Solvent-free synthesis of propargylamines via A3 coupling reaction and organic pollutant degradation in aqueous condition using Cu/C catalyst

Article abstract of DOI:10.1002/aoc.5986

The present report focuses on the efficient and operationally simple synthesis of biomass-derived carbon as support to immobilize copper particles as a catalyst for the one-pot synthesis of propargylamines from furfural via the A³ coupling reaction. This new catalyst showed remarkable catalytic performance leading to a 97% yield within 5 h at 80 °C using 5 mg (0.0022 mmol Cu) of Cu/C catalyst under solvent-free condition. Moreover, nitro-substituted compounds such as 4-nitrophenol (4-NP) are highly toxic and not easily degradable. Hence, a quick and effective method is required to neutralize these toxic compounds. The synthesized active support Cu/C catalyst having various electron-donating groups containing small amounts of Cu plays an essential role in the catalytic reduction of 4-NP (0.1 g). Using only 3 mg (0.0013 mmol Cu) of Cu/C catalyst and NaBH₄ (10 mmol), a 99% yield (100% selectivity) in the aqueous condition at 25 °C was achieved. The catalytic reduction follows the pseudo-first-order kinetics with reaction rate constant of 0.028 s^?1. Moreover, results demonstrate that the Cu/C catalyst has superior catalytic activity due to the presence of electron-donating molecules such as O, S, and N atoms, which enable synergistic effect in enhancing the overall catalytic performance. Notably, the recoverability and recyclability of the synthesized catalyst were evaluated for up to four cycles, which confirmed its stability in these cycles.

Full text of DOI:10.1002/aoc.5986

Received: 31 May 2020
DOI: 10.1002/aoc.5986
Revised: 5 August 2020
Accepted: 8 August 2020
F U L L P A P E R
3
Solvent-free synthesis of propargylamines via A coupling
reaction and organic pollutant degradation in aqueous
condition using Cu/C catalyst
Pramod V. Rathod | John Marc C. Puguan | Hern Kim
Department of Energy Science and
The present report focuses on the efficient and operationally simple synthesis
of biomass-derived carbon as support to immobilize copper particles as a cata-
Technology, Myongji University,
Gyeonggi-do, Yongin, 17058, Republic of
Korea
3
lyst for the one-pot synthesis of propargylamines from furfural via the A cou-
Correspondence
pling reaction. This new catalyst showed remarkable catalytic performance
John Marc C. Puguan and Hern Kim, 2nd
Engineering Building, Rm 8845,
Department of Energy Science and
Technology, Myongji University,
ꢀ
leading to a 97% yield within 5 h at 80 C using 5 mg (0.0022 mmol Cu) of
Cu/C catalyst under solvent-free condition. Moreover, nitro-substituted com-
pounds such as 4-nitrophenol (4-NP) are highly toxic and not easily degrad-
able. Hence, a quick and effective method is required to neutralize these toxic
compounds. The synthesized active support Cu/C catalyst having various
electron-donating groups containing small amounts of Cu plays an essential
role in the catalytic reduction of 4-NP (0.1 g). Using only 3 mg (0.0013 mmol
116 Myongji-ro Cheoin-gu, Yongin,
Gyeonggi-do 17058, Republic of Korea.
Email: jmpuguan@mju.ac.kr;
hernkim@mju.ac.kr
Funding information
Cu) of Cu/C catalyst and NaBH (10 mmol), a 99% yield (100% selectivity) in
Korea Institute of Energy Technology
Evaluation and Planning; Ministry of
Trade, Industry & Energy, Grant/Award
Number: 20194010201750; the Korea
Institute of Energy Technology Evaluation
and Planning (KETEP) and the Ministry of
Trade, Industry & Energy (MOTIE) of the
Republic of Korea; Ministry of Education,
Grant/Award Number:
4
ꢀ
the aqueous condition at 25 C was achieved. The catalytic reduction follows
−
1
the pseudo-first-order kinetics with reaction rate constant of 0.028 s . More-
over, results demonstrate that the Cu/C catalyst has superior catalytic activity
due to the presence of electron-donating molecules such as O, S, and N atoms,
which enable synergistic effect in enhancing the overall catalytic performance.
Notably, the recoverability and recyclability of the synthesized catalyst were
evaluated for up to four cycles, which confirmed its stability in these cycles.
2020R1A6A1A03038817
K E Y W O R D S
4
-Nitrophenol, Cu/C catalyst, D-glucose, propargylamines, xylose
1
| INTRODUCTION
been utilized to deal with neuropsychiatric disorders such
as anxiety, Parkinson's disease, and depression. More-
over, they have been successfully applied in drugs such
The development of sustainable, green, biomass-derived
compounds into chemicals, biofuels, drugs, and various
materials is a significant research objective in modern
organic chemistry. For example, one-pot synthesis of
propargylamines derived from aldehyde derivatives
or xylose is an important study area because
propargylamines are used in the synthesis of chemicals
such as a peptides, isosteres, β-lactams, and natural
[
5]
as rasagiline, a potent cardiovascular drug. Because of
their vital role in many applications, numerous synthetic
methods for the preparation of propargylamines have
[1]
[
6–9]
been established.
However, improvements to these
synthetic methods continue to be explored. One approach
to the synthesis of propargylamines is the aldehyde–
3
alkyne–amine (A ) coupling reaction which utilizes vari-
[2–4]
products.
Moreover, numerous propargylamines have
ous kinds of metal-based catalysts such as Ag(I) salts,
Appl Organomet Chem. 2020;e5986.
wileyonlinelibrary.com/journal/aoc
© 2020 John Wiley & Sons, Ltd.
1 of 15
https://doi.org/10.1002/aoc.5986

