Copper immobilized on biomimetic assembled calcium carbonate/carboxymethylcellulose hybrid: a highly active recoverable catalyst for CuAAC reactions

Article abstract of DOI:10.1007/s11164-021-04474-y

A novel copper immobilized on biomimetic assembled carboxymethylcellulose/calcium carbonate hybrid (Cu^II@CMC/CaCO₃) as an efficient heterogeneous catalyst for the synthesis of 1,2,3-triazoles has been described herein. The fabrication of Cu^II@CMC/CaCO₃ is accomplished through a bioinspired mineralization process using sodium carboxymethylcellulose (CMC-Na) as the template and ion exchange agent, while the metathesis, nucleation, assemble, hybridization, and immobilization of Cu(II) occurred by successful treatment with CaCl₂, Na₂CO₃, and CuSO₄ in water at room temperature. The resultant Cu^II@CMC/CaCO₃ hybrid was well characterized by various analyses such as FT-IR, XRD, SEM, EDX, EDX-mapping, TEM, and TGA techniques. In the presence of low copper loading of Cu^II@CMC/CaCO₃ hybrid, benzylic halides, azide, and alkynes proceeded smoothly to afford 1,4-disubstituted 1,2,3-triazoles in high yields. The catalyst can be conveniently recovered from the reaction mixture by filter and reused for at least 5 consecutive runs with a slight drop in its catalytic activity. The remarkable activity and stability of the catalyst may be attributed to the coordination of both carboxyl and hydroxyl groups of the hybrid of CMC/CaCO₃.

Full text of DOI:10.1007/s11164-021-04474-y

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-021-04474-y
Copper immobilized on biomimetic assembled calcium
carbonate/carboxymethylcellulose hybrid: a highly active
recoverable catalyst for CuAAC reactions
1
1
1
1,2
Mingjuan Zhang · Jinxi Xu · Tianzhu Zhang · Yiqun Li
Received: 28 July 2020 / Accepted: 19 April 2021
©
The Author(s), under exclusive licence to Springer Nature B.V. 2021
Abstract
A novel copper immobilized on biomimetic assembled carboxymethylcellulose/
II
calcium carbonate hybrid (Cu @CMC/CaCO ) as an efcient heterogeneous cata-
3
lyst ꢀor the synthesis oꢀ 1,2,3-triazoles has been described herein. The ꢀabrication
II
oꢀ Cu @CMC/CaCO is accomplished through a bioinspired mineralization process
3
using sodium carboxymethylcellulose (CMC-Na) as the template and ion exchange
agent, while the metathesis, nucleation, assemble, hybridization, and immobilization
oꢀ Cu(II) occurred by successꢀul treatment with CaCl , Na CO , and CuSO in water
2
2
3
4
II
at room temperature. The resultant Cu @CMC/CaCO hybrid was well character-
3
ized by various analyses such as FT-IR, XRD, SEM, EDX, EDX-mapping, TEM,
II
and TGA techniques. In the presence oꢀ low copper loading oꢀ Cu @CMC/CaCO
3
hybrid, benzylic halides, azide, and alkynes proceeded smoothly to aꢁord 1,4-dis-
ubstituted 1,2,3-triazoles in high yields. The catalyst can be conveniently recovered
ꢀ
rom the reaction mixture by ꢂlter and reused ꢀor at least 5 consecutive runs with a
slight drop in its catalytic activity. The remarkable activity and stability oꢀ the cata-
lyst may be attributed to the coordination oꢀ both carboxyl and hydroxyl groups oꢀ
the hybrid oꢀ CMC/CaCO .
3
Keywords Biomimetic synthesis · Carboxymethylcellulose/calcium carbonate
hybrid · Copper · CuAAC reaction
*
Yiqun Li
tlyq@jnu.edu.cn
1
2
Department oꢀ Chemistry, Jinan University, Guangzhou 510632, People’s Republic oꢀ China
CAS Key Laboratory oꢀ Synthetic Chemistry oꢀ Natural Substances, Shanghai
Institute oꢀ Organic Chemistry, Chinese Academy oꢀ Sciences, Shanghai 200032,
People’s Republic oꢀ China
Vol.:(012
1
3456789)
3

