CuO nanoparticles supported on silica: A simple, efficient, and recyclable catalyst for hydroacylation reactions of aldehydes with azodicarboxylate

Article abstract of DOI:10.1246/cl.2012.1484

We describe a green and efficient procedure for the hydroacylation of aldehydes with diisopropyl azodicarboxylate, using CuO nanoparticles supported on silica (CuO-np/SiO₂) as a catalyst, in good to excellent yields. A wide range of aldehydes,

Full text of DOI:10.1246/cl.2012.1484

doi:10.1246/cl.2012.1484
1484
Published on the web November 10, 2012
CuO Nanoparticles Supported on Silica: A Simple, Efficient, and Recyclable Catalyst
for Hydroacylation Reactions of Aldehydes with Azodicarboxylate
Suleman M. Inamdar,1,2 Vinod K. More,2 and Sisir K. Mandal*3
1Chemical Engineering and Process Development Division, National Chemical Laboratory,
Dr. Homi Bhabha Road, Pune-411 008, India
2Aditya Birla Science and Technology Centre, Plot No. 1 and 1-A/1, MIDC Taloja,
Panvel, Navi Mumbai-410 208, India
3Technology Platform Department, Asian Paints R and T Centre, Plot No. C3-B/1, TTC Industrial Area,
Pawane, Thane Belapur Road, Navi Mumbai-400 705, India
(Received June 28, 2012; CL-120695; E-mail: sisir.mandal@asianpaints.com)
We describe a green and efficient procedure for the
nanoparticles supported on silica17 (Scheme 1). The factors
affecting the reactions are also discussed.
hydroacylation of aldehydes with diisopropyl azodicarboxylate,
using CuO nanoparticles supported on silica (CuO-np/SiO2) as a
catalyst, in good to excellent yields. A wide range of aldehydes,
including aromatic and aliphatic compounds, were considered.
The catalyst is found to be truly heterogeneous in the reaction
mixture and can be reused without loss of catalytic activity.
Hydroacylation reactions between benzaldehyde and diiso-
propyl azodicarboxylate were studied, using CuO nanoparticles
supported on silica as a catalyst, at a temperature of 60 °C, using
different solvents. The catalyst requires no ligands and additives
to accelerate the reaction, which is an added advantage in
making the process clean. The pertinent data are presented in
Table 3. The yield of the reaction varies in the range 60-95%,
depending on the substrate and conditions used for the reaction.
The CuO-np/SiO2 catalyst was prepared as described in the
literature.18 The catalyst was characterized by powder X-ray
diffraction, transmission electron microscopy, and atomic
absorption spectroscopy (see the Supporting Information).19
First, we studied the effect of the solvent on the hydro-
acylation reaction between benzaldehyde and diisopropyl
azodicarboxylate. Remarkably, acetonitrile gave the hydroacy-
lation product smoothly in good to excellent yield, whereas
methanol, THF, toluene, dioxane, and dichloromethane gave
slower reactions with moderate yields. The results are summa-
rized in Table 1.
One of the most important reactions, which finds applica-
tions in the synthesis of many substances such as drugs,
materials, and natural products,1 is the formation of new carbon-
nitrogen bonds from simple and easily available starting
materials.2 Over the last few decades, a very efficient reaction,
which involves the use of azodicarboxylates as electrophiles for
the formation of carbon-nitrogen bonds, has been successfully
used.3 The efficiency of the reaction is reported to be the result
of the strong electron-withdrawing nature of azodicarboxylate
acceptors possessing a vacant orbital.4 Over the years, various
reactions such as zwitterion intermediate reactions,5,6 electro-
philic ¡-amination of carbonyl compounds,7,8 C-H activation at
the ¡-positions of amines and ethers,9,10 and ene-type reactions
with olefins11-13 in the presence of azodicarboxylates have
been extensively studied. In addition, various other methods
for hydroacylation reactions with aldehydes using a range of
reagents and catalysts, for example, ionic liquids such as 1-n-
butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide
([BMIM][NTf2])14 including water15 without a catalyst, and
transition-metal catalysts,16 have been reported. All the above
methods suffer from drawbacks and limitations such as choice of
substrate, atom economy, reusability of the catalyst, and the
reaction efficiency. Nanocatalysts having high surface area to
volume ratios are expected to display unique electronic proper-
ties that may influence the reaction. To our knowledge, the
reactions of aldehydes with azodicarboxylates have not yet been
explored using nano copper oxide as a catalyst. Herein, we
report a green cross-coupling reaction of a range of aldehydes
with an azodicarboxylate, using a novel catalyst, namely CuO
We screened various catalysts for the hydroacylation
reaction in acetonitrile solvent at 60 °C; the results are summa-
rized in Table 2. It is clear from the table that only CuO-np/SiO2
provides good yields of the product compared to RuCl3, RhCl3,
Cu(OAc)2, CuO, and CuO-np without the support provided a
poor yield with the problem of catalyst recovery. We also studied
the effect of different CuO-np loadings on the silica support for
Table 1. Effect of solvent on hydroacylation reaction catalyzed
a
by CuO-np/SiO2
O
O
O
N
CuO-np/SiO2
O
N
O
CHO
N
O
O
N
O
Solvent, 60 °C
H
O
Entry
Solvent
Yieldb/%
1
2
3
4
5
CH3CN
THF
Toluene
Dioxane
88, 57c
62
56
69
R
O
O
O
O
CuO-np/SiO2
Methanol
73
O
N
R
CHO
O
N
N
O
+
N
H
O
aReaction conditions: diisopropyl azodicaboxylate (1 mmol),
CuO-np/SiO2 (10 mol %), benzaldehyde (1.2 mmol), solvent
CH3CN, 60 °C
O
b
c
(5 mL), 60 °C, 24 h. Isolated yields. Reaction carried out at
Scheme 1. CuO-np/SiO2-catalyzed hydroacylation reaction of
aldehydes and azodicaboxylate.