2
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RATHOD ET AL.
[
10–12]
Cu(I) salts, and Fe(III) salts.
et al.
For example, Li
Therefore, robust and highly efficient heterogenous cata-
[13]
3
[20]
reported the A coupling reaction to produce
propargylamines catalyzed by AgI at 100 C in the pres-
ence of H O for 14 h. Furthermore, Wang et al.
established an InCl -catalyzed direct A coupling reaction
lysts are still being actively sought
(Scheme 1).
ꢀ
Meanwhile, rapid industrialization and innovative
advancements that have led to many improvements in
humanity's living conditions have also come at the cost
[
14]
2
3
3
ꢀ
in toluene at 120 C for 14 h. However, all these reported
of several environmental impacts such as H O scarcity,
2
catalysts were used in homogeneous form. For this rea-
son, the catalysts (i) were difficult to recover, regenerate
and reutilize; (ii) require large amounts of reagents;
water pollution, air pollution, and climate change. These
environmental impacts often stem from the release of
large amounts of industrial chemicals to the environment
that are difficult to degrade. Many of these industrial
chemicals are nitro-substituted compounds which are
among the most toxic and hazardous of chemicals. Nitro-
substituted compounds cause severe health hazards to
humans, animals, and aquatic life. For these reasons,
effective and efficient methods for the treatment of such
toxic compounds need to be developed. One treatment
strategy is via catalyzed reduction reactions.
(
(
iii) need highly moisture-sensitive reagents; and
iv) require exact reaction conditions that unfortunately
restrict their commercial application. To overcome these
issues, efforts have been devoted to construct various het-
3
erogeneous metal catalysts for the A coupling reaction
[15]
[16]
such as Cu–HAP,
immobilized NHC CuI complex,
zeolite, and supported Au/MIL-53.
nanocrystalline CuO,
silica-
AgY
[17]
[18]
Ni–Y zeolite,
[19]
However, these
heterogenous catalysts required toxic solvents, high metal
loading, various additives, and tedious catalyst separa-
tion, all of which limit their utilization and applicability.
The development of the catalytic reduction reactions for
converting nitro-substituted compounds to benign and
sometimes industrially important chemicals is usually
SCHEME 1 Previous protocols
compared with the present work.
ACN: Acetonitrile; AgNO3: Silver
nitrate; Ag-PAN-BIS-2: polymer
supported silver complex; Co3O4/NiO:
3D hierarchical Co3O4/NiO
microspheres; Cu/NH2/MCM-41:
Amine-Functionalized Mesoporous
Silica as a Support Copper(I);
Cu/WO272: bimetallic NP catalyst;
DMF: Dimethylformamide; EtOH:
Ethanol; NaBH4: Sodium borohydride;
Neat: Solvent-free; NI-Zn/AC-350:
Activated carbon supported bimetallic
catalysts; PANF TPA@NiCl2: fiber-
supported Ni(II) complex catalyst; PS-
PEG-BPY-CuBr2: copper(II)
−
bipyridine complex immobilized on
amphiphilic polystyrene
poly(ethylene glycol) (PS−PEG)
resin; RT: Room temperature; [TMG]
TFA]: Ionic Liquid (IL)
−
[

