Microwave-promoted, one-pot conversion of alkoxymethylated protected alcohols into their corresponding nitriles, bromides, and iodides using [bmim][InCl4] as a green catalyst

Article abstract of DOI:10.1016/j.tetlet.2010.04.056

The Lewis acid room temperature ionic liquid, [bmim][InCl₄], was found to be an efficient and green catalyst for the highly chemoselective and one-pot conversion of MOM- or EOM-ethers into their corresponding nitriles, bromides, and iodides under microwave irradiation. The procedures are simple, rapid, and high yielding. The catalyst exhibited a remarkable reactivity and is reusable.

Full text of DOI:10.1016/j.tetlet.2010.04.056

Tetrahedron Letters 51 (2010) 3274–3276
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Tetrahedron Letters
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Microwave-promoted, one-pot conversion of alkoxymethylated protected
alcohols into their corresponding nitriles, bromides, and iodides using
[
bmim][InCl ] as a green catalyst
4
*
*
Arsalan Mirjafari, Iraj Mohammadpoor-Baltork , Majid Moghadam , Shahram Tangestaninejad,
Valiollah Mirkhani, Ahmad Reza Khosropour
Catalysis Division, Department of Chemistry, Faculty of Science, University of Isfahan, Isfahan 81746-7344, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The Lewis acid room temperature ionic liquid, [bmim][InCl ], was found to be an efficient and green cat-
4
Received 16 December 2009
Revised 23 March 2010
Accepted 12 April 2010
Available online 18 April 2010
alyst for the highly chemoselective and one-pot conversion of MOM- or EOM-ethers into their corre-
sponding nitriles, bromides, and iodides under microwave irradiation. The procedures are simple,
rapid, and high yielding. The catalyst exhibited a remarkable reactivity and is reusable.
Ó 2010 Elsevier Ltd. All rights reserved.
One-pot transformations represent a strategy combining eco-
nomic and environmental aspects. Also, one-pot conversions of
functional groups play a critical role in the successful synthesis
of multi-functional complex molecules. These processes typically
consist of two or more steps, which are performed without isola-
tion of any intermediates, thus leading to savings in energy and
raw materials and also reducing time.1 Due to the importance of
these transformations, significant efforts have been, and still are
being devoted to find and develop new types of these reactions.
Methoxymethyl ethers (MOM-ethers) or ethoxymethyl ethers
and specific applications in academic and industrial fields.8,9 There
has been a substantial growth in the use of RTILs as environmen-
8
tally benign and useful media in diverse applications such as
1
0
11
12
catalysis, biocatalysis, separation technology, biomass disso-
1
3
14
lution, energetic materials, and active pharmaceutical ingredi-
ents (APIs). Due to their ionic nature, ionic liquids are ideal for
use in microwave-promoted synthesis on account of their negligi-
1
5
1
6
ble vapor pressure and high thermal stability.
[
bmim][InCl4]
(
EOM-ethers) are important intermediates and are used to protect
R-OCH OR' + [Bu N][X]
R-X
2
4
alcohols due to their easy access and high stability under both ba-
sic and moderately acidic conditions.2 On the other hand, nitriles
are important synthetic transformation precursors, especially of
esters, amides, carboxylic acids, amines, and nitrogen-containing
MW
R= ArCH , alkyl, allyl
X= CN, Br, I
2
R'= CH , CH CH
3
2
3
3
heterocycles. They have been used as synthetic intermediates
Scheme 1.
for agricultural and pharmaceutical chemicals.4 Furthermore,
organic halides, especially bromides and iodides, are indispensable
in organic synthesis, and their transformations into useful com-
Table 1
5
pounds are widely documented in the literature. They serve as
Direct conversion of benzylmethoxymethyl ether into its corresponding nitrile in the
a
intermediates in a wide variety of reactions,6 and also in carbon–
presence of various catalysts
7
carbon bond formation via radical or substitution reactions.
Therefore, direct transformation of methoxymethyl- and ethoxy-
methyl-protected alcohols into nitrile, bromide, and iodide func-
tional groups can be considered important in organic synthesis.
There has been major research effort in the area of ionic liquids
over the last two decades. The development and use of room
temperature ionic liquids (RTILs) have emerged as a fascinating
technology because of their unique physicochemical properties
Entry
Catalyst
InCl
[bmim][AlCl
[bmim][FeCl
Yieldb (%)
1
2
3
4
5
3
56
22
31
88
0
4
]
4
]
[bmim][InCl
No catalyst
4
]
a
*
Corresponding authors. Tel.: +98 311 7932705; fax: +98 311 6689732.
4
Reaction conditions: benzylmethoxymethyl ether (1 mmol), (n-Bu N)CN(2 m-
E-mail addresses: imbaltork@sci.ui.ac.ir (I. Mohammadpoor-Baltork), mogha
damm@sci.ui.ac.ir (M. Moghadam).
mol), catalyst (0.28 mmol).
b
Isolated yield.
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.04.056

