Cu-Mn bimetallic catalyst for Huisgen [3+2]-cycloaddition

Article abstract of DOI:10.1039/c005088a

Cu-Mn spinel oxide catalyst has been investigated for the ligand-free Huisgen [3+2] cycloaddition. The copper(i) species required in the cycloaddition reaction has been stabilized in the tetrahedral site of the spinel without the need of a stabilizing age

Full text of DOI:10.1039/c005088a

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Cu–Mn bimetallic catalyst for Huisgen [3+2]-cycloaddition†
Syed Khalid Yousuf,a Debaraj Mukherjee,*a Baldev Singh,b Sudip Maityc and Subhash Chandra Tanejaa
Received 14th April 2010, Accepted 15th July 2010
DOI: 10.1039/c005088a
Table 1 Comparative study of the effect of three different catalysts and
various solvents on the reaction of a and b to yield the product c
Cu–Mn spinel oxide catalyst has been investigated for
the ligand-free Huisgen [3+2] cycloaddition. The copper(I)
species required in the cycloaddition reaction has been
stabilized in the tetrahedral site of the spinel without the
need of a stabilizing agent. The new catalyst is robust and
can be reused several times under MW conditions with
negligible loss in catalytic activity.
S.No.
Catalysta
Solventb
Time/h
Yield (%)c
1
2
3
4
5
6
7
8
A
B
C
D
A
A
A
A
B
C
D
CH3CN
CH3CN
CH3CN
CH3CN
DMF
THF
Toluene
Solvent free (Mw)
Solvent free (Mw)
Solvent free (Mw)
Solvent free (Mw)
8
8
8
15
12
12
12
0.05
0.05
0.05
0.05
99
94
73
52d
77
78
78
99
98
75
58d
Bimetallic catalysts in which one metal can finetune or modify
the catalytic properties of the other metal offer consider-
able promise in the area of fundamental organic transfor-
mations such as C–C bond formation,1 hydrogenation,2 and
cycloaddition.3 In a bimetallic catalyst, metal type, oxidation
state and concentration can be varied to modulate the catalytic
performance.4 For example, addition of a second metal to a
noble metal catalyst alters catalytic performance to an extent
not accountable by a simple superposition of monometallic
properties.5 The formation of a bimetallic phase changes the
geometry of the available sites either by generation of entirely
new spinel structures or by limiting the ensemble of each
component metal.6 Thus, alteration of either the electronic
or geometric properties of an active site may change the
adsorption energetics of the reactants and the products resulting
in higher activity7 or suppression of side reactions, culminating
in improved selectivity. Despite having these qualities, the scope
of bimetallic catalysts in organic synthesis has not been studied
in detail. Herein, we report the use of a bimetallic catalyst in
the Huisgen [3+2] cycloaddition reaction also known as click
chemistry.8
Copper(I) salts are quite prone to redox processes and it
is desirable to protect and stabilize the active copper cata-
lysts during the azide–alkyne cycloaddition reaction (CuAAC).
Nanopowders,9 copper nanoclusters,10 solid supported Cu on
titanium oxide or zeolites,11 porphyrinatocopper nanoparticles12
as well as Cu(I) salts13 in the presence of phosphorous or nitrogen
bases14 (ligands) have been used for this purpose. However, all the
above mentioned methods suffer from low product yields, low
activities, require additives,15 high reaction temperature15 and
are generally accompanied by the formation of side products
like bistriazole, diacetylenes etc.12
9
10
11
a Catalytic loading used is 10 mg g-1 of a. b 5 ml g-1 of the reactant.
c Isolated but not optimised yield. d Mixture of products obtained.
