Copper-catalyzed highly efficient aerobic oxidative synthesis of imines from alcohols and amines

Article abstract of DOI:10.1039/c2gc16548a

A highly efficient and green tandem imine synthesis from alcohol and amine with molecular oxygen as oxidant was achieved by using a remarkable low catalyst-loading, with a commercially available and environmentally benign copper catalyst.

Full text of DOI:10.1039/c2gc16548a

View Online / Journal Homepage / Table of Contents for this issue
Dynamic Article Links
Green Chemistry
Cite this: Green Chem., 2012, 14, 1016
www.rsc.org/greenchem
PAPER
Copper-catalyzed highly efficient aerobic oxidative synthesis of imines from
alcohols and amines
Qiang Kang and Yugen Zhang*
Received 2nd December 2011, Accepted 10th January 2012
DOI: 10.1039/c2gc16548a
A highly efficient and green tandem imine synthesis from alcohol and amine with molecular oxygen as
oxidant was achieved by using a remarkable low catalyst-loading, with a commercially available and
environmentally benign copper catalyst.
Fe2O3 (entry 1, Table 1) and 46% yield with CuCl2 (entry 2),
respectively. The copper catalyst exhibits better activity than the
Introduction
Imines are an important class of nitrogen-containing compounds
which are used for organic synthesis, pharmaceuticals and agri-
cultural chemicals.1–4 They are often employed either as electro-
philic reactants in different types of transformations such as
asymmetric2 and multi-component synthesis3 or as directing
groups in C–H bond activation reactions.4 Therefore, the
efficient and diverse synthesis of imines is a consistently
demanding research topic in the organic synthetic community.
Traditionally, imines are synthesized from aldehydes or
ketones with amines by a condensation reaction.5 Several new
approaches have also been developed in recent years either by
using a homogeneous catalyst6 or a heterogeneous catalyst.7
Among these transformations, oxidative coupling of alcohols
and amines represent the most straightforward way to produce
imines. Since the ground-breaking work of Milstein and co-
workers, second-row and third-row transition metals such as
ruthenium,6a osmium6b and palladium6c have already been
chosen as catalysts. On the other hand, platinum and gold have
also been applied as heterogeneous catalysts. Considering the
limited supply of precious and rare metals,8 it is urgent for che-
mists to explore the potential catalysis by common metals such
as copper9,10 and iron.11 In this work, we demonstrate that
copper is a highly efficient homogeneous catalyst in the oxi-
dative coupling reaction of alcohols with primary amines to form
the corresponding imines. Molecular oxygen was employed as
the green oxidant in this transformation.
iron one. Therefore, various copper catalysts including copper(I)
and copper(II) were examined in this oxidative coupling reaction
with KOH as base instead of Cs2CO3. In general, copper(II) cata-
lysts showed better selectivity than copper(I) catalysts. For
example, the reactions with CuBr and CuCl as catalyst only
afforded 35% (entry 3) and 50% yield (entry 4) of the desired
imine with full conversion of the starting material. On the con-
trary, reactions employing copper(II) catalyst such as CuCl2, Cu
(OAc)2, Cu(ClO4)2·6H2O, Cu(OTf)2 and Cu(NO3)2·5H2O pro-
duced the corresponding imine with good to excellent yields
(entries 5–9, Table 1). Cu(ClO4)2·6H2O exhibited the highest
activity (90% yield, entry 7) among the catalysts which were
tested. Cu2O was also investigated as a heterogeneous catalyst in
this reaction which gave the desired imine in 87% yield (entry
10). The control reaction without benzyl alcohol gave a trace
Table 1 Catalyst screeninga
Entry
Catalyst
Base
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
Fe2O3
CuCl2
CuBr
CuCl
Cs2CO3
Cs2CO3
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
17
17
19
19
19
19
19
19
19
19
19
25
46
35
50
72
80
90
89
87
87
<5
Results and discussion
CuCl2
Cu(OAc)2
Cu(ClO4)2·6H2O
Cu(OTf)2
Cu(NO3)2·5H2O
Cu2O
Initially, the coupling reaction of benzyl alcohol (1a) and benzyl
amine (2a) was investigated in the presence of a commercially
available iron or copper catalyst and 1.5 equivalent of Cs2CO3 in
toluene at 70 °C under oxygen atmosphere. The reaction went
smoothly to afford the corresponding imine in 25% yield with
9
10
11c
Cu(ClO4)2·6H2O
a Reaction conditions: 5 mol% of catalyst, 1.0 mmol of 1a, 1.5 mmol of
2a, 1 mL toluene, 23 °C. b Determined by 1H NMR with N,N-
dicyclohexylmethylamine as an internal standard. c Reaction with 2a
only (no 1a was added).
