Room-temperature ionic liquid-promoted Williamson's synthesis of ethers: A facile synthesis of diaryloxymethanes

Article abstract of DOI:10.1080/00397910500281267

A simple and efficient method has been developed for the synthesis of phenolic ethers using room-temperature ionic liquid, not only as solvent but also as promoter. Ionic liquid was recycled and subsequently reused without any loss of the product. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500281267

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Room‐Temperature Ionic Liquid–Promoted
Williamson's Synthesis of Ethers: A Facile
Synthesis of Diaryloxymethanes
S. V. More a , S. S. Ardhapure a , N. H. Naik a , S. R. Bhusare a , W. N. Jadhav
a & R. P. Pawar a
a Organic Chemistry Synthesis Laboratory, Dnyanopasak College, Parbhani,
India
Published online: 20 Aug 2006.
To cite this article: S. V. More , S. S. Ardhapure , N. H. Naik , S. R. Bhusare , W. N. Jadhav & R. P. Pawar
(2005) Room‐Temperature Ionic Liquid–Promoted Williamson's Synthesis of Ethers: A Facile Synthesis of
Diaryloxymethanes, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:24, 3113-3118
To link to this article: http://dx.doi.org/10.1080/00397910500281267
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Synthetic Communicationsw, 35: 3113–3118, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500281267
Room-Temperature Ionic
Liquid–Promoted Williamson’s
Synthesis of Ethers: A Facile
Synthesis of Diaryloxymethanes
S. V. More, S. S. Ardhapure, N. H. Naik, S. R. Bhusare,
W. N. Jadhav, and R. P. Pawar
Organic Chemistry Synthesis Laboratory, Dnyanopasak College,
Parbhani, India
Abstract: A simple and efficient method has been developed for the synthesis of
phenolic ethers using room-temperature ionic liquid, not only as solvent but also as
promoter. Ionic liquid was recycled and subsequently reused without any loss of the
product.
Keywords: Williamson’s synthesis, ionic liquid, phenoxide ion
The development of environmentally friendly catalysts and solvents for
organic chemistry is an area of considerable importance. In the past few
years ionic liquids, especially those based on 1,3-dialkylimidazolium
cations, have been recognized as a possible environmentally benign alterna-
tive to volatile chemical solvents. Preparation of ethers is an important
synthetic reaction for which a wide variety of procedures has been
developed during the past decades. The Williamson reaction, discovered in
1850, is still the best general method for the preparation of asymmetrical as
well as symmetrical ethers.[1] Diaryloxymethanes are synthetically
important compounds used as fungicides,[2] parasiticides,[3] in the treatment
of liverfluke infection in mammals,[4] and in the preparation of condensation
Received in India April 7, 2005
Address correspondence to R. P. Pawar, Organic Chemistry Synthesis Laboratory,
Dnyanopasak College, Parbhani 431 401, India. E-mail: rppawar@yahoo.com,
bhusare71@yahoo.com
3113

3114
S. V. More et al.
polymers.[5] Diaryloxymethanes are used in the preparation of various
catalysts such as cavitionds[6] and crown ethers[7] and in the preparation of
diols[8] such as 2,20-dihydroxy-6,60-dimethoxy-1,10-biphenyl.
Diaryloxymethanes were prepared by methylation of appropriate phenol
with diiodomethane,[9] bromochloromethane,[10] and dichloromethane[7]
using different inorganic bases, such as CS2CO3,[6] KOH,[7] and NaH.[10]
The reaction of alkali metal phenolate with methylating agents was
generally carried out in several polar solvents such as DMSO, DMF, and
NMP[10] to facilitate the conversion. The sealed tube was required because
of the volatility of the methylating agents.[6] Various catalysts were used
such as dibenzo 18-crown-6-ether.[11] Biphasic phase-transfer catalysis
conditions using quaternary ammonium salts[12] have been reported, but the
reaction required longer time. Some other catalysts[7,11] and polymer
supporting reagents[13] have been also reported.
An ionic liquid[14,15] was used for regioselective o-alkylation of
naphthols, but C-alkylation also occurs and this method requires prolonged
time periods and harsh reaction conditions. In fact, all these reported
methods suffered from several drawbacks such as prolonged reaction
periods, low yields, harsh reaction conditions, critical isolation procedures,
and occurrence of side products.
Recently room-temperature ionic liquids as “green solvents” in organic
synthesis[16] have gained considerable importance because of their solvating
ability, negligible vapor pressure, and easy recyclability and reusability.[17]
These unique properties of ionic liquids make then a strong alternative to con-
ventional solvents. Herein we used the ionic liquid [bmim] Br for the reaction
of phenoxides with alkyldihalides. The ionic liquid [bmim] Br was prepared as
per the literature method.[17]
Substituted phenoxide ions react with dichloromethane in the presence
of ionic liquid 1-methyl-3-butyl imidazolium bromide [bmim] Br at 608C
without any added catalyst (Scheme 1). The synthesized diaryloxymethanes
were fully characterized by IR, 1H NMR, and 13C NMR, and physical
constants are assigned with their reported values in the literature. The ionic
liquid was recovered (almost 100%) and reused at least three times for
the reaction of p-methoxy phenoxide with dichloromethane without any
considerable loss in yield (Table 1).
We selected the use of dichloromethane and other reagents because of their
low cost, environmental friendliness, reusability, and recyclability. Ionic liquid
Scheme 1.

