Microwave-assisted preparation of dialkylimidazolium tetrachloroaluminates and their use as catalysts in the solvent-free tetrahydropyranylation of alcohols and phenols

Article abstract of DOI:10.1039/b110565e

Microwave-assisted preparation of dialkylimidazolium tetrachloroaluminates, [C_nMIM][A1C1₄] and their application as recyclable catalysts for the efficient and eco-friendly protection of alcohols as tetrahydropyranyl (THP) ethers are described. The same catalyst can also be utilized for the deprotection of THP ethers.

Full text of DOI:10.1039/b110565e

Microwave-assisted preparation of dialkylimidazolium
tetrachloroaluminates and their use as catalysts in the solvent-free
tetrahydropyranylation of alcohols and phenols
Vasudevan V. Namboodiri and Rajender S. Varma*
Clean Processes Branch, National Risk Management Research Laboratory, U.S. Environmental Protection
Agency, MS 443, 26 W. Martin Luther King Drive, Cincinnati, OH 45268, USA.
E-mail: Varma.Rajender@epa.gov
Received (in Corvallis, OR, USA) 16th November 2001, Accepted 10th December 2001
First published as an Advance Article on the web 23rd January 2002
Microwave-assisted preparation of dialkylimidazolium
tetrachloroaluminates, [CnMIM][AlCl4] and their applica-
tion as recyclable catalysts for the efficient and eco-friendly
protection of alcohols as tetrahydropyranyl (THP) ethers are
described. The same catalyst can also be utilized for the
deprotection of THP ethers.
Room temperature ionic liquids (RTILs) consisting of N-
alkylimidazolium cations1 and various anions, have received
wide attention due to their potential in a variety of commercial
Scheme 1
applications such as electrochemistry,2 heavy metal ion extrac-
tion,3 phase transfer catalysis and polymerization,4 and as
substitutes for conventional volatile organic solvents.5 They are
The ionic liquids with tetrachloroaluminate anion are sig-
polar but consist of poorly coordinating ions and provide a polar
alternative for biphasic systems. Other important attributes of
these ionic liquids include negligible vapor pressure, potential
for recycling, compatibility with various organic compounds
and organometallic catalysts,6 and ease of separation of
products from reactions.
nificant for several synthetic applications, especially Friedel-
Crafts reaction where they can be good substitutes for the
conventional highly toxic and corrosive reagents such as HF or
AlCl3, which are consumed in large quantity and consequently
generate a large amount of contaminated waste. The reported
methods for the preparation of these salts are time consuming10
and we have extended our microwave heating protocol to the
preparation of tetrachloroaluminates (Table 1).
A recently introduced household MW oven (Panasonic)
equipped with inverter technology provides a realistic control of
the microwave power to a desirable level.8 Microwave heating
provides a more uniform heating of this highly viscous medium
and is also faster than the corresponding conventional heating.
A mixture of alkylimidazolium chloride and aluminum chloride
is mixed using a vortex mixer and heated in the MW oven when
the solid aluminum chloride phase slowly disappears and the
complete conversion results in a clear single phase.†
Table 1 provides the optimized reaction conditions for
obtaining pure products using three N,N’-dialkylimidazolium
chlorides (1-butyl-3-methylimidazolium chloride [C4MIM]Cl
and the corresponding hexyl [C6MIM]Cl and octyl chlorides
[C8MIM]Cl). The NMR data of the products are in conformity
with the structure. The TGA and DSC data show that all these
ionic salts are pure and are free of any starting materials.
