Ni, Cu, Fe, and Co. The yield refers to isolated product aer column purication.
Aer characterization, the catalyst was employed in the aniline was used as a model system and it was found that
synthesis of b-amino alcohols under solvent and solvent-free Sepabeads graed with the G2 generation of the metal-
conditions (Table 2). The progress of the reaction was deter- lodendrimer are more active and gave higher yields than those
mined by HPLC analysis and the functional groups of the amino with the G0 and G1 generations. The effect of the G0, G1 and G2
alcohols were identied by ATR-FTIR. The b-amino alcohols generations could be attributed to the concentration of metal
were analyzed by mass spectrometry as shown in Table 3, entry ions, where the catalytic activity of the G2 series was found to be
1a: (ESI-MS) m/z: 152.2 (M + 1); entry 2a: (ESI-MS(+)) m/z: 166.2, 6 to 7 times higher than that of the G0 series and 2.5 to 3 times
entry 7a: (ESI-MS(+)) m/z: 182.2 (M + 1), 240.3, entry 8a: (ESI-MS) better than that of the G1 series catalysts for the respective
m/z: 186.6 (M + 1), 188.2 (M + 2, Cl isotope); entry 9a: (ESI-MS) m/ metal ions. This demonstrates the effect of metal ion content on
z: 200.2 (M + 1), 202.2 (M + 2, Cl isotope), 182.2 (M À 18, loss of the ring opening of epoxides with amines. We also prepared the
H2O molecule); entry 10a: (ESI-MS) m/z: 202.2 (M + 1), 204.2 (M + G3 series of the Ni2+-metallodendrimer-graed Sepabead cata-
2, Cl isotope); entry 12a: (ESI-MS) m/z: 200.3 (M + 1), 202.3 (M + lyst using a similar protocol mentioned earlier, and used it in
2, Cl isotope); entry 14a: (ESI-MS) m/z: 216.2 (M + 1), 218.6 (M + the reaction. With the G3 series of the metallodendrimer cata-
2, Cl isotope); entry 16b: (ESI-MS) m/z: 228.3 (M + 1), 134.2; entry lysts loaded with different metal termini, we obtained a reduced
21b: (ESI-MS) m/z: 244.3 (M + 1).
reaction rate, conversion and yield with all metals (data not
shown), which could be attributed to the drawback of dendritic
catalysis commonly observed with the increase in dendrimer
generation, known as the negative dendritic effect.35 Therefore,
the G2 series of the catalyst was selected for further studies. The
high catalytic activity of developed G2 catalyst can also be
attributed to the mesoporous nature of the beads with a high
surface area (550 m2 gÀ1), leading to superior mass transfer and
pore diffusion.42,43 It is relevant to highlight that the same
reaction when conducted without catalyst did not proceed to
any appreciable extent even aer 12 h where only 44% yield was
obtained (Table 2, entry 5).
3.2. Catalytic performance
To estimate the scope and applicability of the catalyst, epoxides
were reacted with different aromatic amines. The designed Ni2+
metallodendrimer catalyst was used for the ring opening of
epoxides with amines giving the corresponding b-amino alco-
hols (Scheme 1). The catalytic activity of the Ni2+ metal-
lodendrimer catalyst for the regioselective ring opening of
epoxides with amines under optimized reaction conditions, is
shown in Table 3. The ring opening of epichlorohydrin with
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Table 3 Ring opening of epoxides by the Ni2+-G2 metallodendrimer-based Sepabeads EB-EP-400 catalyst under solvent-free conditionsa
Time (h),
RT
Entry
1
Amine
Epoxide
b-Amino alcohol
Yieldb (%)
98.0
E factor
0.5
0.1363
2
3
4
5
6
1.5
2.0
2.0
2.0
1.0
95.0
93.0
96.0
94.0
98.0
0.0526
0.0752
0.0416
0.0638
0.0204
7
8
2.0
0.5
96.0
97.0
0.0416
0.0309
9
1.0
1.0
1.5
99.5
92.0
89.0
0.0050
0.0869
0.1235
10
11
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Table 3 (Contd.)