Copper-manganese spinels have attracted significant atten-
tion for their potential applications in electrochemical systems.16
Recently Cu–Mn spinel oxide catalysts were used17 in the
combined steam reforming of methanol. Tang18 and his team
studied the load of Cu–Mn/zeolite–Y for the synthesis of
dimethyl ether from CO–H2. Despite their low surface areas,
these catalysts displayed activity comparable to a commercial
Cu–Zn–Al catalyst. We conceptualized that the incorporation
of low concentrations of p-type semiconductors like CuO in the
matrix of an n-type manganese oxide may result in an increase in
acceptor centres, allowing absorption of a considerable amount
of substrates. Consequently in a Cu–Mn bimetallic catalyst the
reaction between CuO and Mn2O3 through electron transfer
from Mn3+ to Cu2+ may result in the formation of an Mn4+
ion having a bias for d2sp3 bonds preferring the octahedral
site, and a Cu+ ion by virtue of its preference to form sp3
bonds will be stabilized at the tetrahedral site thus obviating
the need for an external reagent. In order to substantiate the
above concept, we prepared four different bimetallic catalysts
by varying the Cu : Mn ratio. The catalytic activities of all four
copper containing catalysts were examined in a model reaction
between benzylazide and methylpropiolate in a 1 : 1 molar ratio
(Scheme 1) in different solvent systems at room temperature as
well as under solvent free conditions using microwaves (MW)
(Table 1). The specific surface area of the catalysts was also
determined in order to examine its effect on catalytic activity
(Table 2).
aBio-Organic Chemistry Division, Indian Institute of Integrative
Medicine (CSIR), Canal Road, Jammu, India 180001.
E-mail: mukherjee@
iiim.res.in
bCatalyst Discipline, Indian Institute of Integrative Medicine (CSIR),
Canal Road Jammu, India 180001
cCMFIR, Dhanbad, Jharkhand, India
† Electronic supplementary information (ESI) available: General infor-
mation, experimental procedures and 1H NMR and 13C NMR spectra
of some selected compounds. See DOI: 10.1039/c005088a
Scheme 1
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Table 2 Relation between catalytic activity and specific surface areaa
of the catalyst
Composition
Calcination
Specific surface area
of the catalyst/m2 g-1
Catalyst Cu : Mn (mol ratio) temp./◦C
E
D
C
B
A
Only CuCl
Only CuCl2
3 : 0.25
1 : 0.25
2 : 0.25
2 : 0.25
2 : 0.25
450
450
450
450
450
350
300
21.0
4.62
8.30
16.4
18.30
11.31
9.21
a Determined from Chembet-3000TPR/TPD.
Table 3 Comparisons of reaction conditions and yields in the synthesis
of c by catalyst A
S.No.
Methoda
Time
Yield (%)
1
2
3
4
5
a
b
c
d
e
8 h.
5 h.
3 h.
30 min.
3 min.
99
90
Mixture of products
95
99
a a. Reaction with CH3CN at room temperature. b. Reaction with
CH3CN under reflux c. Solvent free conventional heating. d. MW-
acetonitrile. e. MW-solvent free. In all cases catalyst-A was used.
Fig. 1 Powder X-ray diffraction (XRD) of the samples.
Cat-C, having a very small amount of M-C phases [lin (count)
600], showed moderate activity, Cat-D, which is completely
devoid of M-C phases, showed poor catalytic activity. On the
other hand, enhanced activity was observed with Cat-B having
distinct M-C phases. Optimum activity was observed with Cat-A
having maximum M-C phases [lin (count) 800]. Greater activity
of spinel oxide may be due to the formation of phases with less
ordered arrangements.
However, a small increase in the amount of Cu or Mn results
in lower activity, which may be due to blocking of the active sites
of the spinel.
The new bimetallic catalyst was easily recovered by filtration
after each experiment and could be reused for 1,2,3-triazole syn-
thesis in more than nine successive reactions without significant
loss of the catalytic activity (Fig. 2).
The results revealed that catalyst A was the most effective
among all other catalysts, thus yielding the corresponding 1,4-
substituted 1,2,3-triazole as a sole reaction product. During
the standardisation of the reaction conditions with catalyst A
(Table 3), it was observed that the reaction without solvent under
MW was the most favourable condition for complete conversion.