M. Zhang et al.
Introduction
1
,2,3-Triazoles are stable N-rich ꢂve-membered heterocyclic architectures ꢀor tolerating
moisture, air, light, harsh conditions, and metabolism in living organisms and proved
to be versatile synthetic intermediates ꢀor agricultural chemicals, pharmaceuticals, and
ꢀ
unctional materials [1–3]. The most powerꢀul tool ꢀor the synthesis oꢀ 1,2,3-triazoles
is based on the 1,3-dipolar cycloaddition oꢀ alkyne and azide. The ꢂrst uncatalyzed
,3-dipolar cycloaddition oꢀ alkyne and azide aꢁorded a mixture oꢀ 1,4- and 1,5-sub-
1
stituted 1,2,3-triazoles, respectively, under harsh condition ꢂrst reported in 1893 by
Michael and later modiꢂed by Huisgen (Scheme 1) [4]. In 2002, Sharpless and Meldal
independently discovered the Cu-catalyzed 1,3-Huisgen reaction with high regioselec-
tivity to produce the exclusively the 1,4-disubstituted isomer under mild reaction con-
ditions [5, 6]. These Cu-catalyzed azide–alkyne cycloadditions were later deꢂned as
CuAAC reactions, or more commonly reꢀerred to as click reactions (Scheme 1). Since
then, the CuAAC reaction has been established to be a powerꢀul tool in organic syn-
thesis, medicinal chemistry, polymer chemistry, and surꢀace modiꢂcations owing to
its unique ꢀeatures such as high efciency, mild conditions, excellent yields, and high
regioselectivity [7–10]. In recent years, several reviews have thoroughly highlighted the
progress oꢀ CuAAC reactions and a plethora oꢀ homogeneous and heterogeneous catal-
ysis have been documented in the literature [10–13]. This CuAAC reaction is typically
accomplished using homogeneous copper(I) sources such as CuI, CuBr, and CuCl [14].
However, Cu(I) species are easily oxidized to Cu(II), and/or disproportionate to Cu(0)
and Cu(II) owing to its thermodynamic instability [15]. To overcome this problem,
ligand stabilized Cu(I) catalytic system has been developed. In particularly, a series
oꢀ ligands such as PPh , iminopyridine, nitrogen ligands, N-heterocyclic carbene have
3
been successꢀully employed to protect Cu(I) intermediates ꢀrom oxidation and dispro-
portionation, and hamper undesired side-product ꢀormation [15, 16]. Recent research
results indicated that homogeneous Cu(II) salts like CuSO , CuCl , and Cu(OAc) , etc.,
4
2
2
together with a reductant (usually sodium ascorbate) could be adopted as catalysts ꢀor
CuAAC reactions. Despite their excellent catalytic perꢀormance, there are one or more
disadvantages such as the use oꢀ excess organic solvent, low yields, long reaction times,
high temperature, tedious isolation, introduction oꢀ stabilizing ligands, requirement oꢀ
excessive reducing agent, and severely contamination oꢀ the product with transition
metal catalyst and possible ligand residues.
Heterogeneous catalysis has salient ꢀeatures such as easy recovery and good recy-
clability. Thereꢀore, it is not surprising that many attempts have been made on hetero-
genization oꢀ homogeneous catalyst on an insoluble support material in recent years to
aim to separation and reuse oꢀ the CuAAC catalysts ꢀrom the reaction mixture in more
eꢁective ways to tackle the obstacles oꢀ homogeneous catalysis. Recently, the pace
Scheme 1 Thermal Huisgen’s reaction and Cu-catalyzed azide–alkyne cycloaddition
1
3