room temperature, 24 h.
Chem. Lett. 2012, 41, 1484-1486
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1485
Table 2. Effect of catalyst loading on hydroacylation reactiona
Table 3. CuO-np/SiO2-Catalyzed hydroacylation reaction of
aldehyde and isopropyl azodicaboxylatea
O
O
O
N
CuO-np/SiO2
O
R
O
N
O
O
CHO
O
CuO-np/SiO2
N
O
O
O
N
N
O
R
CHO
O
N
N
O
CH3CN, 60 °C
H
+
N
H
O
O
CH3CN, 60 °C
O
O
Loading
/mol %
Entry
Catalyst
Yieldb/%
Time
/h
Yieldb
/%
Entry
1
Aldehyde
CHO
Product
1
2
3
4
5
6
7
8
9
RuCl3
RhCl3
Cu(OAc)2
CuO
10
10
10
10
10
®
2
47
39
58
26
57
O
O
24
85
N
O
83c
N
O
H
O
H3CO
CuO-np
O
O
CHO
CHO
H3CO
2
24
90
O
N
N
H
O
Without catalyst
CuO-np/SiO2
CuO-np/SiO2
CuO-np/SiO2
No reaction
O
48
62
88
OCH3
H3CO
H3CO
5
10
H3CO
H3CO
H3CO
O
O
O
N
3
4
26
18
26
28
24
24
36
24
12
15
18
30
92
87
89
88
79
82
78
60
95
93
90
63
N
H
O
O
O
aReaction conditions: diisopropyl azodicaboxylate (1 mmol),
benzaldehyde (1.2 mmol), CuO-np/SiO2 (10 mol %), CH3CN
(5 mL), 60 °C, 24 h. Isolated yields.
H3C
O
O
b
O
N
N
H3C
HO
CHO
H
O
the hydroacylation reaction, and the data are presented in
Table 2. The table shows that a 10 mol % copper(II) oxide
nanoparticle loading on silica gives excellent results compared
to 2 and 5 mol % copper loadings on silica, indicating the role of
catalyst size in the reaction. However, needless to say, no
product formation occurs in the absence of the catalyst under the
same reaction conditions.
HO
O
O
O
O
O
N
N
CHO
CHO
N
H
O
O
5
O
O
O
HO
Cl
N
H
6
HO
Cl
Electronic factors also play an important role in the reaction.
In order to understand the electronic factors, the study was
extended to aldehydes with different substituents. Table 3
presents the relevant data. Benzaldehydes with electron-donating
groups, such as 4-methoxybenzaldehyde, 3,4,5-trimethoxy-
benzaldehyde, 4-methylbenzaldehyde, 4-hydroxybenzaldehyde,
and 3-hydroxybenzaldehyde, provided excellent yields in short
reaction times (Table 3, Entries 2-6) compared to benzaldehyde
with electron-withdrawing groups, such as 4-bromobenzalde-
hyde, 4-chlorobenzaldehyde, 2,6-dichlorobenzaldehyde, and 4-
nitrobenzaldehyde, which needed longer reaction times and gave
moderate yields (Table 3, Entries 7-10). Thiophen-2-carbalde-
hyde provided an excellent yield (Table 3, Entry 11). Aliphatic
aldehydes (Table 3, Entries 12 and 13) underwent smooth
reactions with excellent yields, compared to benzaldehyde
(Table 3, Entry 1). A dialdehyde provided a poor yield (Table 3,
Entry 14), compared to the other aldehydes. It is clear from the
table that aliphatic aldehydes give better yields than aromatic
aldehydes, indicating the influence of the electronic properties of
the substrates. It is also apparent from the table that electron-
withdrawing groups decrease the overall yields of the reactions.
