Poly(hydroxamic acid) functionalized copper catalyzed C-N bond formation reactions

Article abstract of DOI:10.1039/c6ra08155j

Highly active poly(hydroxamic acid) functionalized copper catalysts were synthesized by the surface modification of khaya cellulose through graft copolymerization and subsequent hydroximation processes. The prepared catalysts were well characterized by FTIR, FESEM, HRTEM, ICP-AES, UV-vis and XPS analyses. The supported catalysts effectively promoted C-N bond formation reactions and provided excellent yields of the corresponding products under mild reaction conditions. The catalysts were easy to recover from the reaction mixture and were reused several times without any significant loss of their catalytic activity.

Full text of DOI:10.1039/c6ra08155j

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Poly(hydroxamic acid) Functionalized Copper Catalyzed C-N Bond
Formation Reactions
Md. Shaharul Islama, Bablu Hira Mandalab, Tapan Kumar Biswasac, Md. Lutfor Rahman*d, S. S. Rashida, Suat-
Hian Tana and Shaheen M. Sarkar*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Highly active poly(hydroxamic acid) functionalized copper catalysts were synthesized by the surface modification of khaya
cellulose through graft copolymerization and subsequent hydroximation processes. The prepared catalysts were well
characterized by FTIR, FESEM, HRTEM, ICP-AES, UV-vis and XPS analyses. The supported catalysts effectively promoted C-N
bond formation reactions and provided excellent yields of the corresponding products under mild reaction conditions. The
catalysts were easy to recover from the reaction mixture and were reused several times without any significant loss of
their catalytic activity.
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Michael addition MOF-99 [20], silica sulfuric acid [21],
Amberlyst-15 [22], cellulose-Cu(0) [23], polystyrene-AlCl3 [24],
KF doped natural zeolite [25], MCM-41 immobilized
Introduction
The addition reaction so-called Click [1] and Aza-Michael [2]
reactions are important C-N bond formation reactions have a
wide range application in the modern scientific communities
[3]. Traditionally, different copper complex sources have been
used for these reactions such as for Click reaction; Cu(II)/Cu(0)
comproportionation [4], mixed Cu/Cu-oxide nanoparticles [5],
in-situ reduction of Cu(II) to Cu(I) salts [6], for Michael
reaction; AlCl3 [7], PtCl4·5H2O [8], InCl3/TMSCl [9], Bi(NO)3 [10],
boric acid [11], bases [12]. However, these homogeneous
metal catalyzed reactions have several limitations like side
products, a high cost of metal complexes, harsh conditions,
long reaction times, metal leaching out into the reaction
mixture, difficult to recover the catalyst and require large
excesses of reagents or catalysts. Therefore, the use of
heterogeneous catalysts for organic synthesis is rapidly
growing over homogeneous catalytic systems because of their
several advantages such as high stability and tolerant to harsh
reaction conditions, reusability of the catalyst, environmental
friendliness and easy to purify of the products [13]. Thus,
heterogeneous metal catalysts have been utilized for the Click
and Michael addition reactions. For instance, Zeolites [14],
polymers [15], non-magnetic and magnetic supported Cu(I)
[16], silica [17], TiO2-nanotube [18], cellulose supported Cu(0)
[19] have been used effectively for Click reaction; whereas for
heteropoly acids [26], amine-functionalized silica supported
Co(acac)2 [27] proved good catalytic activity. Nevertheless,
from green technology aspects, there is still a high demand to
explore more efficient catalyst for chemical transformation
reactions. Nowadays, scientists are continuing their effort to
investigate low-cost environmental friendly and sustainable
processes using renewable resources. In this perspective,
natural biopolymers (cellulose) could be considered most
acceptable material because it has some promising merits like
large abundance in nature, low density, bio-renewability,
universal availability, low-cost and interesting mechanical
properties compared to the glass fibers [28]. Therefore,
natural cellulose would be the perfect candidate to consider as
a solid support for catalysts [29]. In addition, cellulose
backbone can be chemically modified and suitable metals
coordinating groups can be effectively introduced [30].