Time (h),
RT
Entry
12
Amine
Epoxide
b-Amino alcohol
Yieldb (%)
95.0
E factor
1.0
0.0526
13
14
15
1.0
1.0
2.0
99.0
94.0
85.0
0.0101
0.0638
0.1764
16
17
1.5
1.5
90.0
89.0
0.1111
0.1235
18
1.5
81.0
0.2345
19
20
1.5
1.0
85.0
91.0
0.1764
0.0989
21
1.0
83.0
0.2048
a
Epoxides (1 mmol) were treated with anilines (1 mmol) and the catalyst: Ni2+-G2 metallodendrimer Sepabeads EB-EP-400 (4%) (temperature: RT,
under solvent-free conditions, reaction time: 0.5 to 3 h). b Yields refer to isolated products aer column chromatography.
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the ring opening reactions of different epoxides with amines
having a different structure and charge, was evaluated (Table 3,
entries 1–21). Comparatively higher conversions were obtained
when epichlorohydrin instead of propylene oxide and styrene
oxide was reacted with amines. Although epichlorohydrin has
many reactive positions and can lead to some other side prod-
ucts, we did not observe any side products in the reaction (by
mass spectrometry analysis). The reaction of aniline with
styrene oxide gave the maximum yield (91%) for a single isomer
showing superior regioselectivity of the present catalyst (Table
3, entry 20). The aliphatic epoxides predominantly gave the type
‘a’ isomer whereas the aromatic (styrene) oxide predominantly
gave the type ‘b’ isomer. This could be attributed to the charge/
electronic effects favoring the attack at a less substituted carbon
atom of aliphatic epoxides (Table 3, entries 1–14) and the
possible localization of the positive charge of the oxygen on a
highly substituted benzylic carbon in styrene oxide (Table 3,
entries 15–21). The metallodendrimer catalyst has also shown
strong tolerance to electron donating/withdrawing groups on
aniline leading to the predominant formation of a single type of
isomer (Table 3, entries 1–21), demonstrating its regioselective
capability. This study further reveals that the type of epoxide is a
major determining factor for the type of isomer formed in the
aminolysis reaction. In the present work, both aliphatic and
aromatic epoxides gave high yields with superior regio- and
chemoselectivity.
Scheme 1 Reaction scheme for the ring opening reaction of epoxides
with amines using the designed catalyst.
3.2.1 Effect of solvent. The solvent effect on the catalytic
activity of the Ni2+-metallodendrimer catalyst was also studied,
and the results of the aminolysis of epoxides are summarized in
Table 2. It was observed that the catalytic rate was higher with
divalent transition metals (e.g. Ni2+
) ligated onto the
metallodendrimer-graed Sepabeads EB-EP-400 catalyst under
solvent-free conditions (Table 2, entries 1–4) than in the pres-
ence of aqueous and organic solvents (Table 2, entries 6–23).
From Table 2 (entries 6–23), it can be seen that the polarity of
the solvent has a signicant effect on the catalytic activity of the
Ni2+-metallodendrimer catalyst. Among the different solvents
studied, polar solvents, i.e. water (Table 2, entries 6, 12 and 18),
gave a better catalytic activity and yield than the comparatively
non-polar or intermediate polar solvents tested. The catalytic
activity was substantially reduced with non-polar or interme-
diate polarity solvents for the ring opening reaction of epoxides
with aniline (Table 2, entries 7–11), p-aminophenol (Table 2,
entries 13–17) and m-toluidine (Table 2, entries 19–23). When
aniline was used in the presence of water without a catalyst, the
reaction aer 12 h gave only 39% yield (Table 2, entry 24).