RATHOD ET AL.
3 of 15
performed using the test molecule 4-nitrophenol (4-NP). In
these catalyzed reduction reactions, 4-NP is converted to
sufficiently examined. The synthesis of an extremely effi-
cient Cu/C catalyst that promotes A coupling reactions with
3
4
-aminophenol (4-AP), which has a lower toxicity level and
low Cu loading in solvent-free catalytic transformations is
undoubtedly desired to achieve ideal and practical catalytic
[21]
may be utilized as a pharmaceutical intermediate. Cata-
lysts that have been used for these reactions include Au
nanoparticles,
Ag nanoparticles, and Ni nanoparticles.
reported systems require high-temperature and high-
pressure reactors, strong acid media, toxic solvents, and
[
28,29]
synthesis of propargylamines.
We believe that it would
[22]
[23]
SiO @CuxO@TiO2 heterostructures,
be very promising in terms of green technology, environ-
mental impact, process economics, and reaction efficiency to
examine a one-pot synthesis of important industrial
chemicals from biomass-derived intermediates such as furfu-
2
[24]
All these
[25]
3
high catalyst loadings, but generally produce low yields.
ral via the A coupling reaction. Therefore, one objective of
In addition, these reported technologies dealt only with the
catalytic reduction of 4-NP, and without separation and
purification of resulting products. As such, the development
of more effective heterogenous catalysts for the reduction
of nitro-substituted compounds remains an important area
of concern.
this research work was to develop a Cu-immobilized catalyst
with low metal loading (2.86 wt. %Cu) for the one-pot syn-
thesis of propargylamines from furfural at low temperature
and under solvent-free conditions. To the best of our knowl-
edge, the utilization of non-noble metals alone without suit-
able support is not effective for the reduction of 4-NP to
4-AP. So far, we have not encountered the utilization of
active support with low metal loading in the catalytic
reduction of substituted nitro-compounds. Active supports
having various functional groups that enhance catalytic
activity are expected to exhibit superior catalytic reduction
of 4-NP with NaBH4 in aqueous condition under mild
reaction conditions.
The choice of suitable supports is a significant
parameter in the design of high-performance heteroge-
neous catalysts. Recently, many types of materials that
include new inorganic supports, novel polymers, and
hybrid materials have been actively explored for the
immobilization of catalytic species. However, tedious
preparation methods and high production costs eventu-
ally prevent their widespread application. Because of
this, one of the hottest topics nowadays in the area of
heterogenous catalyst development is the utilization of
novel support materials with excellent stability and
high immobilization capacity for more facile heteroge-
neous catalysis. Carbon materials and carbonaceous
catalysts have recently gained enormous attention due
to their ease of synthesis. Some carbon-based catalysts
may in fact be prepared via one-pot synthesis. Mean-
while, the development of highly effective non-noble
metal catalysts which can significantly reduce the
catalyst loading is highly required.
Finally, we determined whether the synergistic effect
between immobilized Cu and the active carbon support
in our Cu/C catalyst is preserved over four reuse cycles
3
and observed no loss in catalytic activity in both the A
coupling and nitro-reduction reactions. This means that
our heterogenous catalyst offers a new path for catalytic
synthesis of propargylamines and the degradation of
organic pollutants.
2 | EXPERIMENTAL SECTION
2.1 | Materials
In this study, we prepared carbonized D-glucose with
para-toluenesulfonic acid (p-TSA) via a one-pot process
wherein structures embedded with the highly active
All reagents or chemicals were of laboratory grade and
[26]
–
OH, –COOH, and –SO H sites were formed.
These
were utilized without further purification. CuCl ‧2H O,
3
2
2
functional groups provide not only anchor sites
glucose, xylose, furfural, para-toluenesulfonic acid (p-TSA),
but also electronic effects that aid in catalytic
(3-aminopropyl)triethoxysilane (APTES), 4-nitrophenol
[27]
activity.
The catalyst surface was then modified with
(4-NP), dimethyl sulfoxide (DMSO), NaBH , toluene, and
4
3
-aminopropyltriethoxysilane (APTES) to produce the
ethanol were obtained from Sigma-Aldrich (Korea).
catalyst anchor sites for the immobilization of a small
amount of copper (CuCl ‧2H O in EtOH). This heteroge-
2
2
nous catalyst was evaluated for two potential applications,
namely, (i) A coupling reactions, and (ii) reduction of nitro-
2.2 | General procedure for the synthesis
of propargylamines (4aaa)
3
substituted compounds. By contrast, performing organic
conversion without the use of harmful solvents is also a pri-
mary concern in green organic synthesis. Despite wide-
spread investigations into solvent-free catalytic reactions, the
reduction of catalyst loadings in solvent-free A coupling
reactions with non-noble metal catalysts has not been
Furfural (1.04 mmol), piperidine (1.07 mmol), and
phenylacetylene (1.02 mmol) were allowed to react sol-
vent free at 80 C with 5 mg (0.0022 mmol Cu) of Cu/C
catalyst. The propargylamine (4aaa) product was isolated
by flash chromatography (ethyl acetate–hexane).
ꢀ
3