Currently, biopolymers like cellulose [31], starch [32] alginate
[33], gelatin [34], and chitosan [35] derivatives have been used
as supports for catalytic applications with acceptable catalytic
performance along with some drawbacks. Eventually, it is
particularly envisaged to unfold a more general, simple and
convenient catalytic process which could be applicable to
various substrates of different nature under pleasant and
environment-friendly reaction conditions. Keeping this view, in
this report we used copper anchored onto poly(hydroxamic
acid) functionalized khaya cellulose as efficient heterogeneous
catalysts for C-N bond formation via Click reaction [Cu(I)] of
organic azide and terminal alkyne, and chemoselective Aza-
Michael addition [Cu(0)] of aliphatic amines with α,β-
unsaturated compounds. The cellulose supported copper
catalysts were found highly active as well as chemoselective in
the C-N bond formation reactions. The catalysts were easy to
a.Faculty of Industrial Sciences and Technology, University Malaysia Pahang,
Gambang 26300, Kuantan, Malaysia
b.Department of Chemistry, Jessore University of Science and Technology, Jessore
7408, Bangladesh
c. Department of Chemistry, University of Rajshahi, Rajshahi 6205, Bangladesh
d.Faculty of Science and Natural Resources, University Malaysia Sabah,
Kotakinabalu 88400, Sabah, Malaysia
†Electronic Supplementary Informaꢀon (ESI) available: [IR and UV spectra of the
catalyst and all NMR data of the products are available]. See
DOI: 10.1039/x0xx00000x
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recover and reused without significant loss of its catalytic cellulose suspension and stirring was continued for another 4 h
activity.
under nitrogen atmosphere. The mixture was cooled at room
temperature when colorless cellulose supported poly(methyl
acrylate) was precipitated out and the obtained precipitates were
collected by glass filtration. The precipitates were washed several
times with aqueous methanol (methanol: water = 4:1) and dried at
50 °C to get a constant weight [36].
Experimental
General information
All manipulations were done under atmospheric conditions if
otherwise noted. Reagents and solvents were obtained from
commercial suppliers and used without further purification. Water Synthesis of the poly(hydroxamic acid) ligand 2
was deionized with a Millipore system as a Milli-Q grade.
The hydroxylamine solution was prepared by dissolving 12 g of
CuSO4·5H2O was purchased from Aldrich Chemical Industries, Ltd.
1H NMR (500 MHz), 13C NMR (125 MHz) spectra were measured
with a BRUKER-500 spectrometer, Central laboratory, University
Malaysia Pahang. The 1H NMR chemical shifts were reported
relative to tetra methylsilane (TMS, 0.00 ppm). The 13C NMR
chemical shifts were reported relative to CDCl3 (77.0 ppm).
Inductively coupled plasma atomic emission spectrometry (ICP-AES)
was performed on a Shimadzu ICPS-8100 equipment by the central
laboratory, University Malaysia Pahang. FTIR spectra were
measured with a Perkin Elmer (670) spectrometer equipped with an
ATR device (ZnSe crystal), FIST, University Malaysia Pahang. XPS
spectra were measured with a Scanning X-ray Microprobe PHI
Quantera II, MIMOS, Kuala Lumpur, Malaysia. FE-SEM was
measured with JSM-7800F, Central laboratory, University Malaysia
Pahang. TEM was measured with HT-7700, Hi-Tech Instruments
SDN BHD, Puchong, Malaysia. TLC analysis was performed on Merck
silica gel 60 F 254. Column chromatography was carried out on silica
gel (Wakogel C-200).
hydroxylamine hydrochloride (NH2OH·HCl) in 300 mL of aqueous
methanol (methanol: water = 4:1). An aqueous solution of NaOH
(50%) was added at cold condition into the hydroxylamine solution
and the resulting NaCl precipitates were removed by filtration. The
pH of the reaction was adjusted to pH 11 by control addition of
NaOH solution. Then poly(methyl acrylate) grafted khaya cellulose 1
(5 g) was placed into a two-neck round bottom flask fixed with a
stirrer, condenser and thermostat water bath. The prepared
hydroxylamine solution was then added into the flask and the
reaction was heated at 70 °C for 6 h. The chelating polymeric ligand
was separated from hydroxylamine solution by filtration and
washed with aqueous methanol. The ligand was treated with 200
mL of 0.1 M HCl (in methanol), filtered and washed several times
with methanol and dried at 50 °C to get a constant weight [36].