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way,
The Nanos, Singapore 138669, Singapore. E-mail: ygzhang@
ibn.a-star.edu.sg; Fax: (+65)-6478-9020
1016 | Green Chem., 2012, 14, 1016–1019
This journal is © The Royal Society of Chemistry 2012

View Online
Table 2 Optimization of base, solvent and temperaturea
Table 3 Investigation of substrate scopea
Entry
Base, x (mol%)
Solvent
Temp (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
KOH, 0
KOH, 5
KOH, 10
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
MeCN
DCM
THF
MeOH
H2O
Toluene
Toluene
70
70
70
70
70
70
70
70
70
70
40
40
70
70
23
23
48
49
47
84
90
7
27
38
39
5
27
37
58
Trace
49
54
Time
(h)
Yield of
Entry
1
2
3b (%)
KOH, 100
KOH, 150
K2CO3, 150
NaOH, 150
KOtBu, 150
DB, 150
KOH, 150
KOH, 150
KOH, 150
KOH, 150
KOH, 150
KOH, 150
KOH, 150
1
2
3
4
5
6
7
8
9
PhCH2OH (1a) PhCH2NH2 (2a)
PhCH2OH (1a) n-Butyl-NH2 (2b)
PhCH2OH (1a) Dodecyl-NH2 (2c)
19
19
19
90
83
80
63
Trace
Trace
97
94
90
PhCH2OH (1a) Cyclohexyl-NH2 (2d) 19
PhCH2OH (1a) Allyl-NH2 (2e)
PhCH2OH (1a) Propargyl-NH2 (2f)
PhCH2OH (1a) PhNH2 (2g)
19
19
19
9
10
11
12
13
14
15c
16d
PhCH2OH (1a) 4-OMeC6H4NH2 (2h) 19
PhCH2OH (1a) 3,4-(OMe)2C6H3NH2 19
(2i)
10
PhCH2OH (1a) 3,5-Me2C6H3NH2
(2j)
PhCH2OH (1a) 4-ClC6H4NH2 (2k)
PhCH2OH (1a) 2-BrC6H4NH2 (2l)
PhCH2OH (1a) 1-Naphthyl-NH2
(2m)
PhCH2OH (1a) 2,4,6-Me3C6H2NH2
(2n)
PhCH2OH (1a)
21
91
11
12
13
19
21
21
94
66
76
a Reaction conditions: 5 mol% of Cu(ClO4)2·6H2O, 1.0 mmol of 1a,
1.5 mmol of 2a, 1 mL solvent. b Determined by 1H NMR with N,N-
dicyclohexylmethylamine as an internal standard. c Reaction time was
24 hours. d Reaction time was 48 hours.
14
15
21
22
Trace
92
(2o)
PhCH2NH2 (2a)
PhCH2NH2 (2a)
amount of the imine product (benzyl amine self-coupling
product, Table 1, entry 11).12
16
17
n-Butanol (1b)
1-Dodecanol
(1c)
24
24
Trace
Trace
The effects of the base and its loading were also examined.
Without base, the reaction only afforded the desired imine in
moderate yield (48%, entry 1, Table 2). Slightly increasing the
base loading did not affect the yield at all (Table 2, entries 2 and
3). Appreciable yield (84%, entry 4) was obtained when
100 mol% of KOH was introduced to the reaction conditions. A
slight excess of base further increased the yield of the corre-
sponding imine (entry 5). Other bases, such as K2CO3, NaOH,
KOtBu and DBU, furnished the desired imine in much lower
yields (entries 6–9). Subsequently, the solvent effect was investi-
gated. Toluene is the best solvent here. Other solvents, such as
MeCN, CH2Cl2, THF and MeOH, were also tested and resulted
in the formation of the imine in poor to moderate yields (entries
10–13). The reaction in water only produced a trace amount of
the product whilst virtually all the starting material remained
(entry 14). The reaction was sluggish at room temperature (entry
15), and the yield of product showed no noticeable improvement
even after extending the reaction time to 48 hours (entry 16).