Copper immobilized on biomimetic assembled calcium…
oꢀ researches in the scope oꢀ heterogeneous catalysis ꢀor CuAAC is so ꢀast that many
reported heterogeneous copper catalysts have documented in the literature [13, 15,
II
1
7, 18]. For instance, magnetic Cu -CMC-Fe O hybrid materials [19], cuttlebone@
3
4
CuCl [20], Cu(I)/microporous Schiꢁ base network [21], NovaPEGBimPy /CuSO
2
2
4
[
22], the copper(I) complex oꢀ polymer-supported tris(triazolyl)methanol [23], thermo-
responsive P(TBTACu-co-NIPAM) catalyst [24], nano-ꢀerrite-glutathione-copper [25],
II
Cu –hydrotalcite [26], Cu(OH) /TiO [27], ionic polymer supported copper(I) [28],
x
2
copper-alginates [29], TG-TBTA-CuPF [30], CuI/Amberlyst A-21 catalyst [31], Cu/C
6
[32], etc., have been documented.
Noticeably, among the homogeneous Cu(II) catalytic system, the eꢁect oꢀ coun-
terion oꢀ Cu(II) salts was independently studied using CuCl , CuSO , and Cu(OAc)
2
2
4
by L. Zhu et al.[33] and M. L. Kantam et al. [34]. Although three counterions gave
satisꢀactory yields, the activity oꢀ these systems was ꢀound to depend on the nature
−
−
2−
oꢀ the counter-ion in the order: AcO >Cl >SO . Unlike CuSO and CuCl ,
4
4
2
Cu(OAc) is the best catalyst in t-BuOH to aꢁord highest yields in shortest time.
2
Even so, there is no report oꢀ using supported Cu(OAc) as a catalyst ꢀor CuAAC
2
reactions.
Recently, natural biominerals have emerged as viable alternatives to conventional
support materials, as robust, readily available, high-surꢀace-area heterogeneous cata-
lyst supports. Some literature studies reported the use oꢀ naturally biominerals as
supports ꢀor immobilization oꢀ metal catalysts, like oyster shell powder-supported
CuBr (OSPs-CuBr) [35], oyster shell powder (OSP)-supported CuCl (OSP‐CuCl )
2
2
[
36], pearl shell powder-supported palladium (Pd/shell powders, Pd/SP) [37], and
Ag nanoparticle-loaded eggshell (Ag NPs/eggshell) [38], which demonstrate that
these catalysts are promising ꢀor various organic reactions such as CuAAC reactions,
A couplings, reductive homocoupling oꢀ aromatic halides, benzene oxidation, and
3
so on. The research results clearly showed that these naturally biomineral-supported
metal catalysts exhibit superior catalytic activity compared with the unsupported
counterparts. The remarkable catalytic activity has been attributed to the chelation
oꢀ metal species with the surꢀace chitin, protein molecules oꢀ the supported naturally
biomimetic powders. Thereꢀore, the excellent catalytic perꢀormance oꢀ Cu(OAc)
2
ꢀ
or CuAAC reactions and metal catalysts immobilized on natural biominerals has
deeply impressed and aꢁorded us important inspiration ꢀor catalysts design and
synthesis.
Sodium carboxymethylcellulose (CMC-Na), one water-soluble cellulose deriva-
−
+
tives bearing a plenty oꢀ –COO Na groups and –OH groups on its molecular chain,
is capable oꢀ exchanging and thus chelating with metal cations [39, 40]. Thus, neg-
atively charged carboxylate groups are suggested to have the ability to serve as a
template to chelate calcium ions and induce the nucleation oꢀ the related CaCO
3
biominerals in nature. Based on combination oꢀ these properties, we here wish to
II
report a novel biomimetic approach ꢀor preparation oꢀ Cu @CMC/CaCO cata-
3
lyst in which CMC-Na backbone/side carboxylic and hydroxyl groups have a large
impact not only on the mineralization oꢀ CaCO but also on the immobilization oꢀ
3
metal catalyst and ꢀurther modulate their catalytic activity. The catalytic activity
II
and recyclability oꢀ the Cu @CMC/CaCO catalyst have been examined using the
3
CuAAC reactions (Scheme 1).
1
3

M. Zhang et al.
Results and discussions
II
Preparation and characterization of Cu @CMC/CaCO catalysts
3
II
Initially, in the achievement oꢀ this purpose was the ꢀabrication oꢀ Cu @CMC/
CaCO hybrid catalyst. The catalyst was prepared by a ꢀacile biomimetic selꢀ-assem-
3
ble method using CMC-Na as template and exchange reagent successively treated
with CaCl and Na CO in water to control—nucleate and induce the growth oꢀ
2
2
3
CMC-Na/CaCO hybrid, ꢀollowed by the Cu(II) immobilization on CMC-Na/CaCO
3
3
4
hybrid by the ion exchange reaction oꢀ CMC-Na trapped in CaCO with CuSO
3
solution being achieved. The preparation approach is depicted in Scheme 2.
II
Next, the biomimetic selꢀ-assembled Cu @CMC/CaCO catalysts were well
3
characterized by ICP-AES, FT-IR, XRD, SEM, EDX, TEM and TGA techniques.
II
The FT-IR oꢀ CMC-Na, Na-CMC/CaCO , and Cu @CMC/CaCO are shown in
3
3
−1
Fig. 1. In curve a, the broad band around 3492 cm conꢂrms the O–H bond vibra-
tion, and peak located around 2915 cm− can be assigned to the asymmetric and
1
II
Scheme 2 Schematic preparation oꢀ Cu @CMC/CaCO via selꢀ-assemble process between carboxylate
3
groups oꢀ CMC-Na with calcium and copper ions
1
3

