Visible Light-Driven Efficient Synthesis of Amides from Alcohols using Cu?N?TiO2 Heterogeneous Photocatalyst

Article abstract of DOI:10.1002/ejoc.202001466

Amides were synthesized from alcohols and amines in high yields using an in situ generated active ester of N-hydroxyimide with our developed Cu?N?TiO₂ catalyst at room temperature using oxygen as a sole oxidant under visible light. The catalyst can be easily prepared, robust, and recycled four times without a considerable change in catalytic activity. This developed protocol applies to a wide substrate scope and has good functional group tolerance. The application of this amidation reaction has been successfully demonstrated for the synthesis of moclobemide, an antidepressant drug, and an analog of the itopride drug on a gram scale.

Full text of DOI:10.1002/ejoc.202001466

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doi.org/10.1002/ejoc.202001466
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Visible Light-Driven Efficient Synthesis of Amides from
Alcohols using CuÀ NÀ TiO Heterogeneous Photocatalyst
2
[a, b]
[a, b]
[a, b]
Krishnadipti Singha,
Subhash Chandra Ghosh,*
and Asit Baran Panda*
Amides were synthesized from alcohols and amines in high
yields using an in situ generated active ester of N-hydroxyimide
protocol applies to a wide substrate scope and has good
functional group tolerance. The application of this amidation
reaction has been successfully demonstrated for the synthesis
of moclobemide, an antidepressant drug, and an analog of the
itopride drug on a gram scale.
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with our developed CuÀ NÀ TiO catalyst at room temperature
2
using oxygen as a sole oxidant under visible light. The catalyst
can be easily prepared, robust, and recycled four times without
a considerable change in catalytic activity. This developed
Introduction
lated in recent years, as such reactions proceed smoothly at
[15–16]
room temperature (RT).
Recently we have reported N-
The amide derivatives are the most important class of
compounds found in natural products, pharmaceutical com-
doped TiO catalyst for the synthesis of N-hydroxyimide active
2
ester from alcohol using two equivalent of sacrificial TBHP as an
[1]
[17]
pounds, and synthetic polymers. More than 25% of commer-
external oxidant. A similar strategy was reported by Xie and
[2]
[18a]
cial drugs contain an amide group. In general, amide bonds
are synthesized by the reaction between activated forms of
carboxylic acids and amines, and/or by using a coupling
Yu groups for Iodide-catalyzed amide synthesis
catalyzed esterification
and Iron
[18b]
via the N-hydroxyimide active ester
route. Although the substrate scope of the reactions has wide
under moderately mild conditions, the most critical disadvant-
age of the reaction was the use of super stoichiometric
amounts of TBHP in decane and longer reaction time (24 h).
This aspect has led us to the development of a new catalyst for
the amidation of alcohols under mild reaction conditions and
with good substrate scope. Based on the proposed mechanism,
the role of TBHP is to accelerate the rate of selective oxidation
of alcohol to aldehyde. We have envisioned that the loading of
copper in our catalyst can do a similar job, ease the oxidation of
alcohol under the aerobic condition in the presence of a
photocatalyst. In continuation of our effort, herein we report
[3]
reagent. The synthesis of amides directly from alcohol is
highly desirable, it affords a high atom and cost economical
[
4]
st
synthetic route. In 2007, Milstein and co-workers 1 reported
environmentally benign direct amidation of alcohols and
[5]
amines using the ruthenium PNN pincer complex as a catalyst.
Since then several groups have reported the direct synthesis of
[6]
[7]
amides from alcohols mainly using, homogeneous Ru, Rh,
[
8]
[9]
[10],
[11]
Ir, Fe, Cu,
and other transition metal catalysts.
Sup-
[
12]
[13]
[14]
ported Ag,
Au,
and heterogeneous Mn
catalyst also
reported for amidation of alcohol. These methods have the
advantages of environmentally benign and atom efficiency
from the traditional acid chloride or coupling reagents-based
amide bond synthesis. However, most of the reactions need an
elevated temperature and problem associated with TM-catalyst
contamination in the desired product. Towards sustainable
development, visible-light-mediated organic synthesis, and
energy-efficient reactions at ambient conditions are challenging
our developed heterogeneous photocatalyst CuÀ NÀ TiO under
2
very mild conditions for the synthesis of amides from alcohols
and amines under 40w CFL light source using oxygen as sole
oxidant and short reaction time at room temperature.
