Microwave-assisted preparation of imidazolium-based tetrachloroindate(III) and their application in the tetrahydropyranylation of alcohols

Article abstract of DOI:10.1016/j.tetlet.2005.01.025

Microwave-assisted preparation of 1-alkyl-3-methylimidazolium tetrachloroindate(III), [Rmim][InCl₄] (R = methyl, ethyl, butyl, hexyl, octyl) and their application as recyclable catalysts for the efficient and eco-friendly protection of alcohols to form tetrahydropyranyl (THP) ethers are described.

Full text of DOI:10.1016/j.tetlet.2005.01.025

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1467–1469
Microwave-assisted preparation of imidazolium-based
tetrachloroindate(III) and their application in the
tetrahydropyranylation of alcohols
Yong Jin Kim and Rajender S. Varma*
Sustainable Technology Division, National Risk Management Research Laboratory, US Environmental Protection Agency,
26W. Martin Luther King Dr., MS 443, Cincinnati, OH 45268, USA
Received 18 November 2004; revised 6 January2005; accepted 7 January2005
Available online 23 January2005
Abstract—Microwave-assisted preparation of 1-alkyl-3-methylimidazolium tetrachloroindate(III), [Rmim][InCl4] (R = methyl,
ethyl, butyl, hexyl, octyl) and their application as recyclable catalysts for the efficient and eco-friendly protection of alcohols to form
tetrahydropyranyl (THP) ethers are described.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
velop solventless chemical transformations using MW,6
herein we report expeditious preparation of 1-alkyl-3-
methylimidazolium tetrachloroindate(III) compounds
using MW irradiation, which are subsequentlyutilized
in the tetrahydropyranylation of alcohols.
Room temperature ionic liquids (RTILs), especially
those based on the 1-alkyl-3-methylimidazolium cation,
are attracting increasing interest as new reaction media
in manyorganic transformations, as electrolytes for bat-
teries and capacitors, and in separation processes,
mainlybecause of their advantageous nonvolatile nature
2. Results and discussion
1
and their easilytunable phsyicochemical properties.
Ionic liquids have been developed for task-specific pur-
poses, however, a large majorityof those studies have
focused on the use of ILs as reaction media.2 More re-
cently, there have been increasing efforts to utilize ILs
as active catalysts for the organic synthesis.3 Among
ionic liquids in this context, we are particularlyinter-
ested in the imidazolium-based RTILs containing chloro-
indate(III), which exhibit Lewis acid properties similar
to those of chloroaluminate ILs without being reactive
toward air and water, which is generallyconsidered to
be a main limitation.4
Admixing equimolar amounts of indium trichloride and
solid 1-butyl-3-methylimidazolium chloride, followed by
MW irradiation for 30 s (15 s · 2 times) without anysol-
vent afforded a crude mixture of liquid and small quan-
tityof unreacted InCl 3, which was removed byfiltration
to afford colorless single phased liquid (Scheme 1). This
liquid product was fullycharacterized as [C 4mim][InCl4]
(C4mim = 1-butyl-3-methylimidazolium) by NMR spec-
troscopyand TGA analysis. It was found that MW irra-
diation provided a more uniform heating of this viscous
medium and the reaction proceeded much faster than
the corresponding protocol using conventional heating.
Table 1 shows the optimized reaction conditions for
the preparation of the pure [Rnmim][InCl4] using five
A recentlyintroduced household microwave (MW) oven
(Panasonic) equipped with inverter technologyprovides
a realistic control of the microwave power to a desirable
level.5 As a part of an ongoing research program to de-
Cl
InCl4
R
R
N
N
InCl3
+
N
N
MW
Keywords: Microwave irradiation; Ionic liquid; Tetrahydropyranyl-
ation; Imidazolium-based tetrachloroindate.
R = methyl, ethyl, butyl, hexyl, octyl
*
Corresponding author. Tel.: +1 513 487 2701; fax: +1 513 569
7677; e-mail: varma.rajender@epa.gov
Scheme 1.
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.025