Copper immobilized on biomimetic assembled calcium…
symmetric C–H stretching modes [41]. The characteristic absorption peaks at 1459
−
1
−
+
and 1421 cm oꢀ CMC-Na are assigned to the carboxylate (–COO Na ) asym-
−
1
metric and symmetric stretching vibration [41]. The peak at 1053 cm is attrib-
uted to C–O–C bond vibration [41]. In curve b, and c, the sharp peaks appeared at
−1
−1
8
75 cm , and 707 cm are related to characteristic Ca–O bond oꢀ calcite CaCO ,
3
which is basically consistent with the vibration absorption peaks oꢀ Ca–O in the
−
literature [41]. Compared to curve a, the characteristic –COO peaks oꢀ Na-CMC/
II
−1
CaCO and Cu @CMC/CaCO are turned broad and red shiꢀted to1498 cm and
3
3
−1
1
438 cm , respectively, illustrating the interactions oꢀ CMC with CaCO and coor-
3
dination oꢀ CMC with Cu(II) ions.
Figure 2 shows XRD patterns oꢀ CMC-Na, surꢀace-modiꢂed Na-CMC/CaCO
3
II
and Cu @CMC/CaCO . In curve b and c, diꢁraction peaks oꢀ (012), (104), (110),
3
(
113), (202), (018), (116), and (122) came ꢀrom a typical calcite oꢀ CaCO crystal
3
II
[
41]. These peaks do not change in Cu @CMC/CaCO , indicating that the immo-
3
bilization oꢀ Cu(II) does not damage the crystal structure oꢀ CaCO . Although all
3
peaks are very well matched with the calcite structure, the broaden peaks in curve
c may be caused by vigorous hybridization oꢀ CMC with CaCO and interaction oꢀ
3
Cu(II) with CMC/CaCO hybrids in molecular level. Moreover, Cu(II)-related peaks
3
were not detected in the XRD pattern oꢀ the catalyst which implies that Cu(II) was
dispersed in the CMC matrix as an amorphous ꢀorm.
II
The SEM images oꢀ the surꢀace morphology oꢀ ꢀresh and the Cu @CMC/CaCO
3
aꢀter third use are shown in Fig. 3. The SEM images clearly show that all these
II
Cu @CMC/CaCO catalysts have similar microparticles microstructures in varying
3
sizes and shapes with rough surꢀace. This rough texture aꢁords crucial ꢀunctions
to enlarge its contact area and thus increases the loading amount oꢀ Cu(II) cations
as well as ꢀacilitate the better mass transꢀer. However, microparticles with slight
changes are visible aꢀter three times reuse (image b) in CuAAC reaction.
Energy-dispersive X-ray spectroscopy (EDX) analysis provides the local inꢀorma-
tion oꢀ various elements. The existence oꢀ metallic elements Ca, Cu and non-metallic
Fig. 1 The FT-IR oꢀ CMC-Na
(
a), Na-CMC/CaCO (b) and
3
(a)
II
Cu @CMC/CaCO (c)
3
_
C-H
C-H
-_COO C-O-C
-COO
O-H
O-H
(
b)
C-O-C
Ca-O
_
Ca-O
-COO
(
c)
C-H
Ca-O
C-O-C
Ca-O
COO -COO
O-H
_
_
-
4000 3500 3000 2500 2000 1500 1000
500
-
1
Wave number(cm )
1
3

M. Zhang et al.
Fig. 2 XRD oꢀ CMC-Na (a),
II
Na-CMC/CaCO (b) and Cu @
3
CMC/CaCO (c)
3
(a)
（
104
（
）
（
113
）
）
（
116
）
（
（
202
）
110
（
018）
(
b)
（
012
）
122
）
(
c)
2
0
40
60
80
2
-Theta (degree)
Fig. 3 The SEM oꢀ ꢀresh catalyst (a) and the catalyst aꢀter the third use (b)
elements C, O is clearly shown in Fig. 4. Obviously, the presence oꢀ these elements
has been successꢀully anchored on the CMC/CaCO .
3
II
The element mapping ꢀor the selected area oꢀ Cu @CMC /CaCO hybrid is
3
shown in Fig. 5 which shows that C, O, Ca and Cu are dispersed in a relatively
II
uniꢀorm ꢀorm in Cu @CMC/CaCO catalyst. These maps distinctly conꢂrmed the
3
existence oꢀ C, O, Ca, and Cu throughout the hybrid material in a homogeneous
dispersion.
II
II
The TEM images oꢀ the ꢀresh catalyst Cu @CMC/CaCO and the Cu @CMC/
3
II
CaCO catalyst aꢀter third use are presented in Fig. 6. As can be seen, the Cu @
3
CMC/CaCO is amorphous with black color showing CaCO core surrounded by
3
3
gray and ꢃuꢁy CMC shell. The particle size is measured by ImageJ soꢀtware. The
II
average size oꢀ the ꢀresh and the used Cu @CMC/CaCO catalyst is in the scope oꢀ
3
1
00–105 nm and 105–120 nm, respectively, showing a slight aggregation oꢀ used
catalyst.
In most cases, the CuAAC reaction is perꢀormed on thermal conditions. The sta-
II
bility oꢀ the Cu @CMC/CaCO was assessed by the thermogravimetric analysis
3
1
3