With the optimized reaction conditions in hand, we then
explored the substrate scope and generality of the current metho-
dology and the results are summarized in Table 3. Firstly, differ-
ent aliphatic amines were examined in this system. The reaction
of linear alkyl amine such as n-butyl amine and dodecylamine
with benzyl alcohol went smoothly to afford the desired imine
product in good yield (entries 2 and 3, Table 3). Cyclohexyl
amine afforded a decreased yield (63%, entry 4, Table 3).
However, the alkyl amines with functional groups such as allyl-
amine and propargylamine failed to afford the corresponding
imine products (entries 5 and 6, Table 3) probably due to their
poor stabilities in the reaction conditions. Then a wide range of
18
PhCH2NH2 (2a)
24
Trace
(1d)
a Reaction conditions: 5 mol% of Cu(ClO4)2·6H2O, 1.0 mmol of 1,
1.5 mmol of 2, 1.5 mmol of KOH, 1 mL toluene at 70 °C. b Determined
by 1H NMR with N,N-dicyclohexylmethylamine as an internal standard.
aromatic amines (anilines) were introduced into optimized reac-
tion conditions. In general, we found that the presence of a sub-
stituent with different electronic properties of aniline did not
have significant influence in the formation of the desired imine
products (entries 7–11, Table 3). However, ortho-substituted aro-
matic amines reduced the yields of imines presumably because
of steric hindrance (entries 12 and 13, Table 3). Furthermore,
more steric hindrance in substrate 2n did not produce the desired
imine under optimized reaction conditions (entry 14, Table 3).
For the heterocyclic amines such as 3-aminopyridine, an excel-
lent yield of the corresponding imine was obtained (92%, entry
15, Table 3). A brief examination of the variation of alcohols
was conducted. Unfortunately, no desired imine products were
1
detected by H NMR and GC–MS when aliphatic alcohols such
as n-butanol (1b) and 1-dodecanol (1c) were used as starting
materials. Finally, an attempt to synthesize ketimine by employ-
ing a secondary alcohol (1d) as a substrate under optimized reac-
tion conditions failed (entry 18, Table 3).
To further investigate the efficiency of this catalytic system, a
gram scale reaction was conducted with lower catalyst loading.
With 0.5 mol% of Cu(ClO4)2·6H2O as catalyst, the coupling
This journal is © The Royal Society of Chemistry 2012
Green Chem., 2012, 14, 1016–1019 | 1017

View Online
Table 4 Investigation of catalyst loadinga
Experimental
All the chemicals and solvents were obtained from commercial
sources and used without further purification. Reactions were
monitored by thin-layer chromatography (TLC) carried out on
0.25 mm E. Merck silica gel plates (60F-254) using UV light as
visualizing agent and an ethanolic solution of ammonium moly-
bdate and anisaldehyde and heat as the developing agent. Gas
chromatography–mass spectrometry (GC–MS) analyses were
carried out with Shimadzu GCMS QP2010. NMR spectra were
recorded on a Bruker AV-400 instrument.
1a
Catalyst loading Time
Yield of
Entry (mol L−1
)
R
(x mol%)
(h)
3 (%)b
1
2
3
4
5
6
1
1
2
4
4
4
PhCH2
PhCH2
PhCH2
PhCH2
n-Butyl
Ph
5
0.5
0.05
0.005
0.005
0.005
19
72
72
72
72
72
90
91
95
82
91
92
General procedure: In
a
typical experiment, alcohol
(1.0 mmol), amine (1.50 mmol), Cu(ClO4)2·6H2O (18.5 mg,
5 mol%), KOH (84 mg, 1.5 mmol), N,N-dicyclohexylmethyl-
amine (internal standard, 71 μL, 0.33 mmol) and toluene (1 mL)
were placed in a 10 mL glass tube. The reaction mixture was
stirred under oxygen atmosphere at 70 °C for 19 hours before it
was quenched by NH4Cl (2 mL, sat. aq.). The layers were separ-
ated and the aqueous layer was extracted with EtOAc (3 ×
3 mL). The combined organic layers were washed with brine
(5 mL), dried (Na2SO4) and concentrated in vacuo. The product
a Reaction conditions: 10 mmol of 1a and 15 mmol of 2, 1.5 equivalent
of KOH at 70 °C under O2 atmosphere. b Determined by H NMR with
1
N,N-dicyclohexylmethyl-amine as an internal standard.