4
of 15
RATHOD ET AL.
[
30–33]
ꢀ
ꢀ
2.3 | Catalytic reduction of 4-NP (7a)
CuCl structures.
The XRD peaks at 50 and 53.3
2
represent CuO which comes from surface oxidation of
the catalyst due to exposure to moisture/air. The results
confirm that the Cu/C catalyst was successfully
synthesized.
4
-NP (0.1 g), Cu/C catalyst (3 mg; 0.0013 mmol Cu), and
ꢀ
NaBH (10 mmol) were allowed to react in H O at 25 C.
4
2
Thin-layer chromatography was used to monitor the pro-
gress of the reaction. The 4-AP (8a) product was extracted
using ethyl acetate and the solvent was removed by evap-
oration under vacuum.
The surface morphology and the chemical composi-
tion of the Cu/C catalyst were characterized by SEM–
EDX analysis. Figure 2(a–c) shows the SEM image of
morphology of the Cu/C catalyst such that Cu particles
assemble as irregular spheres on the surface of the sub-
strate. EDX analysis (Figure 2d) confirms the presence of
carbon (56.2%), oxygen (25.2%), nitrogen (5.07%), sulfur
(0.95%), silicon (3.12%), copper (5.53%), and chloride
(3.87%). The thermal stability of the synthesized Cu/C
catalyst was examined by TGA and details are presented
in the supporting information (Figure S1). The initial
3
| RESULTS AND DISCUSSION
Synthesis of biomass-derived copper catalyst (Cu/C) from
glucose is promising in terms of sustainability, availabil-
ity, cost, and ease of preparation. Furthermore, the Cu/C
catalyst consists of a carbon skeleton that is easily
separable, stable, and insoluble in most acidic/basic
aqueous environments as well as organic solvents. The
synthesized Cu/C catalyst was characterized by various
analytical techniques such as Fourier transform infrared
ꢀ
weight loss up to 100 C was ascribed to the evaporation
ꢀ
of H O. Subsequent weight loss in the 150–250 C range
2
may be ascribed to the carbonization of glucose, and fur-
ther weight loss was due to the carbonization and evapo-
[
34]
(FT-IR), X-ray diffraction (XRD), scanning electron
ration of carbon.
The next degradation step was
microscopy (SEM), SEM–energy-dispersive X-ray (EDX),
thermogravimetric analysis (TGA), X-ray photoelectron
spectroscopy (XPS), and inductively coupled plasma-mass
spectrometry (ICP-MS). Cu/C catalyst showed extraordi-
nary performance in the one-pot, multistep synthesis
allocated to the decomposition of the hydroxyl and sulfu-
ric groups and the molecular chains of APTES.
XPS was utilized to determine the surface compo-
nents of the Cu/C sample and the results are shown in
Figure 3. The Cu/C sample was prepared in KBr pellets
prior to XPS analysis. The survey spectra of Cu/C catalyst
revealed the presence of Cu2p, O1s, N1s, C1s, S2p, and
Si2p photoelectrons with binding energies 930.6, 932.6,
529.8, 399.8, 282, 166.5, and 100.0 eV, respectively, as
shown in Figure 3a. XPS peaks at 285, 529.8, and
166.5 eV correspond to C, O, and S atoms of the Cu/C
of propargylamines (4aaa) from furfural within 5 h at
ꢀ
8
0
C under solvent-free condition using only 5 mg
(0.0022 mmol Cu) of catalyst and in the selective catalytic
reduction of 4-NP using only 3 mg (0.0013 mmol Cu) of
catalyst and NaBH (10 mmol) in the presence of water
4
ꢀ
at 25 C (Scheme 2).
[
35]
The FT-IR spectra of the synthesized Cu/C catalyst is
shown in Figure 1a. The peaks at 1009 and 1100 cm−
catalyst.
The peak at 399.8 eV shown by the presence
1
of N1s confirms the immobilization of APTES on the sur-
[
36]
correspond to O=S=O stretching vibration of –SO H and
face of the Cu/C catalyst.
spond to the binding energy of Si. Copper exists in Cu
oxidation state, which was confirmed by the presence of
The peaks at 100.0 eV corre-
3
2
+
–
SO , respectively, indicating the presence of sulfonic
2
acid on the catalyst surface. The peak at 1636 and
480 cm− are attributed to C=C stretching vibrations in
1
Cu 2p and Cu 2p peaks with binding corresponding
energies of 952.6 eV and 932.6 along with their satellite
1/2
3/2
1
aromatic carbon and C–H bending vibration of alkyl
groups of terminal silanes, respectively. The peak at
peaks at 940.8 and 960.6 eV, respectively, as shown in the
018 cm− corresponds to the Si–O stretching vibration,
1
high-resolution spectra of the Cu2p region.
[37–39]
The
1
−
1
whereas the peaks at 681 and 610 cm are attributed to
the Si–O–C stretching and bending vibrations, respec-
tively, after silanization of the catalyst surface. A strong
XPS spectra also showed binding energy of 930.6 eV,
which corresponds to copper present in the metallic state
[40]
on the catalyst surface as shown in Figure 3b–f.
The
−
1
peak observed at 3425 cm , which is attributed to O–H
stretching, affirms the existence of –OH functionalities
on the catalyst surface. The XRD pattern analysis of the
as-prepared Cu/C catalyst is shown in Figure 1b. The
crystal structure and purity of the samples could be easily
obtained by XRD measurement. The Cu/C catalyst
showed the characteristic reflection for CuCl2 at
loading of Cu in the synthesized Cu/C catalyst was found
to be 2.86 wt.%, as determined by ICP-MS.
3.1 | Synthesis of propargylamines (4aaa)
from carbonyl compounds
ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
2
θ = 17 , 22 , 29 , 32 , and 39 , corresponding to the
Using the Cu/C catalyst, we investigated the mul-
ticomponent reaction of various aldehydes, amines, and
planes (220), (101), (210), (210) (111), and (200) of cubic