Copper immobilized on biomimetic assembled calcium…
II
Fig. 4 The EDX oꢀ Cu @CMC/CaCO3
II
(
TGA). The TGA curves oꢀ the CMC-Na, and Cu @CMC/CaCO are depicted in
3
Fig. 7. As can be seen ꢀrom curve a, the incipient weight loss oꢀ CMC-Na occurred at
the range oꢀ 50–100 °C ascribed to the release oꢀ physically adsorbed moisture; the
sharply weight loss in the region between 300 and 325 °C is attributed to the decom-
II
position oꢀ CMC. By comparison with CMC-Na, the main weight loss oꢀ Cu @
CMC/CaCO observed in the scope oꢀ 250–300 °C is ascribed to the decomposition
3
II
2+
oꢀ CMC, implying that Cu @CMC/CaCO is not a physical mixture oꢀ Cu with
3
II
CMC/CaCO , but a metal complex. Moreover, the Cu @CMC/CaCO presented
3
3
higher ash content, which is the desired copper residue. The TGA results indicate
II
that Cu @CMC/CaCO hybrid has good thermal stability ꢀrom room temperature to
3
2
50 °C and thus can be perꢀormed in the described experimental conditions.
II
Application of Cu @CMC/CaCO hybrids in CuAAC reaction for the synthesis
3
of 1,2,3‑triazoles
The CuAAC reaction is generally perꢀormed using a catalytic amount oꢀ Cu
(
II) with a reducing agent such as sodium ascorbate. The direct use oꢀ Cu(I) or
its clusters is also possible; however, there is ꢀormation oꢀ undesirable alkyne-
alkyne homocoupling product. To obtain the optimal reaction conditions ꢀor
CuAAC reactions, the reaction oꢀ benzyl bromide (1.0 mmol), phenyl acetylene
(
1.0 mmol), sodium azide (1.2 mmol), sodium ascorbate (10 mol%) was chosen
as a model to systematically evaluate under various conditions including solvent,
the loading amount oꢀ catalyst, and reaction temperature. The results are sum-
marized in Table 1. At the beginning, diꢁerent solvents were screened to select
the suitable solvent. Protic polar solvents including EtOH, 75% EtOH, t-BuOH,
aqueous t-BuOH, MeOH, and H O as well as aprotic polar solvents including
2
1
3

M. Zhang et al.
II
Fig. 5 The element mapping oꢀ catalyst Cu @CMC/CaCO3
CH CN, DMF, and DMSO aꢁorded moderate to high product yields (Table 1,
3
entries 2–16), while poor yield was observed in toluene (Table 1, entry 1). Based
on the screening ꢂndings, H O was chosen as the most suitable solvent ꢀor ꢀurther
2
II
applications. Subsequently, the catalytic amount oꢀ the Cu @CMC/CaCO was
3
explored. It was ꢀound that 2 mol% oꢀ Cu is the optimal amount oꢀ the catalyst
1
3

Copper immobilized on biomimetic assembled calcium…
Fig. 6 The TEM images oꢀ ꢀresh catalyst (a) and catalyst aꢀter third use (b)
Fig. 7 The TGA analysis oꢀ
II
CMC-Na (a) and Cu @CMC/
CaCO (b)
3
(
(
b)
a)
because it gave the best yield (Table 1, entry 12). Moreover, no signiꢂcant pro-
motion in the yield was observed increasing the amount oꢀ catalyst to 3 mol%
and even to 4 mol% (Table 1, entries 13 and 14). On the contrary, decreasing
the amount oꢀ catalyst reduced the yield oꢀ the product (Table 1, entry 11). As
expected, in the absence oꢀ the catalyst, no desired product was ꢀound (Table 1,
entry 10). These results indicated that the catalyst played a crucial role in the
reaction. Finally, having optimized the solvent and dose oꢀ catalyst ꢀor the model
reaction, we proceeded to investigate the adoption oꢀ diꢁerent temperatures
including 70, 50, and 25 °C. Decreasing the reaction temperature ꢀrom 70 to 50
and 25 °C, the yields decreased ꢀrom 93 to 80 and 63%, respectively (Table 1,
entries 12–16). These ꢂndings had considerable negative impact on the product
yields. Thereꢀore, the optimal condition was that oꢀ benzyl bromide (1.0 mmol),
phenyl acetylene (1.0 mmol), sodium azide (1.2 mmol), sodium ascorbate
1
3