Preparation of the poly(hydroxamic acid) copper complex 3
A stirred suspension of 2 (2 g) in 50 mL water was added into an
aqueous solution of CuSO4·5H2O (492 mg, in 30 mL H2O) at room
temperature. The blue CuSO4 was immediately turned into green
color copper complex (Ø = 17.5 ± 2 nm, Fig. 1a) and the mixture was
stirred for 2 h at room temperature. The poly(hydroxamic acid)
copper complex 3 was filtered and washed several times with
excess amount of ammonium chloride, water, MeOH and dried at
60 °C for 2 h. The ICP-AES analysis showed that 0.5 mmol/g of
copper [36, 37] was adsorbed by the poly(hydroxamic acid) ligand.
Materials
Khaya fiber was obtained from local market at Kuantan, Pahang,
Malaysia and was cut into small pieces (∼0.5 cm). The raw fiber
(150 g) was boiled with 17% NaOH (800 mL) for 6 h and repeatedly
washed with distilled water. The resulting fiber was boiled with
glacial acetic acid (800 mL) for 1 h and washed with distilled water.
The dark color khaya cellulose was then bleached with hydrogen
peroxide (300 mL) and 7% NaOH (500 mL) respectively and washed
with distilled water (500 mL) for several times to obtain white color
cellulose and was dried at 50 °C before use. Methyl acrylate
Preparation of the poly(hydroxamic acid) Cu-nanoparticles
(CuN@PHA)
monomer purchased from Aldrich and it was passed through Poly(hydroxamic acid) copper complex 3 (500 mg) was dispersed in
column filled with chromatographic grade activated alumina to 50 mL deionized water and hydrazine hydrate (1 mL) was added
remove inhibitors. Other chemicals such as ceric ammonium nitrate into the reaction mixture. The resulting reaction mixture was stirred
(CAN) (Sigma-Aldrich), methanol (Merck), sulfuric acid (Lab Scan), at room temperature for 3 h. The dark brown color CuN@PHA (Ø =
metal salts and other analytical grade reagents were used without 3.2 ± 1 nm, Fig. 1c) material was collected by filtration, washed with
purification.
excess amount of water, methanol and dried under vacuum at 100
°C. The CuN@PHA was stored under nitrogen atmosphere [38].
Graft copolymerization 1
General procedure for Click reaction
The khaya cellulose (3 g) was dispersed into 300 mL distilled water.
The copolymerization reaction was carried out in 500 mL three-neck A 5-mL glass vessel was charged with 3 (1 mg, 0.05 mol%), alkyne (1
round bottom flask fixed with stirrer and condenser in thermostat mmol) and aromatic azide (1.1 mmol) in 5 mol% aqueous solution
water bath. Diluted sulfuric acid (1.1 mL, 50%) was added into the of sodium ascorbate (3 mL). The reaction mixture was stirred at 80
reaction mixture and it was heated at 55 °C. After 5 min, 1.1 g of °C for 3 h. The reaction mixture was diluted with EtOAc and the
CAN (10 mL aqueous solution) was added and the reaction mixture insoluble 3 was recovered by filtration. The organic layer was
was stirred under nitrogen atmosphere. After stirring for further 20 separated and the aqueous layer was extracted with EtOAc (3 x 2
min, 10 mL of methyl acrylate monomer was added into the mL). The combined organic layers were dried over MgSO4 and
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concentrated under reduced pressure to give the corresponding
triazoles. The crude product was purified by silica gel short column
chromatography (EtOAc /hexane).
General procedure for Michael addition reaction
In a typical experiment, a mixture of amine (10 mmol), α,β-
unsaturated Michael acceptor (11 mmol) and khaya cellulose
supported CuN@PHA (2 mg, 0.016 mol%) in 10 mL MeOH was
stirred at room temperature for 5 h. The reaction progress was
monitored by GC analysis. After completion of the reaction,
CuN@PHA was filtered, washed with MeOH (3 x 5 mL), dried, and
reused in the next run under the same reaction conditions. The
filtrate was concentrated to give the crude product, which was
purified by column chromatography (hexane/ethyl acetate) to give
the corresponding Michael addition products.