RATHOD ET AL.
5 of 15
SCHEME 2 Preparation of biomass-derived copper (Cu/C) catalyst
alkynes. Initially, the catalytic activity of Cu/C catalyst
was studied for the A coupling reaction of furfural
Cu/C catalyst in various other solvents (EtOH, tetrahy-
3
drofuran [THF], DMSO, and H O) product yields was
2
(
1.04
mmol),
piperidine
(1.05
mmol),
and
lower (Table 1, entries 3–6). Meanwhile, the reaction car-
ried out under solvent-free condition at 80 C for only 3 h
ꢀ
phenylacetylene (1.02 mmol) as model substrates for opti-
mizing reaction conditions such as solvent, temperature,
catalyst loading, and time (Table 1). The required product
was not obtained for the reaction without the Cu/C cata-
lyst (Table 1, entry 1). By contrast, the reaction yield
gave a high yield of 4aaa (Table 1, entry 7). Moreover,
when the amount of Cu/C catalyst added was reduced to
5 mg (0.0022 mmol Cu) under the same reaction condi-
tions, a similar product yield (91%) of 4aaa was obtained
(Table 1, entry 8). The catalytic reaction continued to
occur quantitatively when the temperature was at 90 and
reached 49% simply by using 10 mg (0.0045 mmol Cu) of
Cu/C catalyst in the presence of toluene at 80
ꢀ
C
ꢀ
(
Table 1, entry 2). The reaction product was initially
examined using gas chromatography (GC)–MS
Figure S3). Under similar reaction conditions utilizing
100 C with yields of 92% and 91%, respectively (Table 1,
entries 9 and 10). Consequently, we identified the opti-
3
(
mal
A
coupling reaction conditions using our
FIGURE 1 (a) Fourier transform infrared
spectrum of the Cu/C catalyst, and (b) X-ray
powder diffraction spectrum of the Cu/C catalyst

6
of 15
RATHOD ET AL.
FIGURE 2 Scanning electron microscopy (a–c) image of Cu/C catalyst, and (d) energy-dispersive X-ray image of the Cu/C catalyst
heterogenous catalyst to be 5 mg (0.0022 mmol Cu) of
Cu/C catalyst under solvent-free conditions at 80 C.
studied the primary amines such as aniline and
benzylamine in the solvent-free A coupling reaction. It
ꢀ
3
These results suggest that the synthesized Cu/C catalyst
provides a promising approach to the solvent-free A cou-
pling reaction at low metal loadings.
is determined in the literature that it is difficult to pro-
duce coupling products using primary amines because
primary amine typically produces imine rather than
iminium species, which are very less environment
friendly as compared with iminium species, to initiate
the further reaction with the terminal alkyne. The results
indicate that aromatic aldehyde with functional groups
3
To expand the scope of the synthesis of
propargylamines (4aaa) in solvent-free condition via the
3
A
coupling reaction, we studied various aldehydes
which were reacted with phenylacetylene and different
amines under the optimized catalytic conditions: 5 mg
such as –NO , –Cl, and –OH demonstrate good to excel-
2
(
0.0022 mmol Cu) of Cu/C catalyst loading, solvent-free
lent yield (4caa, 4daa, and 4eaa). The isolated reaction
products were analyzed by H and C nuclear magnetic
resonance (Supporting information).
ꢀ
1
13
condition, and at 80 C (Table 2). The initial investigation
of the biomass-derived furfural, with piperidine and
phenylacetylene, has been utilized as model substrate for
3
the study of A coupling reaction. Utilizing various
amines such as the cyclic (piperidine, n-methyl aniline,
diphenylamine) and acyclic (diethylamine and
diisobutylamine) secondary amines provided good yield
3.2 | One-pot synthesis of furyl-containing
propargylamines (6aaa) from xylose (5a)
(
isolated) of products (4aaa–4aea) under the reaction
Achieving one-pot synthesis of furyl-containing
propargylamines (6aaa) from xylose (5a) remains a chal-
lenge, as one has to overcome the issues related to the sep-
aration and purification of intermediates (i.e. furfural),
while saving cost, time, energy, and solvent. For the one-
pot synthesis of 6aaa from 5a, which is an important
3
solvent-free conditions. A coupling of benzaldehyde (1b)
and (piperidine) 2a, (n-methyl aniline) 2b, (aniline) 2f,
and (benzylamine) 2g with (phenylacetylene) 3a pro-
vided the corresponding coupling products (4baa, 4bba,
4
bfa, and 4bga) in excellent yields. We have additionally

RATHOD ET AL.
7 of 15
FIGURE 3 High-resolution X-ray photoelectron spectroscopy (XPS) spectra: (a) survey XPS spectra of Cu/C catalyst, and (b–f) high-
resolution XPS of C1s, O1s, Cu2p, Si2p, and S2p, respectively
component of biomass and is also inexpensive and easily
available, we initially selected xylose, piperidine, and
phenylacetylene as substrates to screen reaction condi-
tions. The results are presented in Table S1. Initially, we
have studied the effect of different solvents in the reaction
presence of 10 mg (0.0045 mmol Cu) of catalyst (Table S1,
entries 6–8). With increased Cu/C catalyst loading, the
product yield did not significantly improve (Table S1,
entry 9). However, if it was reduced from 10 to 5 mg, the
product yield decreased to 42% (Table S1, entry 10). Subse-
quently, we have optimized 10 mg (0.0045 mmol Cu) of
Cu/C catalyst in the presence of DMSO as solvent at
ꢀ
using 10 mg (0.0045 mmol Cu) of Cu/C catalyst at 100 C.
EtOH, THF, toluene, DMSO, and H O were screened,
2
ꢀ
among which DMSO provided the good yield (Table S1,
120 C, which was an ideal condition for the one-pot syn-
entries 1–5). Further, we have optimized the reaction tem-
thesis of 6aaa from 5a. The synthesis of 6aaa using 5a via
the A coupling reaction is one of the most appealing reac-
tions as it consistently involves multistep. The dehydration
o
3
perature for 6aaa formation and yields of 46% (110 C),
o
o
8
2% (120 C), and 81%(130 C) were achieved in the