These results make the process more attractive and interesting
with respect to the economy and simplicity of the process.
The reusability of the silica-supported CuO nanoparticles
catalyst was studied for the hydroacylation reaction of benzal-
dehyde with diisopropyl azodicarboxylate in acetonitrile solvent
at 60 °C. CuO-np/SiO2 was recovered quantitatively by simple
filtration, and reused; it gave consistent activity even after the
fifth cycle (Table 3, Entry 1). The absence of copper in the
filtrate, measured by atomic absorption spectroscopy, confirmed
that no leaching of copper occurred during the reaction. These
results make the process more attractive and interesting with
respect to the economy and simplicity of the process.
O
O
O
N
N
O
O
7
CHO
CHO
N
H
O
O
O
O
Br
O
8
Br
N
H
Cl
Cl
Cl
O
O
Cl
CHO
O
N
9
N
H
O
O
O
O2N
O
O
N
10
11
12
13
14
O2N
CHO
N
H
O
O
N
O
S
O
O
O
O
CHO
S
N
H
O
O
O
O
O
O
N
N
CHO
CHO
N
H
O
O
O
N
H
O
O
O
O
O
N
N
O
H
O
O
OHC
CHO
N
O
N
O
H
O
aReaction conditions: diisopropyl azodicaboxylate (1 mmol),
benzaldehyde (1.2 mmol), CuO-np/SiO2 (10 mol %), CH3CN
(5 mL), 60 °C. bIsolated yields. cIsolated yield after fifth cycle.
Chem. Lett. 2012, 41, 1484-1486
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

1486
In conclusion, a green, inexpensive, and efficient method for
3614. b) R. Grigg, J. Kemp, J. Chem. Soc., Chem. Commun.
1977, 125.
12 a) H.-S. Dang, A. G. Davies, J. Chem. Soc., Perkin Trans. 2
1991, 721. b) Y. Leblanc, R. Zamboni, M. A. Bernstein,
J. Org. Chem. 1991, 56, 1971.
13 a) T. K. Sarkar, B. K. Ghorai, S. K. Das, P. Gangopadhyay,
P. S. V. S. Rao, Tetrahedron Lett. 1996, 37, 6607. b) A. A.
Aly, S. Ehrhardt, H. Hopf, I. Dix, P. G. Jones, Eur. J. Org.
Chem. 2006, 335.
14 B. Ni, Q. Zhang, S. Garre, A. D. Headley, Adv. Synth. Catal.
2009, 351, 875.
the hydroacylation of various aldehydes with diisopropyl
azodicarboxylate, using a silica-supported nanocopper catalyst,
in good to excellent yields is provided. The effects of solvent,
catalyst loading, and substituents on the aldehyde are studied.
The choice of aldehyde is paramount in the selectivity of the
reaction. The protocol used is inexpensive and the CuO-np/SiO2
catalyst is recyclable; no additional ligands and additives are
required, so the method is simple, economical, and has practical
advantages for the synthesis of biologically active heterocyclic
compounds.
15 Q. Zhang, E. Parker, A. D. Headley, B. Ni, Synlett 2010,
2453.
Financial assistance from the Indira Gandhi Centre for
Atomic Research (IGCAR), Kalpakkam, India is kindly ac-
knowledged.
16 a) D. Lee, R. D. Otte, J. Org. Chem. 2004, 69, 3569. b) Y. J.
Kim, D. Lee, Org. Lett. 2004, 6, 4351. c) Y. Qin, Q. Peng, J.
Song, D. Zhou, Tetrahedron Lett. 2011, 52, 5880.
17 General experimental procedure for the CuO-np/SiO2-
catalyzed hydroacylation reaction of aldehydes with
azodicarboxylate:
References and Notes
1
a) R. A. Sheldon, Green Chem. 2008, 10, 359. b) P. T.
Anastas, M. M. Kirchhoff, Acc. Chem. Res. 2002, 35, 686.
For selected reviews, see: a) R. Matsubara, S. Kobayashi,
Acc. Chem. Res. 2008, 41, 292. b) M. Beller, J. Seayad, A.