In view of the emerging importance of the ionic liquids as
reaction media7 and our general interest in microwave-assisted
chemical processes,8,9 we decided to explore the synthesis of
ionic liquids bearing tetrachloroaluminate anions using micro-
wave (MW) irradiation under solvent-free conditions. Ionic
liquids, being polar and ionic in character, couple to the MW
irradiation very efficiently and consequently may be ideal
microwave absorbing entities for expediting chemical manip-
ulations. An efficient preparation of the 1,3-dialkylimidazolium
halides via microwave heating has been described that reduces
the reaction time from several hours to minutes and avoids the
use of a large excess of alkyl halides/organic solvents as the
reaction medium.8 Herein, we report an efficient method for the
preparation of ionic salts that involves exposing N, NA-
dialkylimidazolium chloride and aluminum chloride to micro-
waves in an unmodified household MW oven. This solvent-free
approach, again, requires only a few minutes of reaction time in
contrast to several hours needed under conventional heating
conditions.10 A schematic representation for the preparation of
[CnMIM][AlCl4] is shown in Table 1.
Table 1 Preparation of [CnMIM][AlCl4] using microwavea
The tetrahydropyranyl (THP) protection and deprotection of
alcohols is one of the most frequently employed methods in
multi-step organic syntheses.11 The THP ethers are attractive
for the reason that they are less expensive, easy to deprotect and
are stable enough to strong basic media, oxidative conditions,
reduction with hydrides, and reactions involving Grignard
reagents, lithium alkyls and alkylating and acylating reagents.
There are several processes available in the literature for these
protection–deprotection sequences12 but most of these methods
require a high catalyst to substrate ratio, have a long reaction
time and involve the use of volatile organic solvents or large
amounts of solid supports, which eventually result in generation
of a large amount of toxic waste. Thus, there is a need for a
solvent-free and catalytically efficient alternative for the
protection and deprotection of hydroxy functionality as THP
ether. Herein, we report an efficient solvent-free tetrahydropyr-
anylation of alcohols and phenols catalyzed by [CnMIM]-
[AlCl4] (Scheme 1).
where R = butyl, hexyl or octyl
Ionic liquid (3
mmol)
MW-Power
(Watts)
Time (s)
Yield (%)
[C4MIM]Cl
240
360
480
480
360
480
360
480
30+30+30+30+30+30+30
30+30+30+30+30+30+30
30+15+15+15+15+15+15
60+30+30+30+30+30+30
30+30+30+30+30+30+30
30+15+15+15+15+15+15
30+30+30+30+30+30+30
30+30+15+15+15+15+15
100b
100
100
100c
100
100
100
100
[C6MIM]Cl
[C8MIM]Cl
a AlCl3.6H2O (3 mmol). b Traces of unreacted aluminum chloride found.
c [C4MIM]Cl (20 mmol, AlCl3.6H2O (20 mmol).
342
CHEM. COMMUN., 2002, 342–343
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vimetric analysis (TGA) of the samples were performed by heating from 25
The use of these ionic liquids as recyclable catalysts has been
explored in the protection and deprotection sequence for
alcohols as THP-ethers using [C4MIM]AlCl4 as a model
catalyst (Table 2). It is apparent that the MW-generated
tetrachloroaluminate salts are efficient catalysts in tetra-
hydropyranylation of alcohols and deprotection of THP ethers
and can be utilized as such without further purification. A wide
variety of hydroxylated compounds were rapidly converted to
the corresponding THP ethers via this procedure at rt. It is
important to note that an acid sensitive alcohol like tert-butanol
(entry 5, Table 2) undergoes protection as tetrahydropyranyl
ether without the formation of a dehydration product. Another
important feature of this method is the efficient mono-
tetrahydropyranylation of 1,n-diols (entry 7, Table 2), a
transformation that is difficult to accomplish via conventional
methods. The NMR studies on the THP ethers are in conformity
with the corresponding literature reports.12
to 500 °C at a rate of 10 °C min21 and differential scanning calorimetric
analysis (DSC) was conducted from 25 to 450 °C at a heating rate of 10 °C
21min. An unmodified household microwave (MW) oven, Panasonic NN-
S740WA-1200W, was used for heating.