[
15]
tasks and highly desirable.
Sunlight (visible light), prime Results and Discussion
sustainable energy resources on earth, driven reactions (photo-
catalysis), i.e., conversion of solar energy to chemical energy,
using reusable heterogeneous photocatalyst, has been stimu-
XRD pattern of the CuÀ NÀ TiO catalyst evidenced the presence
2
of all the peaks of anatase TiO . In addition to all the peaks of
2
anatase TiO2 two additional peaks at 2θ=43.3° and 50.6°,
ascribed to the (111) and (200) planes of metallic Cu, was also
observed and confirmed the successful incorporation of metallic
Cu in the catalyst system (Figure 1a). The calculated crystallite
size of CuÀ NÀ TiO is almost equivalent to that of bare NÀ TiO .
[a] K. Singha, Dr. S. C. Ghosh, A. B. Panda
CSIR-Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI)
GB Marg, Bhavnagar-364002, Gujarat, India
E-mail: scghosh@csmcri.res.in
2
2
abpanda@csmcri.org
The results imply that the structure of bare NÀ TiO remains
2
https://subhashghosh.wixsite.com/scghoshgroup
https://abpandasgroup.webs.com/
b] K. Singha, Dr. S. C. Ghosh, A. B. Panda
Academy of Scientific and Innovative Research (AcSIR),
Ghaziabad 201002, India
unaltered during Cu impregnation. A low magnified TEM image
[
of CuÀ NÀ TiO showed the presence of 2D sheet assembled
2
spheres, similar to that of bare NÀ TiO (Figure S1). Magnified,
2
indicate the presence of some foreign particles, in the size
range of 1–4 nm, in the surface of the 2D sheet (Figure 1b),
Supporting information for this article is available on the WWW under
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a distinct Cu-LMM peak at 568.2 eV was identified (Figure S3).
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Thus, XPS spectra confirmed the CuÀ NÀ TiO catalyst contains
2
0
2+
2+
both Cu and Cu and the existence of Cu is due to the
aerial surface oxidation of metallic Cu during catalyst collection
and storage. In the UV-Vis diffuse reflectance spectra (DRS) of
CuÀ NÀ TiO , a reasonable improvement in the absorption of
2
light in the visible region to that of bare NÀ TiO (Figure 1e).
2
Visible light absorption efficiency is increased incorporation of
metallic Cu nanoparticles in the NÀ TiO system (CuÀ NÀ TiO ),
2
2
which can be ascribed to the Surface Plasmon Resonance peak
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[20]
of plasmonic Cu NPs.
Pl spectra evidenced a reasonable
reduction of peak intensity for CuÀ NÀ TiO to that of NÀ TiO
2
2
(
Figure 1f). This is due to the migration of photo-generated
electrons in CB of NÀ TiO to Cu and restricts recombination.
2
Figure 1. (a) XRD pattern of synthesized bare and Cu impregnated NÀ TiO
2
hollow sphere; (b) TEM and (c) HR-TEM images of the synthesized Cu
Photocatalytic reactions
impregnated NÀ TiO
2
hollow sphere; (d) Core level Cu2p XPS; (e) UV-Vis. DRS
and (f) PL spectra of synthesized bare and Cu impregnated NÀ TiO
2
hollow
sphere.
After successful synthesis and full characterization of the
CuÀ NÀ TiO catalyst in hand, we next explored the catalytic
2
activity. The reaction of 4-chlorobenzyl alcohol 1a with 2-
phenylethylamine 3a in presence of N-hydroxyphthalimide 2a
was taken as a model substrate to optimize the reaction
condition under the irradiation of light from a 40 W CFL lamp
and at ambient condition (Table 1). In first consideration, we
which was absent in the bare NÀ TiO (Figure S1). The foreign
2
particles are most probably metallic Cu nanoparticles. Further
through investigation of respective HRTEM images, evidenced
that presence of distinct lattice fringes in sheets and parties
with inter planner distance of 0.23, ascribed to (001) plane of
have used our synthesized 5 wt% Cu loaded TiO catalyst on
2
anatase TiO , and can be 0.21 nm, ascribed to the (111) plane of
the amidation reaction in acetonitrile solvent, to our delight as
envisioned our catalyst showed excellent reactivity, and 91% of
2
metallic Cu, respectively (Figure 1c). HRTEM images confirmed
the presence of crystalline Cu nanoparticles on the surface of
the 2D NÀ TiO sheet. N2 adsorption-desorption isotherm of
2
CuÀ NÀ TiO catalyst corresponds to type IV (Figure S2), typically
2
[
a]
[17]
Table 1. Reaction optimization.