reaction of 10 mmol of benzyl alcohol (1a) with 15 mmol of
benzyl amine (2a) was conducted at the same reaction concen-
tration (1.0 mol L−1, entry 2, Table 4). To our delight, the corre-
sponding imine was obtained in 91% yield. This result
encouraged us to set up another reaction with lower catalyst
loading (0.05 mol%) together with an increase of the reaction
concentration (2.0 mol L−1). The reaction worked very well to
afford the imine in 95% yield with full conversion of the starting
material (entry 3, Table 4). To pursue the minimum catalyst
loading in this transformation, the reaction with remarkably low
catalyst loading, 0.005 mol% of Cu(ClO4)2·6H2O, was per-
formed carefully with 0.2 mol benzyl alcohol (4.0 mol L−1) as
starting material. To our surprise, the reaction gave the desired
product in 49% yield in 2 hours (TOF 4900 hour−1). Thereafter,
the yield increased slowly from 49% to 82% along with the
extension of the reaction time to 72 hours (entry 4, Table 4).13
Furthermore, n-butylamine and aniline were also examined
under this low catalyst loading (0.005 mol% of Cu
(ClO4)2·6H2O) reaction condition. The reactions worked well to
afford the desired imines in 91% and 92% yield, respectively
(entries 5 and 6, Table 4).
1
was characterized by GC–MS and H NMR spectroscopy. The
1
yield of product was determined by H NMR spectroscopy and
calculated based on the amount of alcohol.
Acknowledgements
This work is funded by the Institute of Bioengineering and
Nanotechnology (Biomedical Research Council, Agency for
Science, Technology and Research, Singapore).
References
1 (a) R. W. Layer, Chem. Rev., 1963, 63, 489; (b) J. P. Adams, J. Chem.
Soc., Perkin Trans. 1, 2000, 125; (c) W. Tang and X. Zhang, Chem. Rev.,
2003, 103, 3029; (d) S. F. Martin, Pure Appl. Chem., 2009, 81, 195.
2 Selected review: (a) J. K. Whitesell, Acc. Chem. Res., 1985, 18, 280;
(b) F. A. Davis and B.-C. Chen, Chem. Soc. Rev., 1998, 27, 13;
(c) K. A. Jorgensen, Angew. Chem., Int. Ed., 2000, 39, 3558;
(d) J. A. Ellman, T. D. Owens and T. P. Tang, Acc. Chem. Res., 2002, 35,
984; (e) A. E. Taggi, A. M. Hafez and T. Lectka, Acc. Chem. Res., 2003,
36, 10; (f) H. Groeger, Chem. Rev., 2003, 103, 2795; (g) A. Cordova,
Acc. Chem. Res., 2004, 37, 102; (h) B. Lygo and B. I. Andrews, Acc.
Chem. Res., 2004, 37, 518; (i) W. Notz, F. Tanaka and C. F. Barbas III,
Acc. Chem. Res., 2004, 37, 580; ( j) S. J. Connon, Angew. Chem., Int.
Ed., 2006, 45, 3909; (k) E. Skucas, M.-Y. Ngai, V. Komanduri and
M. J. Krische, Acc. Chem. Res., 2007, 40, 1394; (l) A. G. Doyle and E.
N. Jacobsen, Chem. Rev., 2007, 107, 5713; (m) J.-H. Xie and Q.-L. Zhou,
Acc. Chem. Res., 2008, 41, 581; (n) G.-Q. Lin, M.-H. Xu, Y.-W. Zhong
and X.-W. Sun, Acc. Chem. Res., 2008, 41, 831; (o) K.-I. Yamada and
K. Tomioka, Chem. Rev., 2008, 108, 2874; (p) R. G. Arrayas and J.
C. Carretero, Chem. Soc. Rev., 2009, 38, 1940; (q) Y. Wei and M. Shi,
Acc. Chem. Res., 2010, 43, 1005; (r) J. Wang, X. Liu and X. Feng,
Chem. Rev., 2011, 111, 6947.