Results and discussion
The khaya fiber was successively boiled with 17% NaOH and glacial
acetic acid respectively. The resulting cellulose was then washed
with water and bleached with hydrogen peroxide. The obtained
white color cellulose was graft copolymerized with methyl acrylate
using ceric ammonium nitrate as an initiator to give cellulose
supported poly(methyl acrylate) 1 which was further treated with
hydroxylamine provided poly(hydroxamic acid) chelating ligand 2.
The poly(hydroxamic acid) functionalized khaya cellulose was then
treated with aqueous solution of CuSO4·5H2O at room temperature
Scheme 1. Preparation of the copper complex 3.
to give green color poly(hydroxamic acid) copper complex
3
(Scheme 1). The ICP-AES analysis revealed that 0.5 mmol/g of
copper was adsorbed with the poly(hydroxamic acid) ligand 2. The
copper complex 3 was then treated with hydrazine hydrate [38] to
give dark brown color CuN@PHA (Ø = 3.2 ± 1 nm).
It was found that the C=O band at 1742 cm-1 in 1 shifted to 1690
cm-1 which confirmed the successful production of hydroxamic acid
ligand onto the khaya cellulose. The C=O stretching band of
hydroxamic acid was found at 1738 cm-1 after its complexation
with Cu(II) [41]. New peaks at 1618, 1450 and 1162 cm-1 were
assigned for C=N and C-O stretching respectively. A peak at 615 cm-
FTIR analysis
The IR spectrum of fresh khaya cellulose showed adsorption bands
at 3430 and 2915 cm-1 which referred to O-H and C-H stretching,
respectively (Fig. 1, ESI). The band at 1655 cm-1 was due to the
bending mode of OH and a smaller peak at 1450 cm-1 was observed
for CH2 symmetric stretching [39]. The absorbance at 1385 and
1162 cm-1 originated from the O-H bending and C-O stretching,
respectively. The C-O-C pyranose ring skeletal vibration produced a
strong band at 1085 cm-1. A small sharp peak at 908 cm-1
corresponded to the glycosidic C1-H deformation with ring vibration
contribution and OH bending indicating α-glycosidic linkages
between glucose units in cellulose [39]. The IR spectrum of
poly(methyl acrylate) grafted cellulose 1 showed new absorption
bands at 1742, 1475, 1402 cm-1 due to C=O, scissoring and wagging
stretching of methyl group respectively [40]. The peak at 2980 and
2870 cm-1 represent C-H (sp3) stretching of methyl group. The
poly(hydroxamic acid) 2 showed new absorption bands at 1690 and
1651 cm-1 corresponding to the C=O stretching and N-H bending
modes. Additionally, a new broad band at 3185 cm-1 for N-H
stretching and 1410 cm-1 for OH bending were observed.
1
further confirmed the successful incorporation of copper with the
poly(hydroxamic acid) ligand 2 [41b].
FESEM, HRTEM, XPS and XRD analysis
The green color photo image showed copper complex 3 (Fig. 1a),
which was turned into light yellow (Fig. 1b) when treated with
sodium ascorbate in Click reaction and dark brown color (Fig. 1c),
CuN@PHA for Michael addition was obtained by the reduction of 3
with hydrazine hydrate.
(a)
(b)
(c)
Fig. 1 (a) Photo image of copper complex 3, (b) after reduction of 3 using
sodium ascorbate and (c) after reduction of 3 using hydrazine hydrate.
The FESEM micrograph of khaya cellulose showed stick like
morphology (Fig. 2a) whereas poly(methyl acrylate) grafted
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cellulose 1 showed distinguishable surface of wooden stick like
cellulosic structure having rough surface surrounding onto the stick
(Fig. 2b). The poly(hydroxamic acid) chelating ligand 2 exhibited
distinct spherical morphology (Fig. 2c) indicating the successful
hydroximation of 1. The SEM image of 3 displayed bigger spherical
morphology which revealed that ligand 2 was aggregated due to the
cross linkage between poly(hydroxamic acid) chelating ligands and
Cu(II) (Fig. 2d).
10
8
6
4
2
(a)
(c)
(e)
(b)
(d)
(f)
0
Diameter (nm)
Fig. 3 Size distribution of the CuN@PHA. The sizes were determined
for 100 nanoparticles selected randomly.