Hence, this effect could be due to the hydrophobic solvent
getting adsorbed on the solid metallodendrimer catalyst,
making a lower number of sites accessible for the reaction. On
the other hand, with water and under solvent-free conditions, a
large number or all sites remain accessible for the reactant
molecules to yield a high conversion in less time. In particular,
when the reaction was carried out using the Ni2+-metal-
lodendrimer catalyst, aniline was completely consumed (99%
conversion) and 97% yield of the desired product (Table 3, entry
8) was obtained aer column chromatography. The maximum
yield (i.e. 99.5%) was obtained under solvent-free conditions
with the designed regioselective Ni2+-metallodendrimer catalyst
(Table 3, entry 9).
3.2.3 Catalyst recycling and catalysis in a packed column.
Catalyst recycling studies were conducted, and the performance
in each cycle was determined. It was found that 92% conversion
was obtained even aer the 10th cycle. Thus, the catalyst was
found to be reusable and studies indicated that metal ions did
not leach from the catalyst during the course of its use, making
the process techno-economically viable and environmentally
friendly.
3.2.2 Effect of catalyst loading and substrate. The effect of
catalyst loading (1 to 6.5 mol%) on the performance in the
reaction was also studied, where the increase in initial catalyst
concentration up to 4 mol% showed an increase in yield of the
corresponding amino alcohols (ESI†). The increase in the
amount of catalyst from 4 to 6.5 mol% did not show an incre-
mental effect on the yield of the desired amino alcohols (ESI†).
Further, applicability of the Ni2+-metallodendrimer catalyst for
Fig. 3 Proposed mechanism of the ring opening of epoxides with the
dendritic catalyst.
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Fig. 4 Packed bed system for the continuous catalytic reaction using the Ni2+-G2-metallodendrimer Sepabeads EB-EP-400 catalyst.
The proposed mechanism for the ring opening of the oxirane Sepabeads catalyst offers many advantages of a solid catalyst
ring with different amines in the presence of the Ni2+
-
over other catalysts from the viewpoint of green chemistry such
metallodendrimer-based Sepabeads EB-EP-400 catalyst is as solvent-free conditions, simplication of the work-up,
shown in Fig. 3. To explore the feasibility of using the designed formation of cleaner products with no side products,
catalyst continuously and to prove the industrial viability, we improved reaction rates, low catalytic amounts, catalyst recy-
developed a system consisting of a packed bed of catalyst cling and an easy isolation procedure, making it a better alter-
coupled with metal ion trapping and product purication native to existing catalysts. Furthermore, under the stated
modules as shown in Fig. 4. The metal ion trapping module was conditions, a catalytic column was also operated continuously
a column (1/100th of the volume of the catalytic column) packed for 72 h which showed high productivity (4 kg LÀ1 hÀ1). During
with the chelating resin Diaion CR11 (Mitsubishi Chemical this operation, no signicant reduction in conversion and
Corporation, Japan). This was used to avoid any possibility of productivity was observed which proves the industrial feasibility
passage of metal ions into the product. The purication module of the catalyst for the synthesis of b-amino alcohols.
consisted of silica gel operating under the conditions described
earlier. The catalytic column was operated continuously with a
1 : 1 molar ratio of the reactants (Table 3, entry 1). It was found
Acknowledgements
that, under the column mode, the catalyst required about 20
min of residence time to achieve >99.5% conversion of the
reactants into the corresponding b-amino alcohol. Recently, few
reports on polymer catalysts appeared to describe the ring
opening of epoxides at high temperatures with long reaction
times and in the presence of solvent44,45 as well as under non-
catalyzed reaction conditions.46 Comparison of the designed
Ni2+-metallodendrimer-based Sepabeads EB-EP-400 catalyst
with the few catalysts reported in the literature for the synthesis
of b-amino alcohols showed much superior catalytic activity,
and higher yields (97–99% yield) in signicantly less time (0.5 to
1.0 h) for our catalyst as compared to a recent report where a
nano Fe3O4 catalyst47 is used for the synthesis of b-amino
alcohols (ESI†).
We are very thankful for nancial support from Department of
Biotechnology (DBT) and University Grant Commission, New
Delhi, India.
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