Table 2 Etherification reactions of para-substituted benzyl alcohol derivativesa
Entry
Catalyst
Y
IL
Yield (%) (1)b
Time (min)/Temp (1C)
1
2
3
4
5
6
7
8
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Recycle 1 (reuse entry 4)
Recycle 2 (reuse entry 5)
Pd(CH3CN)2Cl2
H
Cl
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[BMIm]PF6
[P66614]DBS
[P66614]DBS
[BMMIm]PF6
55
55
57
71
96
78
0
6
8
8
0
7/140
10/145
12/114
9/113
CH3
OCH3
OCH3
OCH3
NO2
Br
2 ꢃ 15/106
8/116
10/115
12/170
11/131
10/115
10/58c
24 h/90d
6/140
Pd(CH3CN)2Cl2
9
Pd cat. precipitate
Pd(CH3CN)2Cl2/CuCl2ꢂ2H2O
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
Cl
10
11
12
13
CH3
OCH3
OCH3
H
56
50
a
b
c
For reaction conditions, see Table 1 footnote a. Yields were calculated using 1H-NMR spectroscopy (for more information see ESIw). Using
same MW power settings as other reactions. At the highest power setting, 9 minutes were needed to achieve 108 1C and this temperature could only
be held safely for 2 minutes. Yield of (1) and conversion of BnOH was 0. Reaction mixture was heated in an oil bath due to lower dielectric
heating using [P66614]DBS.
d
31P-NMR experiments also confirmed the presence of F and P (Fig. S2
and S3, ESIw). Attempts to use the precipitate as a catalyst (as it
contained Pd) were made. It was separated, dried and used (Table 2,
entry 9), but the yield was low.
y 4, 5 and 6 (and their analogues) were not observed by GC-MS upon
extracting samples from other reaction mixtures (Tables 1 and 2) and
analysing under the same conditions. Furthermore, GC calibration
samples of alcohols and ethereal products did not show 4, 5 and 6.
Therefore, it is highly unlikely that 4, 5 and 6 were formed within the
GC-MS instrument and indeed did form during the microwave-
assisted catalytic reactions.
1 K. Manabe, S. Iimura, X.-M. Sun and S. Kobayashi, J. Am. Chem.
Soc., 2002, 124, 11971.
2 (a) E. A. Schmittling and J. S. Sawyer, J. Org. Chem., 1993, 58,
3229; (b) J. C. Lee, J. Choi and J. S. Lee, Bull. Korean Chem. Soc.,
2004, 25, 1117.
Fig. 1 Byproducts formed upon prolonged heating of reaction
mixtures.
3 (a) G. D. Yadav and O. V. Badure, Ind. Eng. Chem. Res., 2007, 46,
8448; (b) D. H. Hwu, C. Hwang, Y. P. Shih, M. Y. Yeh and
reactions using PdCl2 rather than Pd(CH3CN)2Cl2. 4 and 6
were observed as the main products (Fig. S6, S7 and S8,
ESIw).y This demonstrates that acetonitrile is required and
probably coordinated to the Pd in order to give control to the
etherification reactions.
C. L. Chao, Ind. Eng. Chem. Res., 1992, 31, 177.
4 (a) V. D. Sarca and K. K. Laali, Green Chem., 2006, 8, 615;
(b) A. Corma and M. Renz, Angew. Chem., Int. Ed., 2007, 46, 298;
(c) G. V. M. Sharma and A. K. Mahalingam, J. Org. Chem., 1999,
64, 8943.
5 (a) V. V. Namboodiri and R. S. Varma, Tetrahedron Lett., 2002,
43, 4593; (b) J. S. Sawyer, Tetrahedron, 2000, 56, 5045;
(c) J. Muzart, Tetrahedron, 2008, 64, 5815.
6 (a) S. Bouquillon, F. Henin and J. Muzart, Organometallics, 2000,
19, 1434; (b) C. A. Parrish and S. L. Buchwald, J. Org. Chem.,
2001, 66, 2498; (c) M. C. Willis, D. Taylor and A. T. Gillmore,
Chem. Commun., 2003, 2222.
In summary, we have shown that Pd(CH3CN)2Cl2 in a
hydrophobic ionic liquid affords a simple catalytic system
for the direct condensation of substituted benzyl alcohols to
afford their corresponding ethers. In the presence of NH4Cl,
benzyl chloride can be obtained in excellent yield. Although
some clues about the mechanism for both reactions have been
obtained, e.g. the absence of colloids and N-heterocyclic
carbene species, the role of the ionic liquid, metal and ligands
and the reaction pathway are still under investigation.
We acknowledge support from NSERC of Canada and the
Canada Foundation for Innovation in the form of a Discovery
Grant, a Research Tools and Instrument Grant, an Under-
graduate Summer Research Award (C.F.P.) and a Leaders
Opportunity Fund Award (F.M.K.). We would also like to
thank Cytec Industries Inc. for samples of [P66614]DBS and
Memorial University for funding.
7 J. Muzart, Tetrahedron, 2005, 61, 5955.
8 (a) P. Wasserscheid and T. Welton, Ionic Liquids in Synthesis,
VCH, Weinheim, 2007; (b) T. Welton, Coord. Chem. Rev., 2004,
248, 2459; (c) N. V. Plechkova and K. R. Seddon, Chem. Soc. Rev.,
2008, 37, 123; (d) F. M. Kerton, Alternative Solvents for Green
Chemistry, RSC Publishing, Cambridge, 2009.
9 (a) S. M. S. Chauhan, N. Jain, A. Kumar and K. A. Srinivas,
Synth. Commun., 2003, 33, 3607; (b) Y. Luo, J. X. Wu and
R. X. Ren, Synlett, 2003, 1734.
10 (a) S. V. More, S. S. Ardhapure, N. H. Naik, S. R. Bhusare,
W. N. Jadhav and R. P. Pawar, Synth. Commun., 2005, 35, 3113;
(b) F. Mohanazadeh and M. Aghvami, Monatsh. Chem., 2007, 138,
47.
11 For example, X. Zhang and A. Corma, Dalton Trans., 2008, 397.
12 (a) T. Giacco, A. Faltoni and F. Elisei, Phys. Chem. Chem. Phys.,
Notes and references
2008, 10, 200; (b) M. Salmo
R. Gavino, R. Miranda and M. Martı
1995, 104, L127.
n, N. Zavala, A. Cabrera, J. Cardenas,
´ ´
´
nez, J. Mol. Catal. A: Chem.,
z EDX (energy dispersive X-ray) analysis of the precipitate showed the
presence of Pd, F, Si, P and Na (Fig. S1, ESIw). Solid-state 19F and
ꢁc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5171–5173 | 5173