which is similar to that of bare NÀ TiO . The calculated total
2
BET surface area and average pore size of CuÀ NÀ TiO are
2
2
À 1
1
74 m g and 6.5 nm, respectively. Although with respect to
the bare NÀ TiO no significant change in pore size distribution
2
for CuÀ NÀ TiO took place, a reasonable enhancement of the
2
2
À 1
2
À 1
total surface area, from 155 m g to 174 m g was observed,
most probably due to the contribution from the metallic Cu
Catalyst
Oxidant
O2
Solvent
T
Y
[%]
[
h]
nanoparticles on the surface of TiO sheets. Wide survey XPS
1
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9
1
5 wt% CuÀ NÀ TiO (15 mg)
CH CN
8
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8
16
16
91
65
93
40
75
92
trace
trace
87
2
2
3
2.5 wt% CuÀ NÀ TiO
2
(15 mg)
O
2
CH
3
CN
spectra of CuÀ NÀ TiO evidenced the presence of Ti, O, Cu, and
2
10 wt% CuÀ NÀ TiO (15 mg)
2
O2
CH CN
3
more importantly the N (Figure S3). Corresponding, high-
resolution Ti2p spectra showed the presence of two peaks at
5 wt% CuÀ NÀ TiO
2
(5 mg)
O
2
CH
3
CN
5 wt% CuÀ NÀ TiO (10 mg)
2
O2
CH CN
3
5 wt% CuÀ NÀ TiO
2
(20 mg)
O
2
CH
3
CN
4
64.8 and 459.1 eV, ascribed to the Ti2p1/2 and Ti2p3/2,
5 wt% CuÀ NÀ TiO (15 mg)
2
H O2
2
CH CN
3
4
+
respectively, and confirm the presence of Ti
as TiO2.
5 wt% CuÀ NÀ TiO
2
(15 mg)
DTBP
TBHP
CH
3
CN
Deconvoluated N1s spectra demonstrated the presence of two
5 wt% CuÀ NÀ TiO (15 mg)
CH CN
2
3
0
NÀ TiO
2
(15 mg)
O
2
CH
3
CN
20
peaks at 398.08 and 399.11 eV, corresponds to the OÀ TiÀ N and
11
5 wt% CuÀ NÀ TiO
5 wt% CuÀ NÀ TiO
5 wt% CuÀ NÀ TiO
5 wt% CuÀ NÀ TiO
5 wt% CuÀ NÀ TiO
5 wt% CuÀ NÀ TiO
2
2
2
2
2
2
O2
DMF
DCM
EtOH
BTF
trace
trace
trace
trace
oxidized TiÀ OÀ N species as substitutional N of TiO , respectively
2
12
O
2
[19]
(
Figure S3). All the above-mentioned results are quite identi-
13
O2
14
O
2
cal to that of bare NÀ TiO and indicate that the doped nitrogen
2
[b]
15
O2
CH CN
3
89
[c]
of bare NÀ TiO remains intact even after Cu impregnation. The
2
16
O
2
CH
3
CN
ND
Cu 2p (Figure 1d) spectra evidenced the presence of peaks at
[a] Reaction condition: Unless otherwise specified, all the optimization
reactions were carried out with 4-chlorobenzyl alcohol 1a (0.4 mmol,
1.0 equiv), N-hydroxyphthalimide 2a (0.48 mmol, 1.2 equiv), 2 ml solvent,
0
1+
9
9
30.7 and 951.6 eV, ascribed to either Cu or Cu , and peaks at
33.06 and 953.3 eV beside with spin splitting originated
2
+
1
5 mg catalyst, under the irradiation of light from 40 W CFL lamp, at
ambient condition for 6 h then 2-phenylethylamine 3a (0.6 mmol,
.5 equiv.) was added and stirred for additional 15 min; b] reaction carried
separately at around 961.11 eV, recognized as Cu . Two intense
peaks in the range of 938–942 eV, identified as satellite peaks of
Cu , were also identified. Here it is essential to mention that
1
2
+
out under the irradiation of light from a blue LED. [c] reaction carried out
under dark.