8
of 15
RATHOD ET AL.
3
a
TABLE 1 Optimization of the A coupling reaction condition
ꢀ
b
S. no
Solvent (5 mL)
Toluene
Cu/C (mg)
Temp ( C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
—
10
10
10
10
10
10
5
80
80
24
24
24
24
24
24
3
—
49
Toluene
Ethanol
80
37
Tetrahydrofuran
Dimethyl sulfoxide
Water
80
12
80
43
80
Trace
92
Neat
80
Neat
80
5
91
Neat
5
90
5
92
1
0
Neat
5
100
4
91
a
Reaction conditions: furfural (1.04 mmol), piperidine (1.05 mmol), phenylacetylene (1.02 mmol), Cu/C (5 mg, 0.0022 mmol Cu), N
2
atmosphere.
b
Isolated yields.
3
of 5a to furfural is the initial step (the furfural was exam-
ined using GC–MS and high-performance liquid chroma-
tography; Figures S4 and S5), and subsequent steps
involve the reaction of furfural with a secondary amine to
produce iminium intermediate. By contrast, the Cu/C cat-
alyst can activate the terminal C–H bond of
phenylacetylene through the formation of Cu–acetylide as
an intermediate. The desired 6aaa products can be
achieved via the coupling reaction of Cu–acetylide and
isolated yield. These clearly show that the A coupling
reaction using only 10 mg (0.0045 mmol Cu) of Cu/C cat-
alyst loading is successful.
The plausible reaction mechanism is illustrated in
Scheme 3. We thus believe it should be very promising
in terms of sustainable chemistry to examine the one-
pot, multistep reaction involving 5a for the formation
of 6aaa. The one-pot synthesis of the biologically criti-
cal intermediate from 5a is also very essential aspect.
[41]
3
iminium.
However, several transformations could be
The synthesis of 6aaa using 5a via the A coupling
performed in a sequence as it avoids isolation of
intermediate.
reaction is one of the most appealing methods; besides,
it consistently involves multistep processes. The dehy-
dration of 5a to furfural is the initial step. The subse-
quent step involves the reaction of furfural with a
secondary amine to produce iminium intermediate;
meanwhile, the Cu/C catalyst can activate the terminal
C–H bond of phenylacetylene through the formation
of Cu–acetylide as an intermediate. The desired
6aaa products can be achieved via the coupling reac-
We have expanded the scope of the synthesis of 6aaa
3
from 5a via the A coupling reaction as shown in Table 3.
Dehydration of 5a to furfural involved coupling reaction
with amines and phenylacetylene to give the
corresponding furyl-containing propargylamines (6aaa,
6
aca, 6ada, and 6aca) in isolated yield as shown in
3
Table 3. A coupling of (xylose) 5a and piperidine (2a),
diphenylamine (2c) with phenylacetylene (3a) provided
the corresponding coupling products 6aaa and 6aca in
excellent yields. In addition, we have studied aliphatic
amine 2d and 2h (diethylamine and diisopropylamine,
[
42]
tion of Cu–acetylide and iminium.
Cu particles in
the synthesized biomass-derived Cu/C catalyst coordi-
nate with electronegative atom, such as the nitrogen
in the amine functionality on the surface of the
catalyst. The electron-donating character improves
the catalytic activity of copper especially in the
3
respectively) substituents that underwent the A coupling
reaction and produced products 6ada and 6aha in good

RATHOD ET AL.
9 of 15
3
a
TABLE 2 Study of substituted scope for the A coupling reaction product
a
ꢀ
Reaction conditions: furfural (1.04 mmol), piperidine (1.07 mmol), phenylacetylene (1.02 mmol), Cu/C (5 mg, 0.0022 mmol Cu), 80 C, neat,
atmosphere, isolated yields are reported.
N
2
[
43]
A3-coupling reaction.
Economical point of view,
degradation process, 4-NP can be transformed to 4-AP,
which is less toxic and can be utilized as a valuable phar-
one-pot synthesis of furyl-containing propargylamines
is highly significant.
[
25,44]
maceutical intermediate (e.g. paracetamol).
To date,
noble metals or transition metals have received much
attention for the catalytic reduction of 4-NP. However,
developing simple, low metal loading, low-cost, green
process with less hazardous catalysts having superior per-
formance for the catalytic reduction of 4-NP is still highly
demanded. In our study, we achieved the selective
catalytic reduction of 4-NP in the presence of only 3 mg
(0.0013 mmol Cu) of Cu/C catalyst and sodium borohy-
dride (10 mmol) under mild reaction conditions.
3
.3 | Catalytic reduction of 4-NP
Substituted nitro compounds are utilized in the manufac-
ture of pesticides, pharmaceutical solvents, and drugs.
Among the nitroarenes, 2-NP and 4-NP are considered
significant class of environmental pollutants by the US
Environmental Protection Agency. In the catalytic