[C4MIM]AlCl4. In a typical method, aluminum chloride hexahydrate
(3.0 mmol) and 1-butyl-3-methylimidazolium chloride (3.0 mmol) were
placed in a glass test tube and mixed thoroughly on a vortex mixer. The
mixture was heated in the MW oven at 360 W (30 s irradiation with 10 s
mixing) until the dissolution of aluminum crystals was completed and
resulted in the formation of a single phase (Table 1). The bulk temperature
recorded was in the range 80 to 110 °C. The resulting ionic liquid was then
dried under vacuum at 80 °C to afford [C4MIM][AlCl4]. The same
experiment via conventional heating (oil bath at 90 °C for 3 h) resulted only
in impure product. An experiment on a relatively large scale starting from
20 mmol of aluminum chloride hexahydrate and 20 mmol of [C4MIM]Cl
also afforded [C4MIM]AlCl4 (20.0 mmol, mp 65 °C). 1H NMR (250 MHz;
D2O), dH: 0.72(t, CH3), 1.15(m, CH2), 1.81(m, CH2), 3.71(s, N-CH3), 4.09
(m, N-CH2), 7.38(s, NCH), 7.43 (s, NCH), 8.7 (s, N(H)CN); 13C NMR dC
12.89 (t, CH2), 19.02 (m, CH3), 31.51 (m, CH2), 35.86 (N-CH2), 49.51(N-
CH3), 122.40 (NCH), 123.73 (NCH), 136.21 (N(H)CN).
Table 2 Tetrahydropyranylation of alcohols in presence of [C4MIM]Al-
ab
Cl4
Tetrahydropyranyl ether. In a typical procedure, benzyl alcohol (100
mmol) and 3,4-dihydro-2H-pyran (110 mmol) were added to [C4MI-
M]AlCl4 (1 mmol) prepared earlier and then stirred with a magnetic stirring
bar. The progress of the reactions was followed using GC-MS. The
disappearance of the alcohol signal in the GC determined the completion of
reaction and the product was extracted with ether and filtered through a
silica column (2 cm length) to remove any ionic impurities. The residual
3,4-dihydropyran and solvent were removed on a rotary evaporator
followed by vacuum drying to afford THP ether (98%). In the case of diol
(entry 7, Table 2), further purification was accomplished by filtering it
through a short silica column (eluted with petroleum ether). For recycling
studies, the ionic liquid separated after product extraction into diethyl ether,
was dried and reused (entry 9, Table 2).
Yields %
Temperature GC
Time
(min)
Entry
Alcohol
(°C)
(isolated)
1
2
3
4
5
6
7
8
9
1-Hexanol
Cyclohexanol
Phenol
2-Naphthol
tert-Butanol
3-Methyl-2-buten-1-ol
1,2-Ethanediol
Benzyl alcohol
Benzyl alcohol
15
15
10
30
15
15
30
15
15
25
25
25
50
25
25
25
25
25
100(95)
100(96)
100(97)
100(95)
100(95)
100(98)
76(74)
100(98)
100(96)c
Detetrahydropyranylation of THP ethers. THP ether (100 mmol),
[C4MIM]AlCl4 (1 mmol) and excess methanol (800 mmol) were mixed
together at rt for 30 min affording complete regeneration of the alcohol. The
cleavage of THP ethers and regeneration of alcohols were similarly
followed by GC.
a [C4MIM]AlCl4 (1 mmol) and 3,4-dihydropyran (110 mmol) and alcohol
(100 mmol). b For complete detetrahydropyranylation at rt: THP ether (100
mmol), [C4MIM]AlCl4 (1 mmol) and methanol (800 mmol), 30 min. c Yield
after 4 recycles.
1 T. Welton, Chem. Rev., 1999, 99, 2701.
2 J. S. Wilkes, J. A. Levinsky, R. A. Wilson and C. L. Hussey, Inorg.
Chem., 1982, 21, 1263.
3 A. E. Visser, R. P. Swatloski and R. D. Rogers, Green Chemistry, 2000,
2, 1; A. E. Visser, R. P. Swatloski, W. M. Reichert, R. D. Rogers, R.
Mayton, S. Sheff, A. Wierzbicki and J. H. Davis Jr., Chem. Commun.,
2001, 135.