In order to explore the versatility and functional group
tolerance of the bimetallic catalyst A, we performed a series
of click reactions to produce 1,4-disubstituted 1,2,3-triazoles in
good to excellent yields under both solution and MW condi-
tions (Table 4). Carbohydrate based alkynes reacted smoothly
without affecting acetonide and acetate protection, affording the
corresponding triazoles (entries 12, 13, 14) in good to excellent
yields. After getting positive results from initial experiments we
turned our attention to the b-hydroxy-1,2,3-triazole unit due to
its importance as a replacement for peptide groups in HIV-1
protease inhibitors.19 The new catalyst system also facilitated
the formation of furan derived b-hydroxy triazole derivatives
(entries 6, 11, 12, 13, 14). Triazole glycoconjugates have also
been synthesised possessing a b-hydroxy furan group. The most
striking feature of the reaction was the synthesis of a silylated
triazole by the reaction of TMS-acetylene with the iodoazide
derivative of DHF (entry 15), whereas the formation of TMS
triazoles has reportedly been a failure under other catalytic
systems.11
In order to understand the efficiency of catalytic activity as
a function of overall composition, it is imperative to locate the
kind of phase/s making the largest contribution to the metal
surface area and thus performing the main burden of catalytic
action. Thus, the powder X-ray diffraction (XRD) of the samples
were recorded (Fig. 1) and results for the four catalysts are
summarized in Table 5. The data reveal that copper manganese
oxide (M-C) phases are essential for the catalytic activity. While
Fig. 2 Recyclability of Cat-A for 1,2,3-triazole synthesis.
It can be clearly seen from the SEM images (Fig. 3) that the
morphology and the structural integrity of the Cu–Mn spinel
remain almost uniform at the end of run 10, also supported by
the XRD spectra of the used catalyst (Supporting information†).
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Table 4 Azide–alkyne cycloaddition by bimetallic catalyst-A
Time for solution phase a
(hr)/MW conditions/min
Yield for solution
Entry
1
R
R¢
phase/Mw conditions%a
4/3
4/3
95/99
2
3
96/99
95/99
4/3
4/3
4
95/99
5
6
4/3
4/3
95/99
96/99
7
8
4/3
5/3
95/99
96/99
9
5/3
5/3
94/99
95/98
10
11
5/3
96/99
12
13
5/5
5/5
95/99
95/99
14
15
5.5/3
5/5
96/99
90/97
a All refer to isolated yield
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Table 5 Results of XRD for the catalyst
General experimental procedure for microwave assisted reactions
Sample no
CAT-A
Phases presenta
Equimolecular amounts of azide (1.0 mmol) and alkyne
(1.ommol) were dissolved in 0.5 mL of CH3CN and the solution
was adsorbed on a bimetallic catalyst (10 mg g-1 of reactant) in a
beaker, placed into the microwave cavity. Microwave irradiation
of 100 W was used, the temperature being ramped from room
temperature to 120 ◦C. Once 120 ◦C was reached, the reaction
mixture was held at this temperature for 3 min. After completion
of the reaction by TLC, ethyl acetate–acetone (5 : 1 v/v, 10 mL)
was added to the reaction mixture, stirred for 15 min, centrifuged
and filtered. The bimetallic catalyst was washed twice with ethyl
acetate–acetone (5 mL ¥ 2) and dried for further use. The
organic phase was dried over anhydrous Na2SO4. The solvent
was removed by evaporation under reduced pressure to afford
the corresponding triazole. The product was recrystallized from
95% ethanol or purified by column chromatography on silica gel
using petroleum ether–ethyl acetate as the eluent to obtain the
pure product.