Tillack, H. Jiao, Angew. Chem., Int. Ed. 2004, 43, 3368.
a) V. Nair, R. S. Menon, A. R. Sreekanth, N. Abhilash, A. T.
Biju, Acc. Chem. Res. 2006, 39, 520. b) J. F. Hartwig,
Science 2002, 297, 1653. c) M. Beller, T. H. Riermeier, in
Transition Metals for Organic Synthesis: Building Blocks
and Fine Chemicals, ed. by M. Beller, C. Bolm, Wiley-
VCH, 1998, Vol. 1, p. 184.
2
Diisopropyl azodicarboxylate (1 mmol), aldehyde (1.2
mmol), and CuO-np/SiO2 (10 mol %) were stirred in ace-
tonitrile solvent (5 mL) at 60 °C. The progress of the reaction
was monitored by TLC. After the appropriate time in Table 3
reaction mixture was diluted with 20 mL of acetonitrile
and catalyst was separated by filtration, the solvent was
evaporated and the residue purified by column chromatog-
raphy on silica gel using hexane-ethyl acetate (80:20) as
eluent to afford the pure product. All products were
3
4
1
a) B. Shen, D. M. Makley, J. N. Johnston, Nature 2010, 465,
1027. b) P. Thansandote, E. Chong, K.-O. Feldmann, M.
Lautens, J. Org. Chem. 2010, 75, 3495. c) H. Shen, Z. Xie,
J. Am. Chem. Soc. 2010, 132, 11473.
characterized by H NMR and 13C NMR.
Spectral data for selected compounds
Spectral data for Hydroacylation product (Table 3,
Entry 1), Yield: 85%; 1H NMR (200 MHz, CDCl3): ¤
1.04-1.07 (d, 6H), 1.26 (d, 6H), 4.83 (m, 2H), 7.10 (s, 1H),
7.38-8.10 (m, 5H); 13C NMR (200 MHz, CDCl3): ¤ 21.31,
21.91, 70.41, 72.15, 127.96, 130.13, 131.72, 133.37, 135.21,
152.8, 155.21, 170.7. Anal. Calcd for C15H20N2O5: C, 58.43;
H, 6.54; N, 9.09%. Found: C, 58.21; H, 6.62; N, 9.13%.
Hydroacylation product (Table 3, Entry 2), Yield: 90%;
1H NMR (200 MHz, CDCl3): ¤ 1.11 (d, 6H), 1.29 (d, 6H),
3.84 (s, 3H), 4.86 (m, 2H), 5.28 (s, 1H), 6.85 (dd, 2H), 7.68-
8.05 (dd, 2H); 13C NMR (200 MHz, CDCl3): ¤ 21.58, 22.03,
56.32, 70.41, 72.03, 113.37, 121.1, 131.12, 132.34, 153.2,
155.31, 162.97. Anal. Calcd for C16H22N2O6: C, 56.80; H,
6.55; N, 8.28%. Found: C, 56.68; H, 6.61; N, 8.32%.
18 S. K. Mandal, S. M. Inamdar, V. K. More, A. Niphade, WO
Patent 2010086876, 2010.
5
6
a) E. Brunn, R. Huisgen, Angew. Chem., Int. Ed. Engl. 1969,
8, 513. b) R. D. Otte, T. Sakata, I. A. Guzei, D. Lee, Org.
Lett. 2005, 7, 495.
a) V. Nair, A. T. Biju, A. U. Vinod, E. Suresh, Org. Lett.
2005, 7, 5139. b) V. Nair, A. T. Biju, K. Mohanan, E. Suresh,
Org. Lett. 2006, 8, 2213.
7
8
R. Zhu, D. Zhang, J. Wu, C. Liu, Tetrahedron: Asymmetry
2007, 18, 1655.
a) C. Thomassigny, D. Prim, C. Greck, Tetrahedron Lett.
2006, 47, 1117. b) X. Liu, H. Li, L. Deng, Org. Lett. 2005, 7,
167.
9
a) O. Diels, E. Fischer, Ber. Dtsch. Chem. Ges. 1914, 47,
2043. b) R. Huisgen, W. Rapp, I. Ugi, H. Walz, I. Glogger,
Justus Liebigs Ann. Chem. 1954, 586, 52.
10 a) G. Doleschall, Tetrahedron Lett. 1978, 19, 2131. b)
B. Abarca, R. Ballesteros, E. González, P. Sancho, J.
Sepúlveda, C. Soriano, Heterocycles 1990, 31, 1811.
19 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
11 a) L. M. Stephenson, D. L. Mattern, J. Org. Chem. 1976, 41,
Chem. Lett. 2012, 41, 1484-1486
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/