M. Zhang et al.
Table 1 Optimization oꢀ the reaction conditionsa
b
Entry
Solvent
Amount oꢀ catalyst
mmol% oꢀ Cu)
Temp. (°C)
Time (h)
Yield (%)
(
1
2
3
4
5
6
7
8
9
Toluene
MeCN
DMF
DMSO
EtOH
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
0
1.0
2.0
3.0
4.0
2.0
2.0
70
70
70
70
70
70
70
70
70
70
70
70
70
70
50
25
9
4
3
3
3
2
3
2
2
2
2
1
1
1
2
6
Trace
62
75
78
76
82
80
90
75% EtOH
t-BuOH
H O/t-BuOH (4/1, v/v)
2
MeOH
65
NP
c
10
11
12
13
14
15
16
H O
2
H O
80
93
93
93
80
63
2
H O
2
H O
2
H O
2
H O
2
H O
2
a
Reaction conditions: benzyl bromide (1.0 mmol), phenyl acetylene (1.0 mmol), sodium azide
II
(
1.2 mmol), sodium ascorbate (10 mol%), Cu @CMC/CaCO (catalytic amount oꢀ Cu), solvent (3 mL)
3
at 70 °C
b
Isolated yields
NP reꢀers to no production
c
II
(
10 mol%), and Cu @CMC/CaCO (2 mol% oꢀ Cu) in H O (3 mL) at 70 °C ꢀor
3
2
speciꢂc time indicated by TLC.
With the optimal condition established, the domain oꢀ the reactions using a wide
range oꢀ benzyl halides, various alkynes, and sodium azide were explored, and the
obtained results are summarized in Table 2. In this catalytic system, diꢁerent ben-
zyl halides bearing either electron-donating or electron-withdrawing substituents
proceed well to aꢁord the desired products in good-to-excellent yields. The results
illustrate that the electronic ꢀactors oꢀ the substrates do not have signiꢂcant eꢁect
II
on the product yields attributing to the high catalytic activity oꢀ Cu @CMC/CaCO
3
hybrid catalyst. Notably, benzyl chloride took a slightly prolonged time as compared
with that ꢀor aryl bromide counterparts due to its lower reactivity (Table 2, entries 1
and 2, 7 and 8, 13 and 14). Furthermore, aliphatic halides (Table 2, entries 22–23)
and aliphatic alkyne (Table 2, entry 24) could work and produced the corresponding
products in moderate to good yields.
1
3

Copper immobilized on biomimetic assembled calcium…
II
Table 2 Cu @CMC/CaCO ‐catalyzed synthesis oꢀ 1,4-disubstituted 1,2,3-triazoles through one‐pot
3
CuAAC reactionsa
b
Entry
R1
R2
X
Time (h)
Yield (%)
Product
1
2
3
4
5
6
7
8
9
Ph
Ph
4-F-C H -
3-F-C H -
4-Cl-C H -
3-Cl-C H -
3-CH -C H -
4-CH -C H -
4-NO -C H -
4-OCF -C H -
4-Br-C H -
4-Br-C H -
Ph
Ph
4-NO -C H -
4-OCF -C H -
4-Br-C H -
3-Cl-C H -
Ph
4-Br-C H -
4-CN-C H -
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Br
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Cl
Br
Cl
Br
Br
Br
Br
Br
Br
Br
I
1
93
89
85
82
87
88
90
88
83
88
91
84
88
86
80
82
87
84
88
90
82
43
52
83
4a
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4j
4k
4k
4l
1.5
2.5
3
3
3
3
2.5
4
2.5
1.5
2.5
2.5
4
6
4
2.5
3
2
2.5
3
5
5
5
6
4
6
4
6
4
6
4
3
6
4
3
6
4
2
6
4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
3
6
4
6
4
6
4
4-Me-C H -
4-Me-C H -
4-Me-C H -
4-Me-C H -
4-Me-C H -
4-Me-C H -
2-Py
2-Py
2-Py
Ph
6
4
6
4
2
6
4
6
4
4m
4n
4o
4p
4q
4r
4s
4t
3
6
4
6
4
6
4
6
4
6
4
6 4
6
4
6
4
C H -
2
5
CNCH2-
Ph
Ph
Oct
Br
Br
4u
a
Reaction conditions: benzyl halide (1.0 mmol), alkyne (1.0 mmol), sodium azide (1.2 mmol), sodium
II
ascorbate (10 mol%), Cu @CMC/CaCO (2.0 mol% oꢀ Cu), solvent (H O, 3 mL) at 70 °C
3
2
b
Isolated yields
II
The recyclability oꢀ Cu @CMC/CaCO catalyst was examined using the model
3
II
reaction under the optimal condition. At the end oꢀ the reaction, Cu @CMC/CaCO
3
catalyst was separated and reused directly in the subsequent run without any ꢀur-
ther treatment. As seen ꢀrom Fig. 8, slight dropping oꢀ the catalytic perꢀormance
was observed aꢀter each run. Notably, the copper content oꢀ the used catalyst aꢀter
three cycles was measured to be 3.508 mmol/g by ICP analysis, by comparison with
the data oꢀ ꢀresh catalyst (4.040 mmol/g); a slight Cu leaching ꢀrom catalyst was
1
3