Tenorite (CuO); Copper Manganese Oxide
(Cu1.4Mn1.6O4); Hausmannite, (Mn3O4);
Manganese Chloride Hydrate,
(MnCl2·2H2O); Crednerite (CuMn2O4)
Tenorite (CuO); Copper Manganese Oxide
(Cu1.4Mn1.6O4); Hausmannite, (Mn3O4);
Manganese Chloride Hydrate,
(MnCl2·2H2O); Crednerite (CuMn2O4)
Tenorite (CuO); Copper Manganese Oxide
(Cu1.4Mn1.6O4)
CAT-B
CAT-C
CAT-D
Tenorite (CuO)
a The phases are identified by a search match procedure with the help of
DIFFRACPLUS software using JCPDS databank.
Acknowledgements
Authors thank Dr P. R. Sharma, Technical officer for providing
SEM images of the catalysts. The financial support provided by
CSIR is gratefully acknowledged.
Fig. 3 SEM images of catalyst-A before use (X) and after run 10 (Y).
References
1 C. Lo¨fberg, R. Grigg, A. Keep, A. Derrick, V. Sridharan and C.
Kilner, Chem. Commun., 2006, 5000.
2 B. M. Reddy, G. K. Reddy, K. N. Rao, A. Khan and I. Ganesh,
J. Mol. Catal. A: Chem., 2007, 265, 276.
3 S. Kamijo and Y. Yamamoto, J. Org. Chem., 2003, 68, 4764.
4 C. Lo¨fberg, R. Grigg, A. Keep, A. Derrick, V. Sridharana and C.
Kilner, Chem. Commun., 2006, 5000.
5 P. Bodnariuk, B. Coq, G. Ferrat and F. Figueras, J. Catal., 1989,
116, 459; J. H. Sinfelt, Adv. Catal., 1973, 23, 91; J. S. Campbell
and C. Kemball, Trans. Faraday Soc., 1961, 57, 809; J. J. Burton,
R. L. Garten, in: Adv. Mater. Catal. (J. J. Burton and R. L. Garten,
ed.) Academic Press, New York, 1977, 33; Yu. I. Yermakov, B. N.
Kuznetsov and V. A. Zakharov, “Catalysis by Supported Complexes”,
Elsevier, Amsterdam, 1981.
6 W. M. H. Sachtler and R. A. van Santen, Adv. Catal., 1977, 26, 69.
7 C. H. F. Peden and D. W. Goodman, J. Catal., 1987, 104, 347; F. M.
Dautzenberg, J. N. Helle, P. Biloen and W. M. H. Sachtler, J. Catal.,
1980, 63, 119; J. L. Carter, G. B. McVicker, J. Weissman, W. S. Kmak
and J. H. Sinfelt, Appl. Catal., 1982, 3, 327.
8 H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew. Chem., 2001,
113, 2056; H. C. Kolb, M. G. Finn and K. B. Sharpless, Angew.
Chem., Int. Ed., 2001, 40, 2004.
Finally, the amount of Cu–Mn contamination in the product
(crude triazole) after filtration was tested by atomic absorption
spectrometer (Supporting information†). It was observed that
the amount of Cu-contamination was below detection level in
the products, while the levels of Mn were registered in the range
of ~110 ppb after 10 cycles.
In summary we have demonstrated the applicability of the first
example of a Cu–Mn bimetallic catalyst for an azide–alkyne
cycloaddition reaction (CuAAC). The catalyst is robust and
can be reused with negligible loss in catalytic activity, both in
solution phase and under MW conditions, without the need of
a stabilizing agent. Recyclability of the catalyst, the solvent free
MW conditions and the atom economy make the process green.
It is remarkable that despite its low intrinsic catalytic activity,
Mn can significantly influence the activity and selectivity of a
Cu–Mn spinel oxide.