0
the recognized peaks at 930.7 and 951.6 eV are for only Cu , as
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the desired 4-chloro-N-phenethylbenzamide product was ob-
served (Table 1, entry 1). Next, we have checked the amount of
position of phenyl ring reacts with 2-phenyl amine and gave
the desired sec-amide in good to excellent yields (up to 91%,
entries 5b–5d), halide substituted (weak electron-withdrawing)
chloro and bromo derivatives gave excellent yields (91% and
89% respectively, entries 5a, and 5e). Whereas strong electron-
withdrawing groups such as fluoro, nitrile, and nitro proceeded
will with slightly less yield (70–72%, entries 5f–5g). These
results indicate the electronic effect is not so significant. Ortho-
substituted benzyl alcohols, which might have some steric
hindrance are also effective for tandem amidation (entries 5i–
5j) gave the desired sec-amide in good yields. Next, we check,
other aryl and heteroaryl methyl alcohols as a substrate,
naphthalene, furan, pyridine, and thiophene derivatives with 2-
phenylethylamine proceed well to produce the sec-amide in
good yields (entries 5k–5n). Other primary amines such as
benzylamine and n-butyl amines were also worked well with 2-
thiophene methanol and gave the desired product in very good
yield (70%, 5o; 73%, 5p). To our delight, secondary amines
such as pyrrolidine and diethylamine were also worked well
and gave the desired tert-amide in very good yields (5q, 67%;
5r, 68%, 5u, 82% and 5v, 87%). Aliphatic alcohol, 3-Phenyl-1-
propanol reacted with 2-Phenethylamine and gave the desired
amide in moderate yield (5w, 40%), highlighting that reaction
is not limited to benzylic alcohols. On a gram scale, tandem
amidation of 4-chloro benzyl alcohol with morpholinoethan-
amine gave 76% of moclobemide (5x), a generic drug used for
the treatment of depression. An analog of the itopride drug
molecule was easily synthesized with good yield in gram scale
65% (5y), itopride is used in the treatment of gastrointestinal
(GI) symptoms (Scheme 1).
To get some insight into the reaction mechanism, we have
carried out some control experiments. First, we carried out the
reaction in presence of radical scavengers like TEMPO [(2,2,6,6-
Tetramethylpiperidin-1-yl)oxyl] and BHT (butylated hydroxyl
toluene) which completely inhibited the reaction (Scheme 2).
These results indicate the reaction might proceed through a
radical mechanism i.e. SET (single electron transfer) process. To
understand the role of visible light we have performed the light
on-off studies, at the beginning for 30 min, the light was on
after that for every 1 h we have turned off the light and
subsequently turned it on and check the reaction progress by
HPLC (Figure 3). It was observed that in absence of light no
progress in the reaction and upon light on condition reaction
again re-started, which indicates the reaction is photocatalytic.
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copper loading on NÀ TiO , 2.5% wt% CuÀ NÀ TiO showed little
2
2
diminished activity (65%, entry 2) and 10% CuÀ NÀ TiO catalyst
2
showed similar reactivity (93%, entry 3). The amount of catalyst
found to be critical, 5 mg and 10 mg catalyst have inferior
results (40%, and 75%, entries 4–5 respectively), and 20 mg
catalyst showed a similar result (92%, entry 6). The addition of
hydrogen peroxide and DTBP as an external oxidant (2 equiv)
found to be ineffective completely inhibits the reaction (entries
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
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–8), whereas TBHP as an oxidant gave a similar result (89%,
entry 9). Simple NÀ TiO gave a lower yield (20%, entry 10),
2
which indicates the copper loading on TiO2 is critical. Next, a
screening of solvents was carried out and found DMF, DCE,
ethanol, and BTF are ineffective, no product was observed
(
entries 11–14), so the solvent choice is critical and acetonitrile
found to be superior. When we carried out the reaction with
W blue LED light, a similar yield was observed (entry 15)
3
Finally, when carried out the reaction at dark even after 16 h no
product formation was observed (entry 16), indicates the
necessity of light and photocatalysis pathway of the reaction. It
is noteworthy that the addition of amine from the beginning
gives the lower yield of the desired amide, and in an absence of
NHPI, no amidation product was observed. To get a better
understanding of the reaction profile, the conversion of 4-
chlorobenzyl alcohol (1a) with NHPI (2a) was monitored with
time and found the formation of an active ester is completed
within 6 h (Figure 2). After 6 h, upon the addition of 2-phenyl-
ethylamine, amidation was very fast, within 15 min reaction was
completed to get the desired amide (5a) product with a 91%
yield.