M. Zhang et al.
observed. Thus, the product yields decrease seemed to be the tiny amounts oꢀ Cu
leaching and slight aggregation oꢀ catalyst (Figs. 3b, 6b, 8).
Proposed mechanism for the carboxyl‑chelation assisted CuAAC reaction
Based on the dinuclear copper mechanism proposed by Fokin et al. [42], we pos-
tulate the plausible carboxylic-modulated mechanism ꢀor the CuAAC (Scheme 3).
Initially, the Cu(I) species is ꢀormed in situ ꢀrom Glaser coupling [43] initiated by
II
Cu(II) species in Cu @CMC/CaCO precatalyst. The Cu(I) species interact with
3
terminal alkyne to generate copper–acetylide intermediate (A) and release a proton.
Secondly, the complex (A) reacts with azide which is activated by another Cu(I)
species to ꢀorm the dinuclear copper intermediate (B). Thirdly, rearrangement oꢀ
intermediate (B) leads to the ꢀormation oꢀ the copper metalated triazolide (C) and
release oꢀ the catalytic Cu(I) species. Finally, the intermediate (C) captures a proton
to produce the corresponding triazole and regenerate the Cu(I) species. Noticeably,
CMC in this catalytic cycle provide the carboxylic groups to tune the activity oꢀ
Cu(I) species on the catalyst.
Conclusion
In this work, we have successꢀully developed an efcient biomimetic approach ꢀor
the preparation oꢀ Na-CMC/CaCO biomimetic minerals and ꢀurther employed it
3
II
as a support to anchor Cu(II) to assemble Cu @CMC/CaCO nanohybrid catalyst
3
using carboxymethylcellulose as a template and ion exchanger as well as modula-
tor oꢀ catalytic perꢀormance. The as-prepared biomimetic nanocatalyst is well char-
acterized by ICP, FT-IR, SEM, EDX, TEM, XPS, and TGA analyses. It has been
II
certiꢂed that Cu @CMC/CaCO clearly exerts versatile catalytic activity toward the
3
CuAAC reactions. The remarkable activity and stability oꢀ the catalyst have been
ascribed to the coordination oꢀ both carboxyl and hydroxyl groups oꢀ the hybrid oꢀ
CMC/CaCO . Moreover, there is no obvious loss oꢀ the catalytic activity when the
3
140
120
100
8
6
4
2
0
0
0
0
0
1
2
3
4
5
Yields(%)
Time(min)
II
Fig. 8 Recyclability oꢀ Cu @CMC/CaCO catalyst in the model reaction
3
1
3

Copper immobilized on biomimetic assembled calcium…
Scheme 3 Conceivable catalytic pathway oꢀ the carboxyl-chelated-copper-catalyzed CuAAC reaction
based on Fokin’s proposal
catalyst is reused up to 5 runs. Thereꢀore, high catalytic perꢀormance, reusability oꢀ
catalyst, wide substrate scope, short reaction time, and mild condition are the salient
ꢀ
eatures oꢀ this green catalytic process, which makes it more competitive ꢀor practi-
cal applications.
Experimental
Materials and methods
Sodium carboxymethylcellulose (CMC-Na, Mw 250,000) was purchased ꢀrom com-
mercial sources and used without ꢀurther treatment; all other chemicals were AR or
CP grade and used as received.
Melting points were measured by Electrothermal X microscopic digital melt-
6
ing point apparatus. All reactions were perꢀormed on magnetic agitator type WH
2
20. The copper content oꢀ catalyst was measured by PerkinElmer Optima 20,000 V
Inductively coupled plasma spectrometer. The copper content oꢀ catalyst was
1
3