4 A. J. Carmichael, D. M. Haddleton, S. A. F. Bon and K. R. Seddon,
Chem. Commun., 2000, 1237.
5 J. S. Wilkes and M. J. Zaworotko, J. Chem. Soc., Chem. Commun.,
1992, 965.
6 J. D. Holbrey and K. R. Seddon, Clean Products and Processes, 1999,
1, 223; J. G. Huddleston, H. D. Willauer, R. P. Swatloski, A. E. Visser
and R. D. Rogers, Chem. Commun., 1998, 1765.
7 M. Freemantle, Chem. Eng. News, 1 January, 2001, p. 21; M.
Freemantle, Chem. Eng. News, 15 May, 2000, p. 37.
8 R. S. Varma and V. V. Namboodiri, Chem. Commun., 2001, 643; R. S.
Varma and V. V. Namboodiri, Pure Appl. Chem., 2001, 73, 1309.
9 R. S. Varma, in Green Chemical Syntheses and Processes, ed. P. T.
Anastas, L. G. Heine and T. C. Williamson, ACS Symposium Series
767, American Chemical Society, Washington, D.C., 2000, pp.
292–312; R. S. Varma, J. Heterocyclic Chem., 1999, 35, 1565; R. S.
Varma, Green Chemistry, 1999, 1, 43; R. S. Varma, Pure Appl. Chem.,
2001, 73, 193.
10 J. G. Huddleston, A. E. Visser, W. M. Reichert, H. D. Willauer, G. A.
Brocker and R. D. Rogers, Green Chemistry, 2001, 3, 156.
11 T. W. Greene and P. G. M. Wuts, Protective Groups in Organic
Synthesis, 2nd edn., John Wiley & Sons, Inc., New York, 1999.
12 T. Nishiguchi, S. Fujisaki, M. Kuroda, K. Kajisaki and M. Saitoh, J.
Org. Chem., 1998, 63, 8183; N. Deka and J. C. Sarma, J. Org. Chem.,
2001, 66, 1947; T. C. Turek, I. Gaon, M. D. Distefano and C. L. Strick,
J. Org. Chem., 2001, 66, 3256; G. A. Olah, A. Husain and B. P. Singh,
Synthesis, 1983, 892; S. Hoyer, P. Laszlo, M. Orlovic and E. Polla,
Synthesis, 1986, 655; B. C. Ranu and M. Saha, J. Org. Chem., 1994, 59,
8269.
The tetrahydropyranylation reactions with tetrachloroalumi-
nate salts do not require absolute anhydrous conditions. The
ionic liquid catalyst is recovered for further use by simply
extracting the products with diethyl ether, which forms a
separate layer and can be conveniently decanted off. The
recycling study with ionic liquid catalyst reveals that the
catalyst can be recycled without much loss of reactivity (entry
9, Table 2), which we checked up to 4 recycles. The complete
deprotection of the alcohols is achieved via a metathesis
reaction with excess methanol using the same catalyst.
In conclusion, a solvent-free MW-assisted protocol is
developed for the synthesis of 1,3-dialkylimidazolium tetra-
chloroaluminates using an unmodified household microwave
oven, a method that precludes the usage of volatile organic
solvents and is relatively much faster, efficient, and eco-
friendly. The general use of these ionic liquids in the protection
and deprotection of alcohols is demonstrated in the tetra-
hydropyranylation reaction. We envisage that this method will
find practical application for the protection and deprotection of
alcohols in modern synthetic chemistry.
VVN is a postgraduate research participant at the National
Risk Management Research Laboratory administered by the
Oak Ridge Institute for Science and Education.
Notes and references
† 1-Methylimidazole (MIM) and alkyl halides were obtained from Aldrich
Chemical company and were used as such. 1,3-Dialkylimidazolium
chlorides were prepared using microwave as reported earlier.8 The NMR
spectra of the samples were recorded on a Brucker 250 MHz spectrometer
using D2O as solvent and CD3OD/CDCl3 as the standards. The thermogra-
CHEM. COMMUN., 2002, 342–343
343