Cu2p3/2 934.5 eV
Cu2p1/2 953.2 eV
Cu Complex 3
Cu2p3/2 931.9 eV
Cu2p3/2 951.6 eV
CuN@PHA
960
955
950
945
940
935
930
925
Binding Energy (eV)
Fig. 4 XPS image of 3 and CuN@PHA.
2500
(111)
2000
1500
1000
500
0
Fig. 2 (a) SEM image of khaya cellulose, (b) SEM image of 1, (c) SEM image
of 2, and (d) SEM image of 3, (e) TEM image of copper complex 3, (f) TEM
images of CuN@PHA.
(200)
(220)
The TEM analysis of 3 showed in presence of Cu(II) onto the
cellulose surface (Fig. 2e) and the average particles size Ø = 17.5 ± 2
nm was measured. The TEM image of CuN@PHA demonstrated the
well dispersion of smaller size distribution (Fig. 3) of copper
nanoparticles (Ø = 3.2 ± 1 nm) onto the cellulose backbone (Fig. 2f).
The XPS spectrum of copper complex 3 and CuN@PHA were
showed (Fig. 4) a single Cu 2p3/2 peak at 934.5 and 931.9 eV which
are assigned for the binding energy of Cu(II) and Cu(0) respectively
[15c, 23, 38]. Additionally, an UV-vis spectrum of CuN@PHA
exhibited a single absorption at 694 nm (Fig. 2, ESI) that was
assigned for Cu-N coordination [15c]. The X-ray diffraction (XRD)
analysis of CuN@PHA confirmed the formation of metallic copper
nanoparticles in Bragg’s reflections at 2θ = 43.6, 50.5, and 74.5,
which can be indexed as the (111), (200), and (220) planes of
copper (Fig. 5) [42].
0
10
20
30
40
50
60
70
80
2-theta (deg)
Fig. 5 XRD pattern of CuN@PHA.
Copper catalyzed Click reaction
The khaya cellulose supported poly(amidoxime) copper complex 3
was used in the investigation for Click reaction of benzyl azide (5a)
and phenylacetylene (4a). The initial reaction was carried out using
1 mol% of 3 at 50 °C for 2 h in the presence of 5 mol% aqueous
solution of sodium ascorbate and was found to afford smoothly the
desired product, 6a in 92% yield (Table 1, entry 1). Whereas, 94%
and 90% yields were obtained when the same reactions were
performed using 0.5 and 0.1 mol% of 3 (entries 2, 3). We also
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accomplished the reaction by changing of catalyst loading,
temperature (entries 4-6) and eventually found that 0.05 mol% of 3
would be enough to promote this reaction efficiently (entry 4).
The 4-tolylacetylene (4b) react with benzyl azide (5a) and 1-azido-2-
phenylethane (5c) efficiently under similar reaction conditions to
provide the corresponding triazoles 6c and 6d in 93% and 91% yield
respectively. It should be noted that an aliphatic hex-5-yn-1-ol (4c),
readily reacted with a variety of benzyl and naphthyl azides to give
the corresponding triazoles 6e-g in 88-90% yields. The copper
complex 3 also promoted the reaction of cyclic alkynes bearing
tertiary alcohol 4d, acetal 4e and amine moieties 4f with benzyl
azide (5a) to give the corresponding products 6h-j in 89-91% yields.
Interestingly, our copper complex 3 did not affect the alcohol,
acetal, and amine groups. Thus, 3 can be used in the wide range of
substances.
Table 1. Optimization of the click reactiona
Entry
Cat (mol%)
Temp (◦C)
Time (h)
Yield (%)
1
2
3
4
5
6
1
50
50
50
80
90
90
2
4.5
7
92
94
90
96
89
92
0.5
CuN@PHA catalyzed Michael addition reaction
0.1
Being inspired by the successful application of 3 in Click reaction,
Michael addition reaction of amines and α,β-unsaturated
compounds was considered to find the catalytic versatility of the
prepared khaya cellulose supported Cu-catalyst. The addition
reaction between piperidine and butyl acrylate was taken as a
model reaction at room temperature to evaluate the optimum
condition for high catalytic performance of CuN@PHA. Table 3
present the results of the effect of catalyst dosages and reaction
time. The initial reaction was carried out using piperidine (7a) and
butyl acrylate (8a) in the presence of 0.16 mol% of (32 mg)
CuN@PHA which efficiently promoted the reaction to give the
corresponding addition product 9a in 94% yield within 1 h (Table 3,
entry 1). When 0.08 mol% of CuN@PHA was used, the reaction
time was increased as expected and it was raised to 2 h, (entry 2).