With the optimization condition in hand (Table 1, entry 1),
the scope and limitation of this tandem amidation reaction
were then explored with various alcohols and amines. In
general, most of the reaction proceeds well and gave the
desired amide in good yields as shown in Table 2. Several
benzyl alcohols with electron-donating substituted in the para
Figure 2. Reaction progress monitored by HPLC: reaction of the alcohol with
NHPI to active ester.
Scheme 1. Synthetic application, gram-scale synthesis of moclobemide, and
itropide in one pot.
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[a]
Table 2. The substrate scope of amidation reaction.
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[
a] Reaction conditions: A reaction tube containing a solution of benzyl alcohol 1 (0.4 mmol), N-hydroxyphthalimide 2a (0.48 mmol, 1.2 equiv), 15 mg
catalyst, in acetonitrile (2 mL) was stirred under the irradiation of light from 40 W CFL lamp, at ambient condition for 6 h; then amine 3 (0.6 mmol, 1.5 equiv.)
was added and stirred for additional 15 min.
Figure 3. Light on-off experiment.
Scheme 2. Radical inhibition study.
Our catalyst showed very good recyclability, after comple-
tion of the reaction catalyst was filtered, washed and dried, and
reused (Figure 4). Further, the hot filtration test confirmed the
heterogeneity of the reaction. We monitored the reaction
progress after taking out the reaction mixture via cannula from
the solid catalyst, No further reaction was observed, in the
solution part, which suggests that the active catalyst was not
leached out to the solution and the reaction is heterogeneous
in nature. ICP-AES analysis of the filtrate of the standard
reaction also tested after completion of the reaction, a
negligible amount of Cu (3 ppm and 5 ppm) leached in the
filtrate for both the second and fourth cycle respectively.
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LET ALMECA XR) with a 532 nm laser beam, ESCALAB 250 XPS
System with a monochromatic Al Kα (150 W) source, Horiba Jobin
spectrophotometer.
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Acknowledgments
CSIR-CSMCRI Communication No 142/2020. We are thankful to
the SERB, DST, India [CRG/2019/000205, and EMR/2016/002427]
for financial support for this work. The authors also acknowledge
the AESD&CIF of CSIR-CSMCRI for constant analytical support. KS
is thankful to CSIR for his fellowship.
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Figure 4. Recyclability of the catalyst for standard amidation (5a).
Conflict of Interest
Conclusion
The authors declare no conflict of interest.
In conclusion, we have developed an efficient and reusable
heterogeneous CuÀ NÀ TiO hollow sphere with superior visible-
2
Keywords: Amidation · Cu loaded NÀ TiO · Heterogeneous ·
2
light absorption efficiency for the synthesis of amides starting
from alcohol and amine at room temperature. The synthesized
CuÀ NÀ TiO2 hollow sphere showed excellent photocatalytic
activity. The applicability of the method is further showcased by
the gram-scale synthesis of drug or drug analogs such as
moclobemide and itropide. The catalyst is reused for 4 times
without significant loss of reactivity. Compared with previous
reports, our catalyst is effective at room temperature, no need
for an inert atmosphere, good functional group tolerance, and
recyclable.
Photocatalysis · Visible light
[
[
1] a) J. M. Humphrey, A. R. Chamberlin, Chem. Rev. 1997, 97, 2243–2266;
b) V. R. Pattabiraman, J. W. Bode, Nature 2011, 480, 471–479; c) T.
Cupido, J. Tulla-Puche, J. Spengler, F. Albericio, Curr. Opin. Drug
Discovery Dev. 2007, 10, 768–783.
2] a) J. R. Dunetz, J. Magano, G. A. Weisenburger, Org. Process Res. Dev.