10 of 15
RATHOD ET AL.
TABLE 3 One-pot synthesis of furyl-containing
propargylamines from xylose
shifted to 400 nm, and the reaction mixture became
bright yellow. This color change is attributed to the pro-
duction of 4-nitrophenolate ions at increased alkalinity of
the mixture (Figure 4a, c). Moreover, the peak intensity
of 4-nitrophenolate ions (400 nm) without utilizing a
Cu/C catalyst did not show any change for a long period.
This suggests that without the Cu/C catalyst, the catalytic
reduction of 4-NP did not proceed (as presented in
Figure 4b). However, when a small amount of Cu/C cata-
lyst was added into the reaction mixture, the absorbance
peak intensity at 400 nm drastically decreased and a new
absorbance peak at 305 nm gradually increased, which
can be attributed to 4-AP (Figure 4d). The catalytic reduc-
tion of 4-NP was accomplished within 100 s using the
Cu/C catalyst. After the reduction reaction, the reaction
solution becomes colorless. The reduction of 4-NP using
the Cu/C catalyst under mild optimal conditions
a
(
Figure 4e, f) exhibited a linear relationship between
ln(C /C ) and reaction time t. The reaction rate constant
t
0
calculated from the equation ln(C /C ) = k was
t
0
t
−1
0
.028 s . The catalytic reduction reaction follows the
pseudo-first-order kinetics. The rate constant (k) is calcu-
lated using the following equation
a
Reaction conditions: xylose (0.1 mmol), piperidine (1.07 mmol),
dC =d = k C or lnðC =C Þ = lnðA =A Þ = -kt
t
t
t
t
0
t
0
phenylacetylene (1.02 mmol), Cu/C 10 mg (0.0045 mmol Cu),
ꢀ
dimethyl sulfoxide (5 mL), 20 h, 120 C, N
yields are reported.
2
atmosphere, isolated
The rate constants of the samples were calculated
from the from the slope of ln(C /C ) versus time, where
t
0
3
.4 | Catalytic performances and
C refers to the absorbance at time t
and C refers to
(sec), 0
t
reduction reaction mechanism
the initial absorbance. Thus, the low-metal-loaded cata-
lyst presented superior catalytic activity for the reduction
of 4-NP to 4-AP with NaBH in the presence of H O. The
We next examined the activity of Cu/C catalyst in the
4
2
reduction of the 4-NP in the presence of NaBH as model
catalytic reduction of 4-NP utilizing the Cu/C catalyst is
an electron-transfer process. The reduction process
involved several steps (Scheme 4). In the initial process,
4-NP and BH4− diffuse from an aqueous solution to the
surface of a Cu/C catalyst via π–π stacking interactions.
4
substrate by UV–Vis spectroscopy analysis. The 4-NP
solution showed a light-yellow color and exhibited the
absorbance at 316 nm. When the reducing agent
(
NaBH ) was added into 4-NP, the absorbance peak
4
SCHEME 3 The plausible reaction mechanism for the synthesis of furyl-containing propargylamines

RATHOD ET AL.
11 of 15
4 4
FIGURE 4 UV–Visible (UV–Vis) spectra of (a) 4-nitrophenol (4-NP) before and after addition of NaBH solution, (b) 4-NP with NaBH
without the addition of any catalysts (4-nitrophenolate), (c) 4-NP before and after addition of NaBH
4
solution, and (d) time-dependent UV–
Vis absorption spectra for the catalytic reduction, (e, f) linear relationship between ln(C /C ) and reaction time t
t
0
In the subsequent step, after electron transfer from BH −
3.5 | Catalytic reduction of substituted
nitro compounds
4
and 4-NP near the Cu/C catalyst as the electron media-
−
tor, the hydrogen atoms, which are from BH , attack
4
4
-NP and reduce it. Finally, the corresponding 4-AP was
The general applicability of the Cu/C catalyst for catalytic
[45]
desorbed from the surface of the catalyst.
reduction of 4-NP with NaBH was evaluated and the
4