When the loading of CuN@PHA is further decreased (0.032 to 0.016
mol%), it took little longer time to complete the reaction (entries 3,
4). The catalyst loading was again decreased to 0.008 mol% (1 mg)
which also effectively forwarded the addition reaction (entry 5). It is
interesting to notice that the Michael addition reaction was also
promoted when 2 and 3 were used as a catalyst which provided
only 11 and 17% yield of 9a respectively (entries 6, 7).
0.05
0.01
0.05
3
6
2.5
aReactions were carried out using 1 mmol of phehylacetylene, 1.1
mmol of benzyl azide, catalytic amount of 3 in 5 mol% of aqueous
sodium ascorbate.
To explore the board applicability of 3 in the Click reaction with
various alkynes and azides were investigated under earlier settled
optimized reaction conditions and the results are summarized in
Table 2. When the cyclization of phenylacetylene (4a) and 4-
methylbenzyl azide (5b) was carried out with 3 in presence of 5
mol% sodium ascorbate at 80 °C for 3 h, 3 drove the reaction
smoothly to afford triazole 6b in 95% yield. The sodium ascorbate
reduced Cu(II) to Cu(I) and the color of 3 was changed from green
to yellow during the reaction progress (Fig. 1b).
Table 2. Click reaction of organic azides and alkynesa
Table 3. Optimization of Michael addition reactiona
Entry Catalyst
1
Mol%
Time (h)
TON
TOF (h-1) Yield (%)
0.16
0.08
1
2
4
5
6
5
5
587
1150
2812
5687
10875
-
587
575
703
1137
1812
-
94
92
90
91
87
11
17
2
CuN@PHA
3
0.032
0.016
0.008
(1 mg)
(1 mg)
4
5
6
2
3
7
-
-
aReactions were carried out using 10 mmol of piperidine, 11 mmol of
butyl acrylate in 10 mL MeOH at room temperature.
However, the TON and TOF calculation of the catalyst showed the
highest value when 0.008 mol% CuN@PHA was used (entry 5). As
far our knowledge, these are the highest TON and TOF obtained for
cellulose supported copper nanoparitcles catalyzed Michael
addition reaction.
aReactions were carried out using 1 mmol of alkyne, 1.1 mmol of
organic azide, 0.05 mol% of 3 in 5 mol% of aqueous sodium ascorbate at
80 °C for 3 h.
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Having the optimised conditions in hand, we investigated the wide activity was noticed after five cycles owing to the loss of CuN@PHA
applicability of CuN@PHA in Michael addition reaction (Table 4). during the filtration process. Only for Click reaction, ICP-AES
The five membered cyclic pyrolidine (7b) and sterically hinderd analysis showed that a trace amount of copper species (<0.13 mol
dibenzyl amine (7c) (10 mmol) underwent Michael addition reaction ppm of Cu) was washed out into the reaction mixture after five
with butyl acrylate (8a) (11 mmol) in the presence of 0.016 mol% (2 consecutive runs. Therefore, it can be rationally believed that our
mg) of CuN@PHA at room temperature in methanol to afford N- prepared catalysts can be recycled as well as reused repeatedly for
alkylated products 9b, 9c in 91% and 95% yield respectively. The large scale production with no significant loss of its catalytic activity.
addition reaction of dibenzyl amine (7c) and acrylonitrile (8b) was
efficiently forwarded to 9d in 92% yield. The CuN@PHA also fosterd
the Michael addition reaction of methyl acrylate (8c) with
piperidine (7a), dibutylamine (7d) and morpohline (7e) smoothly
affroded the corresponding products 9e-g in up to 95% yield. Thus,
it is observed that CuN@PHA effectively explored Michael addition
reaction with both open chain and cyclic secondary amines.