1468
Table 1. Preparation of [Rnmim][InCl4] using MWa
EntryIonic liquid Time (s) Yield (%)
93
Y. J. Kim, R. S. Varma / Tetrahedron Letters 46 (2005) 1467–1469
Table 2. MW-assisted tetrahydropyranylation of alcohols in the
presence of [C4mim][InCl4]a
EntryAlcohol
Time (min)
5
Yields (%)
GC (isolated)
1
2
3
4
5
[C1mim]Cl
15+15
[C2mim]Cl
[C4mim]Cl
[C6mim]Cl
[C8mim]Cl
15+15
15+15
94
93
90
89
1
2
3
88 (82)
OH
15+15+15+15
15+15+15+15
60b
5
60b
20b
a Conditions: ionic liquid (5 mmol), InCl3 (5.0 mmol), MW power
(600 W).
85 (79)
39b
OH
OH
different imidazolium halides, [Rnmim]Cl (Rn = methyl
(C1), ethyl (C2), butyl (C4), hexyl (C6), octyl (C8)). The
NMR spectra of the ionic liquids obtained from MW
reactions are in conformitywith the structure.
10
5
o: 52
m: 70
p: 72
H3C
5
4
5
5
84
HO
Tetrahydropyranylation is one of the most frequently
employed methods for the protection of hydroxyl
groups in multi-step organic synthesis.7 The tetrahydro-
pyranyl (THP) ethers are attractive because they are less
expensive and are stable enough to strong basic media,
oxidative conditions, reduction with hydrides, reactions
involving Grignard reagents, etc. There are several pro-
cesses available in the literature for the preparation of
THP-ethers but majorityof them have a long reaction
time and involve the use of volatile organic solvents or
large amounts of solid supports, which eventuallyleads
to generation of a large amount of toxic waste. There-
fore, there is a need for a solvent-free and efficient alter-
native for the protection of hydroxyl compounds
(Scheme 2).
OH
10
77 (70)
OH
6
7
8
5
10
5
86 (79)
65
OH
86c
OH
a Conditions: 3,4-dihydropyran (11 mmol), alcohol (10 mmol),
[C4mim][InCl4] (2.5 mmol).
b Conventional heating at 60 ꢁC.
c Yield after five recycles.
The tetrahydropyranylations of various alcohols were
carried out using 25 mol % of [C4mim][InCl4] as a model
catalyst at 60 ꢁC, 100 W of MW power (CEM system).
As shown in Table 2, the conventional heating (60 ꢁC,
1 h) afforded only20% and 39% yields of corresponding
THP-ethers from phenol and benzyl alcohol, respec-
tively(entries 1 and 2). When the same reaction was con-
ducted under MW irradiation conditions in the presence
of [C4mim][InCl4], the yields of products increased to
88% and 85% within 5 min, respectively. The protection
methodologywas successful for a varietyof substrates
with a range of functional groups, providing fairlygood
yields of THP-ether. However, the o-cresol (entry3)
produced the product in only52% yield, probablydue
to the steric effect of ortho position of methyl group.
The effect of the change of alkyl group appended to
the imidazolium cation was found to be less pronounced
in the activity, giving similar yields to that of model cata-
lyst, [C4mim][InCl4] in the tetrahydropyranylation of
benzyl alcohol.
separate layer and can be conveniently decanted off, fol-
lowed byfresh charge of reactants in the same reaction
vessel. The recycling study with the ionic liquid catalyst
reveals that the catalyst can be recycled several times
without much loss of its reactivity(entry8, after five
cycles).
3. Conclusion
In conclusion, a solvent-free MW-assisted protocol is
developed for the synthesis of 1-alkyl-3-methylimidazo-
lium tetrachloroindate(III) using an unmodified house-
hold microwave oven. The use of these ionic liquids in
the MW-assisted protection of alcohols is demonstrated
in the tetrahydropyranylation that precludes the use of
volatile organic solvents. Furthermore, these ionic liquid
catalysts can be effectively recycled, thus rendering this
expeditious protection protocol more efficient and eco-
friendly.
To investigate the possibility of recycling the catalyst,
the [C4mim][InCl4] is recovered for further use bysimply
extracting the products with diethyl ether, which forms a
4. Preparation of [1-butyl-3-methylimidazolium][InCl4]—
general procedure
In a typical method, indium trichloride (5.0 mmol) and
1-butyl-3-methylimidazolium chloride (5 mmol) were
placed in a glass test tube and mixed on a vortex mixer.
The mixture was subjected to the MW irradiation at
600 W (two times for 15 s irradiation) in Panasonic
household MW oven until these solid mixtures resulted
MW
R'OH
+
[Rmim][InCl4]
O
O
OR'
R = methyl, ethyl, butyl, hexyl, octyl
Scheme 2.