12 of 15
RATHOD ET AL.
SCHEME 4 A plausible mechanism for the catalytic reduction of 4-nitrophenol
best reaction condition has been screened, with results
summarized in Table 4. Initially, we examined the reac-
tion solvent (Table 4). The utilization of solvent (EtOH)
as reaction medium in the presence of 10 mg of Cu/C cat-
reaction time to 1.5 h, the catalytic reduction of 4-NP was
99% (Table 4, entries 3–6). After identifying the ideal
reaction solvent, we optimized the catalyst concentration
(Table 4, entries 7 and 8). The best reaction conditions
for the catalytic reduction of 4-NP (0.1 g) are as follows:
H O (reaction solvent), 10 mmol of NaBH , and only
alyst (0.0045 mmol Cu) achieved only 43% of 4-NP to
ꢀ
4
-AP conversion in 1 h at 25 C. This is due to the com-
2
4
ꢀ
plete insolubility of NaBH in EtOH (Table 4, entry 1).
3 mg (0.0013 mmol Cu) of catalyst at 25 C. Table 4,
entries 9 and 10 show that without utilizing a Cu/C cata-
4
When we used the biphasic solvent system with the ratio
of H O:EtOH (1:1), the conversion of 4-NP increased to
lyst and in the absence of NaBH , the catalytic reduction
2
4
6
5% in 1 h (Table 4, entry 2). Moreover, using THF and
reaction did not show any conversion. The excellent per-
formance of the synthesized Cu/C catalyst can be attrib-
uted to the following reasons: first, the electron-rich
amino groups act as an electron donor to enrich the elec-
tron of the Cu species on the catalyst, and second, the
MeOH solvent as the reaction medium, the catalytic
reduction of 4-NP was 3.5% and 29%, respectively, in 1 h.
It can be seen that when utilizing only H O as the sol-
2
vent, the conversion was 79% in 1 h. By increasing the
a
TABLE 4 Optimization of the 4-nitrophenol reduction reaction
b
b
S. no
Cu/C (mg)
Solvents (5 mL)
Ethanol
Time (h)
Yield (%)
Selectivity (%)
1
2
3
4
5
6
7
8
10
10
10
10
10
10
5
1
43
65
79
3.5
29
99
99
99
—
—
100
100
100
100
100
100
100
100
—
Ethanol/Water
Water
1
1
Tetrahydrofuran
Methanol
Water
1
1
1.5
2
Water
3
Water
2
9
—
3
Water
1
c
1
0
Water
1
—
a
4 2
Reaction conditions: 4-nitrophenol (0.1 g), Cu/C (3 mg, 0.0013 mmol Cu), NaBH (10 mmol), H O (10 mL), room temperature.
Isolated yields.
b
c
Without NaBH4.

RATHOD ET AL.
13 of 15
4
-NP is likely to adsorb on the Cu/C catalyst with rich
functional groups have strong coordination of copper spe-
cies that have a positive effect on the surface of the cata-
electron density as a result of its strong electron-
withdrawing properties. Consequently, outstanding selec-
tivity could be attained.
[
47]
lyst.
Furthermore, when dispersed in water, catalyst
[46]
surface becomes highly negatively charged as a result of
ionization of phenolic hydroxyl groups, sulfuric acid,
carboxylic acid, and amine on the Cu/C catalyst sheets.
Because of the electron-donating character, the catalytic
activity of copper is improved, especially in the catalytic
To expand the scope of Cu/C catalyst application for
substituted nitro compounds reduction (Table 5), the
reduction of 2-NP utilizing the catalyst was also evalu-
ated. A lower yield compared with the catalytic reduction
of 4-NP at room temperature (8a, 8b) was achieved. Fur-
thermore, for the catalytic reduction of 3-nitrotoluene
and 4-nitrotoluene, no demethylation was observed, with
achieved yields of 92% and 96%, respectively, at room
[
48]
reduction of 4-NP.
The significance of electron-
donating support groups offer a promising approach for
[27]
attractive catalytic performance in other reactions.
A
comparative study of the reported synthesis of
propargylamines and reduction of 4-NP is summarized
in Table S2. These results clearly suggest that the
Cu/C catalyst is extremely active for the synthesis
of propargylamines and catalytic reduction of
4-NP. Recycling experiments for the synthesis of
propargylamines (4aaa) from furfural and reduction
of 4-NP using Cu/C catalyst were conducted under the
aforesaid optimal condition. After the completion of reac-
tions, Cu/C catalyst can be recovered using filtration,
followed by washing with EtOH and drying in vacuum at
temperature and without affecting the C–CH bond (8c
3
and 8d). Moreover, for 4-nitroaniline, the catalytic reduc-
tion reaction was complete in 6 h (8e). The Cu/C catalyst
was extremely active for the reduction of substituted nitro
compounds while functional groups such as –CH , –OH,
and –NH were not affected. Furthermore, it is worth
noting that selective reduction of a nitro compound hav-
ing halogen functionalities (Cl) with good yield was suc-
cessfully achieved under optimal reaction conditions (8f).
The nitrobenzene reduction in the presence of catalyst
3
2
ꢀ
ꢀ
gave a yield of 94% at 25 C in 5 h (8g). All these nitro-
60 C. Then, the catalyst was directly used in the next
substituted compounds were reduced in the presence of
Cu/C catalyst (3 mg, 0.0013 mmol Cu) with excellent
yields and afforded highly selective products. Synthesized
biomass-derived Cu/C catalysts having electron-donating
run as presented in Figure 5. We also performed XRD
characterization of the Cu/C catalyst after the fourth
cycle. As seen from Figure S2, whereas the intensity of
a
TABLE 5 Substrate scope for the reduction of nitroarenes
a
Reaction conditions: 4-nitrophenol (0.1 g), Cu/C (3 mg,
0
.0013 mmol Cu), H
2
O (10 mL), NaBH
4
(10 mmol), room tempera-
FIGURE 5 Catalytic reusability study of the Cu/C catalyst for
the A coupling reaction and catalytic reduction of 4-nitrophenol
3
ture, isolated yields reported with 100% selectivity.
Abbreviation: RT, room temperature.
(4-NP) under optimal conditions

14 of 15
RATHOD ET AL.
some peaks was reduced, the crystal structure of the cata-
lyst remained intact, which confirms its stability even
after four cycles.
ORCID
Hern Kim https://orcid.org/0000-0002-0467-7137
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