Conclusions
In this work, aerobic oxidative coupling of an imine from benzyl
alcohol and amines was achieved by employing commercially
available copper catalyst with a remarkably low catalyst loading
(0.005 mol%). The reaction was conducted at atmospheric
pressure of molecular oxygen which is considered as an abun-
dant and green oxidant. Substrate–catalyst ratios up to 20 000
can be employed in this procedure to produce the desired
product in up to 92% yield (TON is 18 400). A board range of
amines including alkyl, aryl and heterocyclic amines could be
tolerated in this practical procedure. Mechanistic studies and a
further extension of this copper-catalyzed aerobic oxidative
coupling method will be reported in due course.
3 (a) A. L. Strecker, Justus Liebigs Ann. Chem., 1850, 75, 27;
(b) A. Hantzsch, Ann. Chem., 1882, 215, 1; (c) P. G. Biginelli, Chim.
Ital., 1893, 23, 360; (d) C. Mannich and W. Krosche, Arch. Pharm.,
1912, 250, 647; (e) I. Ugi, R. Meyr, U. Fitzer and C. Steinbrücker,
Angew. Chem., 1959, 71, 386; (f) N. R. Candeias, F. Montalbano,
P. M. S. D. Cal and P. M. P. Gois, Chem. Rev., 2010, 110, 6169; (g) J. Yu,
F. Shi and L.-Z. Gong, Acc. Chem. Res., 2011, 44, 1156; (h) L.
H. Choudhury and T. Parvin, Tetrahedron, 2011, 67, 8213.
4 (a) F. Kakiuchi, M. Yamauchi, N. Chatani and S. Murai, Chem. Lett.,
1996, 111; (b) T. Fukuyama, N. Chatani, F. Kakiuchi and S. Murai,
J. Org. Chem., 1997, 62, 5647; (c) B. D. Dangel, K. Godula, S. W. Youn,
1018 | Green Chem., 2012, 14, 1016–1019
This journal is © The Royal Society of Chemistry 2012

View Online
B. Sezen and D. Sames, J. Am. Chem. Soc., 2002, 124, 11856;
(d) B. Sezen, R. Franz and D. Sames, J. Am. Chem. Soc., 2002, 124,
13372; (e) L. V. Desai, K. L. Hull and M. S. Sanford, J. Am. Chem. Soc.,
2004, 126, 9542; (f) R. K. Thalji, J. A. Ellman and R. G. Bergman, J.
Am. Chem. Soc., 2004, 126, 7192; (g) S. J. O’Malley, K. L. Tan,
A. Watzke, R. G. Bergman and J. A. Ellman, J. Am. Chem. Soc., 2005,
127, 13496; (h) L. Ackermann, Org. Lett., 2005, 7, 3123.
10 (a) D. Yu and Y. G. Zhang, Proc. Natl. Acad. Sci. U. S. A., 2010, 107,
20184; (b) D. Yu and Y. G. Zhang, Adv. Synth. Catal., 2011, 353, 163;
(c) Y. G. Zhang, L. W. Chen and T. Lu, Adv. Synth. Catal., 2011, 353,
1055; (d) A. Martínez-Asencio, D. J. Ramon and M. Yus, Tetrahedron,
2011, 67, 3140.
11 For a selective review on the Fe-catalyzed organic reactions, see:
(a) C. Bolm, J. Legros, J. Le Paih and L. Zani, Chem. Rev., 2004, 104,
6217; (b) B. D. Sherry and A. Fuerstner, Acc. Chem. Res., 2008, 41,
1500; (c) A. Correa, O. Garcia Mancheno and C. Bolm, Chem. Soc. Rev.,
2008, 37, 1108; (d) R. H. Morris, Chem. Soc. Rev., 2009, 38, 2282;
(e) C.-L. Sun, B.-J. Li and Z.-J. Shi, Chem. Rev., 2011, 111, 1293;
(f) O. Garcia Mancheno, Angew. Chem., Int. Ed., 2011, 50, 2216;
(g) C. Gonzalez-Arellano, K. Yoshida, R. Luque and P. L. Gai, Green
Chem., 2010, 12, 1281.