M. Zhang et al.
measured by PerkinElmer Optima 20,000 V Inductively coupled plasma spectrom-
eter. Flourier transꢀorm inꢀrared spectra (FT-IR) were recorded on a Nicolet 6700
spectrophotometer in KBr pellet. Scanning electron microscopy (SEM) were tested
with Philips XL 30E scanner, and energy-dispersive spectroscopy (EDX) was con-
ducted with a Hitachi SU8010 instrument. X-ray powder diꢁraction (XRD) data
were collected on an MSALXRD2 diꢁractometer under ambient conditions using
Cu Ka radiation in a range oꢀ Bragg’s angles (20–80 °C). Transmission electron
microscopy (TEM) was validated by TEM-100CX instrument. Thermogravimetric
analysis (TGA) was gained on a SDTQ 600 equipment. X-ray photoelectron spec-
troscopy (XPS) was acquired on a Thermo ESCALAB 250XI spectrometer with
1
monochromatic Al Kα radiation. H NMR (300 MHz) spectra were recorded by
a Bruker-300 Avance Spectrometer with CDCl as solvent with TMS as internal
3
standard.
II
Biomimetic preparation of Cu @CMC/CaCO hybrid catalyst
3
Firstly, CaCl (2.2 g, 20 mmol) was slowly mixed with CMC-Na solution (0.4 wt%,
2
5
00 mL) under vigorously agitation at room temperature ꢀor 1 h to obtain a clear
solution. Secondly, the Na CO solution (20 mmol, 500 mL) was quickly poured
2
3
into the as-prepared CMC/CaCl mixture with constant stirring at room tempera-
2
ture ꢀor 30 min. Then, the white CMC-Na/CaCO microspheres were separated
3
by centriꢀugation at 3000 r/min ꢀor 5 min and then washed with a large amount oꢀ
deionized water till the ꢂltrate turned to neutral. The collected white powders were
then dried in the vacuum to constant weight. Finally, the resultant CMC-Na/CaCO
3
.
hybrid (1.0 g) was immersed in 0.1 mol/L Cu(OAc) H O ꢀor 72 h under mild agi-
2
2
tation at room temperature to ensure the completion oꢀ metathesis oꢀ Cu(II) with
CMC-Na/CaCO . The blue solid was separated ꢀrom the solution by suction and
3
washed with deionized water and ethanol successively and thoroughly, then dried
II
in vacuum to constant weight to provide Cu @CMC/CaCO as blue powders. The
3
loading Cu content was determined by coupled plasma (ICP-AES) analysis to be
4
.040 mmol/g.
General procedure for the one‑pot CuAAC reaction
A mixture oꢀ benzyl halides (1.0 mmol), terminal alkynes (1.0 mmol), NaN
3
3
II
(
1.2 mmol), sodium ascorbate (10 mol%), a catalytic amount oꢀ Cu @CMC/CaCO
catalyst (2.0 mol% oꢀ Cu), and 3.0 mL H O were charged into a ꢃask. The reaction
2
mixture was heated at 70 °C ꢀor a speciꢂc time with constant stirring. The progress
was tracked by TLC. Aꢀter completion oꢀ the reaction, ethyl acetate was added to
the ꢃask and the catalyst was ꢂltered by suction, washed with enough ethyl acetate,
and dried in vacuum ꢀor the next run. The resulting mixture was washed with brine
and dried over anhydrous Na SO and evaporated in vacuum using a rotary evapora-
2
4
tor to obtain the crude product. The desired pure products were ꢀurther puriꢂed by
recrystallization with ethanol/H O mixed solvent. All the products are known, and
2
1
3

Copper immobilized on biomimetic assembled calcium…
1
their melt point and H NMR data were ꢀound to be consistent with those reported in
the literature.
Supplementary Information The online version contains supplementary material available at https://doi.
org/10.1007/s11164-021-04474-y.
Acknowledgements We are grateꢀul to the Natural Science Foundation oꢀ Guangdong Province (No.
2
020A1515010399) ꢀor ꢂnancial support.
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