Click Reaction
95
96
94
95
95
93
91
87
88
83
Table 4. Michael addition reactiona
Michael Reaction
92
90
CO2Bu
CN
1
2
3
4
5
6
Ph
N
Ph
N
N
CO2Bu
91%
Ph
Ph
N
Fig. 6 Recycling of the copper complex 3 and CuN@PHA
9b:
9c:
9d:
92%
95%
CO2Me
O
N
Bu2N
Chemoselectivity test of Aza-Michael reaction
CO2Me
CO2Me
We further explored the chemo selectivity of CuN@PHA in N-
alkylation reaction, which is important in the synthetic applications.
For this, a mixture of 4-methylaniline and morpholine were exposed
with methyl acrylate (4 mol equiv) according to the Table 4. It is
very interesting to note that 4-methylaniline did not undergo the
reaction whereas only mono Michael adduct of morpholine 9g was
produced exclusively. This obviously indicated the chemo selectivity
of aliphatic amines versus aromatic amines towards the catalyst
CuN@PHA and this is due to the less reactivity of aromatic amines
compared to aliphatic amines.
9f: 93%
9g: 93%
9e:
95%
BuO2C
CO2Bu
NC
NC
CN
CN
NCH2CH2N
NCH2CH2N
BuO2C
CO2Bu
9h: 88%
9i: 87%
aReactions were carried out using 10 mmol of amine, 11 mmol of
Michael acceptor, 0.016 mol% of CuN@PHA in 10 mL MeOH at room
temperature for 5 h.
In addition, it is important to note that primary aliphatic amine,
ethylenediamine (7f) also efficiently took part in the Michael
addition reaction with 8a and 8b giving poly-alkylated products 9h
and 9i in 88% and 87% yield respectively. Recently, R K. Reddy et al.
[23] reported that, microcrystalline cellulose supported Cu-
nanoparticles catalyzed Aza-Michael reaction of primary and
secondary amines. In their report, they used 3.6 mol% of the copper
nanoparticles and obtained similar results. Whereas, we used only
0.016 mol% of the CuN@PHA which is 225 times lower catalytic
loading compare to their report.
Scheme 2. Chemo selectivity of Michael addition reaction
Hot filtration test of the Click reaction
Recycling of copper complex 3 and CuN@PHA
The heterogeneity of the supported catalyst in the reaction medium
is another vital issue. We performed hot filtration experiment to
check whether the catalytic reaction proceeded through
heterogeneous condition or not (Fig. 7). Thus, we carried out Click
reaction of benzyl azide and phenylacetylene according to Table 2.
The reaction was performed for one hour under the identical
condition and then the reaction mixture was filtrated at hot
condition and the filtrate was further heated under the identical
reaction conditions and observed no reaction was further preceded
at all. The ICP-AES analysis of filtrate revealed that no copper
species was latched out into the aqueous solution. Thus, it is
Considering the importance of reusability of the catalyst in
heterogeneous catalysis system, we concentrated recycling our
copper complex 3 and CuN@PHA and the results are shown in Fig.
6. After completion of the first run, the reaction mixture was
filtrated and the catalyst was washed with ethyl acetate/methanol.
The solid catalysts were dried at 80 °C under vacuum and then used
it in the next run without changing the reaction conditions. The
copper complex 3 and CuN@PHA were observed to work upto six
times without significant loss of its catalytic activity. The only
negligible loss of catalytic activity was found under the same
reaction conditions as for initial run. The small reduction of catalytic
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Conclusions
7
8
9
In summary, we have synthesized khaya cellulose supported
poly(hydroxamic acid) copper complex and copper nanoparticles
and successfully
Click and Michael addition reactions
applied in the
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The catalysts
(0.05 to 0.008 mol%) promoted C-N bond formation
efficiently
reaction to produce their corresponding products with excellent
yields as well as exhibited magnificent reusability without any
significant degradation of its reactivity for several cycles, promising
a reusable environment-friendly catalyst for practical applications.
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Acknowledgements
This work is supported by Ministry of Education Malaysia, fund no.
RDU 140124 and RDU 140343. Authors are grateful to Nor Hafizah
Bt Zainal Abidin, scientific officer, and central lab, University
Malaysia Pahang.
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Graphical Abstract:
sodium
ascorbate
hydrazine
hydrate
1st run: 96%, 6th run: 83%
1st run: 95%, 6th run: 88%