Y. J. Kim, R. S. Varma / Tetrahedron Letters 46 (2005) 1467–1469
1469
in a crude mixture of liquid and a small quantityof
unreacted InCl3, which was filtered using a syringe filter
to afford colorless single phased liquid. This liquid was
fullycharacterized byNMR spectroscopyand TGA
analysis. The bulk temperature recorded was in the
range 60–80 ꢁC. The same experiment via conventional
heating (glycerol bath at 70 ꢁC for 1 h) resulted onlyin
73% yield. An experiment on a relatively large scale
starting from 30 mmol of indium trichloride and
30 mmol of [C4mim]Cl afforded the same product (yield:
Research Laboratory, US Environmental Protection
Agency.
References and notes
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1
93%; mp: À6 ꢁC). H NMR (300 MHz, D2O, 25 ꢁC): d
0.81 (t, 3J(H,H) = 7.2 Hz, 3H, CH3); 1.19 (m, 2H,
CH2); 1.72 (m, 2H, CH2); 3.79 (s, 3H, NCH3); 4.09 (t,
3J(H,H) = 7.6 Hz, 2H, NCH2); 7.30 (d, 3J(H,H) =
1.5 Hz, 2H, C3H3N2); 8.58 (s, 1H, C3H3N2). 13C NMR
(300 MHz, D2O, 25 ꢁC): d 12.6 (CH3); 18.7 (CH2);
31.2 (CH2); 35.7 (NCH3); 49.3 (NCH2); 122.2
(C3H3N2); 123.5 (C3H3N2); 135.8 (C3H3N2).
5. Tetrahydropyranyl (THP) ethers—general procedure
The experimental set-up for the MW experiment was the
commerciallyavailable ÔDiscover Focused Microwave
Synthesis SystemÕ from CEM Corporation, with a
proper temperature and a pressure control.8 In a typical
procedure, a mixture of benzyl alcohol (10 mmol), 3,4-
dihydro-2H-pyran (11 mmol), and [C4mim][InCl4]
(2.5 mmol) was charged in a round-bottom glass flask
(50 mL) containing a magnetic stirring bar and a reflux
condenser. The flask was placed in the microwave cav-
ity, which is designed to house a round-bottom flask.
The flask was subjected to MW irradiation at 60 ꢁC
(power 100 W) for a specified period. After completion
of the reaction, the flask was removed and cooled to
room temperature. The progress of the reaction was fol-
lowed using GC–MS and the disappearance of the signal
for the starting alcohol in the GC determined the com-
pletion of reaction. The product was extracted with
ether and filtered through the short silica column to re-
move anyimpurities. The residual 3,4-dihydro-2 H-pyr-
an and solvent were removed on a rotaryevaporator
followed byvacuum drying to afford THP-ether (79%
yield).
Acknowledgements
We wish to thank Tom Deinlein, Julius Enriquez, Albert
Foster, and AmyZhao for their assistance. This re-
search was performed while the author held a National
Research Council Research Associateship Award at
Clean Processes Branch, National Risk Management
7. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 2nd ed.; John Wiley& Sons Inc.:
New York, 1999.
8. Kim, Y. J.; Varma, R. S. Tetrahedron Lett. 2004, 45,
7205.