2016, 20, 140–177; b) J. S. Carey, D. Laffan, C. Thomson, M. T. Williams,
Org. Biomol. Chem. 2006, 4, 2337–2347.
[3] E. Valeur, M. Bradley, Chem. Soc. Rev. 2009, 38, 606–631.
[
4] a) C. Gunanathan, D. Milstein, Chem. Rev. 2014, 114, 12024–12087;
b) G. E. Dobereiner, R. H. Crabtree, Chem. Rev. 2010, 110, 681–703; c) C.
Chen, S. H. Hong, Org. Biomol. Chem. 2011, 9, 20–26.
[5] C. Gunanathan, Y. Ben-David, D. Milstein*, Science 2007, 317, 790–792.
6] a) L. U. Nordstrøm, H. Vogt, R. Madsen, J. Am. Chem. Soc. 2008, 130,
7672–17673; b) S. C. Ghosh, S. Muthaiah, Y. Zhang, X. Xu, S. H. Hong,
Experimental Section
[
1
For the synthesis of CuÀ NÀ TiO
, the first sheet mediated NÀ TiO
2
2
Adv. Synth. Catal. 2009, 351, 2643–2649; c) A. J. A. Watson, A. C. Maxwell,
J. M. J. Williams, Org. Lett. 2009, 11, 2667–2670; d) S. Muthaiah, S. C.
Ghosh, J. E. Jee, C. Chen, J. Zhang, S. H. Hong, J. Org. Chem. 2010, 75,
hollow spheres were synthesized, and then the metallic Cu was
impregnated on it.
3
002–3006; e) T. Higuchi, R. Tagawa, A. Iimuro, S. Akiyama, H. Nagae, K.
Synthesis of sheet mediated NÀ TiO
hollow spheres. It was
synthesized following our previously reported method. In a typical
2
Mashima, Chem. Eur. J. 2017, 23, 12795–12804.
[7] a) K. Fujita, Y. Takahashi, M. Owaki, K. Yamamoto, R. Yamaguchi, Org.
Lett. 2004, 6, 2785–2788; b) T. T. Nguyen, K. L. Hull, ACS Catal. 2016, 6,
8214–8218.
[8] O. Saidi, M. J. Bamford, A. J. Blacker, J. Lynch, S. P. Marsden, P. Plucinski,
R. J. Watson, J. M. J. Williams, Tetrahedron Lett. 2010, 51, 5804–5806.
synthetic procedure, 30 mL NH OH (30%) solution was added to a
4
30 ml titanium peroxy-carbonate solution, from 3 ml titanium
isopropoxide, was added under constant stirring. Then by adding
deionized water, the total of the solution was made up to 90 ml.
33 ml of this solution mixture was taken in 50 ml Teflon lined
stainless steel autoclave. After proper sealing, the autoclave was
transferred to a pre-heated oven at 120°C for 18 h. Finally, the
obtained precipitate was collected after proper washing with de-
ionized water followed by ethanol and drying and calcined at
[
9] a) M. Arefi, D. Saberi, M. Karimi, A. Heydari, ACS Comb. Sci. 2015, 17,
41–347; b) S. C. Ghosh, J. S. Y. Ngiam, A. M. Seayad, D. T. Tuan, C. W.
Johannes, A. Chen, Tetrahedron Lett. 2013, 54, 4922–4925.
[10] a) J. Gu, Z. Fang, Y. Yang, Z. Yang, L. Wan, X. Li, P. Wei, K. Guo, RSC Adv.
016, 6, 89413–89416; b) P. E. Piszel, A. Vasilopoulos, S. S. Stahl, Angew.
3
2
Chem. Int. Ed. 2019, 58, 12211–12215.
4
00°C for 2 h.
[11] Y. F. Guo, T. L. Ren, B. H. Xu, Y. F. Wang, S. J. Zhang, Asian J. Org. Chem.
2016, 5, 568–574.
Metallic Cu impregnation on NÀ TiO : First the calcined NÀ TiO was
[12] K. Shimizu, K. Ohshima, A. Satsuma, Chem. Eur. J. 2009, 15, 9977–9980.
[13] a) Y. Wang, D. Zhu, L. Tang, S. Wang, Z. Wang, Angew. Chem. Int. Ed.