9 A. A. Mirzaei, H. R. Shaterian, M. Habibi, G. J. Hutchings and
S. H. Taylor, Appl. Catal., A, 2003, 253, 499; H. Yahiro, K. Nakaya,
T. Yamamoto, K. Saiki and H. Yamaura, Catal. Commun., 2006, 7,
228; D. C. Yeragi, N. C. Pradhan and A. K. Dalai, Catal. Lett., 2006,
112, 139; M. R. Morales, B. P. Barbero and L. E. Cadu´s, Appl. Catal.,
B, 2006, 67, 229.
10 L. D. Pachon, J. H. van maarseveen and G. Rothenberg, Adv. Synth.
Catal., 2005, 347, 811.
11 S. Chassaing, A. S. S. Sido, A. Alix, M. Kumarraja, P. Pale and J.
Sommer, Chem.–Eur. J., 2008, 14, 6713; K. Yamaguchi, T. Oishi, T.
Katayama and N. Mizuno, Chem.–Eur. J., 2009, 15, 10464.
12 H. Sharghi, M. H. Beyzavi, A. Safavi, M. M. Doroodmand and R.
Khalifeh, Adv. Synth. Catal., 2009, 351, 2391.
Experimental section
Catalyst preparation
Aqueous solutions of CuCl2·2H2O and MnCl2·4H2O in a molec-
ular weight ratio of 2 : 0.25 were co-added at a rate of 1 mL min-1
under vigorous mechanical stirring at room temperature to form
a uniform solution. To the solution, ammonium solution was
added drop by drop until pH 8.5 to 8.7 and allowed to stand
overnight to form a gel, filtered and washed with double distilled
water till free from chloride ions. After keeping overnight at
room temperature the cake was allowed to dry in an air oven at
13 Z. X. Wang and H. L. lin, Chem. Commun., 2003, 2450; V. Aucagne
and D. A. Leigh, Org. Lett., 2006, 8, 4505.
14 F. Pe´rez-Balderas, M. Ortega-Mun˜oz, J. Morales-Sanfrutos, F.
Herna´ndez-Mateo, F. G. Calvo-Flores, J. A. Calvo-As´ın, J. Isac-
Garc´ıa and F. Santoyo-Gonza´lez, Org. Lett., 2003, 5, 1951; T. R.
◦
◦
110 C for 24 h and finally calcined (10 C min-1) in a muffle
furnace at 425 ◦C for three hours.
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Chan, R. Hilgraf, K. B. Sharpless and V. V. Fokin, Org. Lett., 2004, 6,
2853; B. Gerard, J. Ryan, A. B. Beeler and J. A. J. Porco, Tetrahedron,
2006, 62, 6405; J. Broggi, S. D´ıez-Gonza´lez, J. L. Petersen, S. Berteina-
Raboin, S. P. Nolan and L. A. Agrofoglio, Synthesis, 2008, 141; A.
Marra, A. Vecchi, C. Chiappe, B. Melai and A. Dondoni, J. Org.
Chem., 2008, 73, 2458; V. O. Rodionov, S. I. Presolski, D. D. Diaz,
V. V. Fokin and M. G. Finn, J. Am. Chem. Soc., 2007, 129, 12705.
15 S. Chassing, M. Kumarraja, A. S. S. Sido, P. Pale and J. Sommer,
Org. Lett., 2007, 9, 883.
16 B. E. Martin and A. Petric, J. Phys. Chem. Solids, 2007, 68,
2262.
17 H. A. Orgueira, D. Fokas, Y. Isome, P. C. M. Chan and C. M. Baldino,
Tetrahedron Lett., 2005, 46, 2911.
18 X-J Tang, J-H Fei, Z-Y Hou, X-M Zheng and Hui Lou, Energy
Fuels, 2008, 22, 2877.
19 A. Brik, J. Alexandratos, Y. Lin, J. H. Elder, A. J. Olson, A.
Wlodawer, D. S. Goodsell and C. Wong, ChemBioChem, 2005, 6,
1167.
1572 | Green Chem., 2010, 12, 1568–1572
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The Royal Society of Chemistry 2010
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