Diaryloxymethane Synthesis
Table 1. Yield data of product 8 after
the reuse of ionic liquid
3115
Run
Yield (%)
1
2
3
4
90
89
88
88
was chosen over DMSO, DMF, and NMP because of its solvating ability and
negligible vapor pressure. In some cases NMP was used where O-nitrophen-
oxide does not give any product, but when we used ionic liquid we got an
excellent isolated yield, which shows the importance of ionic liquid.
The reaction time was strongly dependent on the position of constituents
on the phenoxide ring. An electron-donating group on the phenoxide ring
enhances the nucleophilicity of the phenoxide and therefore shortens the
reaction time. The effect was more pronounced when the group is at the
para position. Conversely, an electron-withdrawing group has a strong deac-
tivating effect that requires longer reaction times.
In conclusion, room-temperature ionic liquids are found to be best
alternative to conventional solvents not only as a medium but also as a
promoter. Short reaction periods, mild reaction conditions, excellent
isolated yields, a variety of substrates, simple isolation procedures, and reusa-
bility of ionic liquid made this methodology valuable for synthetic organic
chemist as well as industry.
PREPARATION OF PHENOXIDE
Phenol and substituted phenols (1 mmol) were dissolved in aqueous sodium
hydroxide solution (1.2 mmol) and stirred for 2 h at room-temperature.
Water was evaporated under reduced pressure to get solid phenoxides.
PREPARATION OF DIARYLOXYMETHANES
A mixture of phenoxides (2 mmol) and dichloromethane (1 mmol) was stirred
in ionic liquid [bmim] Br (5 mL) at 608C for an appropriate time period as
shown in Table 2. Completion of the reaction was monitored by thin-layer
chromatography using 5% ethyl acetate in petroleum ether. The reaction
mixture was diluted with water (20 mL) and then extracted with ethyl
acetate (3 ꢀ 10 mL). The separated organic layer was dried over anhydrous
sodium sulfate, and the solvent was evaporated under reduced pressure to
afford the diaryloxymethanes. The product was purified by column

3116
S. V. More et al.
Table 2. Synthesis of diaryloxymethanes using ionic liquid [bmim] Br
a,b
Starting
material
Reaction
time (h)
Yield
(%)
Mp
(8C)
Entry
1
5
2
3
1
90
89
87
89
Colorless oil
31[12]
2
3
4
45[12]
41[12]
5
6
4
90
90
89[12]
2.5
70[12]
7
8
1
85
90
Colorless oil
56[12]
0.2
9
8
6
80
85
130[12]
10
146[12]
11
2
80
109–110
(continued)

Diaryloxymethane Synthesis
3117
Table 2. Continued
a,b
Starting
material
Reaction
time (h)
Yield
(%)
Mp
(8C)
Entry
12
3
80
Brown oil
13
6
78
161
aYields are of pure isolated products.
bProducts were characterized by IR, 1H NMR, and 13C NMR spectra and compared
with authentic samples.
chromatography using 5% ethyl acetate in petroleum ether as an eluent. The
ionic liquid was extracted from the aqueous layer with dichloromethane
(3 ꢀ 10 mL) and dried over anhydrous sodium sulfate, and the solvent was
evaporated under reduced pressure leaving behind the ionic liquid [bmim]
Br, which could be recycled.
ACKNOWLEDGMENT
The authors are thankful to Dr. Y. B. Vibhute, Department of Chemistry,
Yeshwant Mahavidyalaya, Nanded–431601, Maharashtra, India for his
valuable guidance.
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