2011, 50, 8917–8921; b) J. F. Soulé, H. Miyamura, S. Kobayashi, J. Am.
Chem. Soc. 2011, 133, 46, 18550–18553; c) L. Zhang, W. Wang, A. Wang,
Y. Cui, X. Yang, Y. Huang, X. Liu, W. Liu, J. Y. Son, H. Oji, T. Zhang Green,
Chem., 2013,15, 2680–2684.
2
2
dispersed in methanol-water and to it required amount of freshly
prepared methanolic Cu(OAc) .H O solution was added dropwise
2
2
with stirring. To that solution, hydrazine hydrate solution was
added dropwise and stirred the whole solution for an additional
2 h. Finally, the precipitate was collected by washing with de-
ionized water followed by ethanol and dried the precipitate at 70°C
for 12 h.
[
14] K. Yamaguchi, H. Kobayashi, T. Oishi, N. Mizuno, Angew. Chem. Int. Ed.
2012, 51, 544–547.
[
15] a) X. Lang, X. Chen, J. Zhao, Chem. Soc. Rev. 2014, 43, 473–486; b) Sk. S.
Shah, M. Shee, Y. Venkatesh, A. K. Singh, S. Samanta, N. D. P. Singh,
Chem. Eur. J. 2020, 26, 3703–3708.
Characterizations. The following instruments were used for Charac-
terization: Miniflex-II (FD 41521) powder diffractometer (Rigaku,
Japan), JEOL JEM 2100 transmission electron microscope (TEM),
Shimadzu UV-2550 spectrophotometer, Raman spectrometer (NICO-
[16] a) J. Chen, J. Cen, X. Xu, X. Li, Catal. Sci. Technol. 2016, 6, 349–362;
b) J. L. White, M. F. Baruch, J. E. Pander Iii, Y. Hu, I. C. Fortmeyer, J. E.
Park, T. Zhang, K. Liao, J. Gu, Y. Yan, T. W. Shaw, E. Abelev, A. B. Bocarsly,
Eur. J. Org. Chem. 2021, 657–662
www.eurjoc.org
661
© 2020 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001466
Chem. Rev. 2015, 115, 12888–12935; c) S. K. Pahari, P. Pal, D. N.
D. He, J. Phys. Chem. C 2007, 111, 10618–10623; c) F. Wang, X. He, L.
Sun, J. Chen, X. Wang, J. Xu, X. Han, J. Mater. Chem. A. 2018, 6, 2091–
2099; d) C. Zhang, Y. Zhou, J. Bao, X. Sheng, J. Fang, S. Zhao, Y. Zhang,
W. Chen, ACS Appl. Mater. Interfaces 2018, 10, 18796–18804.
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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7
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9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
Srivastava, S. Ghosh, A. B. Panda, Chem. Commun. 2015, 51, 10322–
10325; d) R. Vadakkekara, A. K. Biswas, T. Sahoo, P. Pal, B. Ganguly, S. C.
Ghosh, A. B. Panda, Chem. Asian J. 2016, 11, 3084–3089; e) K. Singha, A.
Mondal, S. C. Ghosh, A. B. Panda, Chem. Asian J. 2018, 13, 255–260; f) Q.
Liu, L.-Z. Wu, Natl. Sci. Rev. 2017, 4, 359–380.
[20] P. Zhang, T. Song, T. Wang, H. Zeng, RSC Adv. 2017, 7, 17873–17881.
[17] K. Singha, S. C. Ghosh, A. B. Panda, Chem. Asian J. 2019, 14, 3205–3212.
[
18] a) G. Wang, Q. Y. Yu, J. Wang, S. Wang, S. Y. Chen, X. Q. Yu, RSC Adv.
013, 3, 21306–21310; b) X. Xu, J. Sun, Y. Lin, J. Cheng, P. Li, X. Jiang, R.
Bai, Y. Xie, Eur. J. Org. Chem. 2017, 7160–7166.
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Manuscript received: November 9, 2020
Revised manuscript received: December 8, 2020
Accepted manuscript online: December 9, 2020
[19] a) S. Sun, P. Gao, Y. Yang, P. Yang, Y. Chen, Y. Wang, ACS Appl. Mater.
Interfaces. 2016, 8, 18126–18131; b) Y. Cong, J. Zhang, F. Chen, M. Anpo,
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