5 H. Schiff, Justus Liebigs Ann. Chem., 1864, 131, 118.
6 (a) B. Gnanaprakasam, J. Zhang and D. Milstein, Angew. Chem., Int. Ed.,
2010, 49, 1468; (b) M. A. Esteruelas, N. Honczek, M. Oliván, E. Oñate
and M. Valencia, Organometallics, 2011, 30, 2468; (c) L. Jiang, L. Jin,
H. Tian, X. Yuan, X. Yu and Q. Xu, Chem. Commun., 2011, 47, 10833.
7 (a) L. Blackburn and R. J. K. Taylor, Org. Lett., 2001, 3, 1637;
(b) S. Sithambaram, R. Kumar, Y.-C. Son and S. L. Suib, J. Catal., 2008,
253, 269; (c) M. S. Kwon, S. Kim, S. Park, W. Bosco, R. K. Chidrala
and J. Park, J. Org. Chem., 2009, 74, 2877; (d) H. Sun, F.-Z. Su, J. Ni,
Y. Cao, H.-Y. He and K.-N. Fan, Angew. Chem., Int. Ed., 2009, 48, 4390;
(e) J. W. Kim, J. He, K. Yamaguchi and N. Mizuno, Chem. Lett., 2009,
920; (f) R. Cano, D. J. Ramón and M. Yus, J. Org. Chem., 2011, 76,
5547; (g) Y. Shiraishi, M. Ikeda, D. Tsukamoto, S. Tanaka and T. Hiraia,
Chem. Commun., 2011, 47, 4811; (h) S. Kegnæs, J. Mielby,
U. V. Mentzel, C. H. Christensen and A. Riisager, Green Chem., 2010,
12, 1437.
8 (a) S. Enthaler, K. Junge and M. Beller, Angew. Chem., Int. Ed., 2008,
47, 3317; (b) E. Nakamura and K. Sato, Nat. Mater., 2011, 10, 158.
9 For a selective review on the Cu-catalyzed organic reactions, see:
(a) A. Alexakis, J. E. Backvall, N. Krause, O. Pamies and M. Dieguez,
Chem. Rev., 2008, 108, 2796; (b) L. M. Stanley and M. P. Sibi, Chem.
Rev., 2008, 108, 2887; (c) M. Meldal and C. W. Tornoe, Chem. Rev.,
2008, 108, 2952; (d) F. Collet, C. Lescot and P. Dauban, Chem. Soc. Rev.,
2011, 40, 1926; (e) Y. Liu and J.-P. Wan, Org. Biomol. Chem., 2011, 9,
6873.
12 It should be noted that only a trace amount of imine could be detected
under the optimized conditions without benzyl acohol as substrate. For
self-condensation of primary amine with oxidant to afford imine, see:
(a) K. Orito, T. Hatakeyama, M. Takeo, S. Uchiito, M. Tokuda and
H. Suginome, Tetrahedron, 1998, 54, 8403; (b) A. H. Ėll,
J. S. M. Samec, C. Brasse and J.-E. Bäckvall, Chem. Commun., 2002,
1144; (c) S. M. Landge, V. Atanassova, M. Thimmaiah and B. Török, Tet-
rahedron Lett., 2007, 48, 5161; (d) M. Largeron, A. Chiaroni and
M. B. Fleury, Chem.–Eur. J., 2008, 14, 996; (e) C. S. Yi and D. W. Lee,
Organometallics, 2009, 28, 947; (f) G. Chu and C. Li, Org. Biomol.
Chem., 2010, 8, 4716; (g) A. Berlicka and B. König, Photochem. Photo-
biol. Sci., 2010, 9, 1359; (h) A. Dhakshinamoorthy, M. Alvaro and
H. Garcia, ChemCatChem, 2010, 2, 1438; (i) S. Kodama, J. Yoshida,
A. Nomoto, Y. Ueta, S. Yano, M. Ueshima and A. Ogawa, Tetrahedron
Lett., 2010, 51, 2450; ( j) A. Corma, T. Ródenas and M. J. Sabater,
Chem.–Eur. J., 2010, 16, 254.
13 The yield of reaction was tracked by 1H NMR: 2 hours (49%), 24 hours
(76%), 48 hours (81%) and 72 hours (82%), respectively.
This journal is © The Royal Society of Chemistry 2012
Green Chem., 2012, 14, 1016–1019 | 1019