A. Mirjafari et al. / Tetrahedron Letters 51 (2010) 3274–3276
3275
Recently, several methods have been reported for the conver-
sion of alcohols and their derivatives into their corresponding ha-
EOM-ethers into their corresponding bromides, iodides, and ni-
triles in high yields under microwave irradiation conditions
(Scheme 1).
1
7–21
lides and nitriles.
However, to the best of our knowledge,
the transformation of MOM- and EOM-ethers into their nitriles,
bromides, and iodides has not been described in the literature.
Herein, we report the use of 1-butyl-3-methylimidazolium tetra-
chloroindate [bmim][InCl ], as a novel, highly efficient and eco-
4
friendly catalyst for the one-pot conversion of various MOM- or
In these reactions no corrosive substances were used and no
waste formation was observed. The experimental procedure for
these reactions was remarkably simple and required no toxic or-
ganic solvent or inert atmosphere. We found that the transforma-
tions could be accomplished by exposing a mixture of the
Table 2
Conversion of MOM- and EOM-ethers into their corresponding nitriles, bromide, and iodides catalyzed by [bmim][InCl
4
] under MW irradiationa
Entry
R
EOM-ether
MOM-ether
Yield, % (time, min)b
Yield, % (time, min)b
X = CN
X = Br
X = I
X = CN
X = Br
X = I
1
2
3
4
5
6
7
8
9
C
6
H
5
CH
2
88 (4.5)
84 (4.5)
86 (4.5)
82 (5.5)
84 (4.5)
86 (4)
82 (5.5)
84 (4.5)
81 (5)
83 (4.5)
81 (4.5)
84 (4.5)
79 (5.5)
81 (4.5)
83 (4)
79 (5.5)
82 (4.5)
79 (5)
86 (4.5)
83 (4.5)
86 (4.5)
82 (5.5)
83 (4.5)
85 (4)
81 (5.5)
84 (4.5)
81 (5)
88 (4.5)
85 (4.5)
87 (4.5)
83 (5.5)
86 (4.5)
86 (4)
82 (5.5)
84 (4.5)
83 (5)
82 (4.5)
84 (4.5)
83 (4.5)
79 (5.5)
82 (4.5)
83 (4)
81 (5.5)
82 (4.5)
81 (5)
87 (4.5)
85 (4.5)
87 (4.5)
83 (5.5)
86 (4.5)
86 (4)
82 (5.5)
84 (4.5)
81 (5)
4-(CH
4-CH
2-HOC
3-CH
3-CH
4-CH
4-PhCH
2-ClC
4-ClC
2,4-Cl
2-BrC
4-BrC
3-O
4-O
C
C
3
)
3
CC
CH
CH
O, 4-HOC
6
H
4
CH
2
c
3
C
6
H
4
2
6
H
4
2
3
3
3
6
H
3
CH
2
OC
OC
6
H
H
4
4
6
CH
CH
H
2
6
2
2
OC
4
CH
2
6
H
4
CH
CH
2
10
11
12
13
14
15
16
17
18
19
6
H
4
2
83 (5)
81 (5)
82 (5)
84 (5)
81 (5)
83 (5)
2
C
6
H
3
CH
2
80 (5.5)
80 (5.5)
82 (5)
88 (3)
90 (2)
92 (2)
86 (4)
87 (4)
85 (4)
78 (5.5)
77 (5.5)
81 (5)
84 (3)
85 (2)
88 (2)
82 (4)
82 (4)
83 (4)
79 (5.5)
79 (5.5)
82 (5)
86 (3)
88 (2)
91 (2)
84 (4)
86 (4)
84 (4)
82 (5.5)
80 (5.5)
84 (5)
89 (3)
91 (2)
92 (2)
86 (4)
87 (4)
86 (4)
77 (5.5)
78 (5.5)
80 (5)
86 (3)
86 (2)
89 (2)
83 (4)
83 (4)
82 (4)
80 (5.5)
78 (5.5)
83 (5)
88 (3)
88 (2)
92 (2)
86 (4)
87 (4)
84 (4)
6
H
H
4
4
CH
CH
2
6
2
2
NC
NC
6
H
H
4
CH
CH
2
2
6
4
2
6
H
H
5
CH@CHCH
CH CH
2
6
5
2
2
CH
CH
3
(CH
2
)
)
5
CH
CH
2
3
(CH
2
6
2
a
b
c
Reaction conditions: alkoxymethyl ether (1 mmol), [n-Bu
Isolated yield.
4
N][X] (2 mmol), [bmim][InCl
4
] (0.28 mmol).
0
4
.56 mmol of catalyst and 4 mmol of [Bu N][X] were used.
Table 3
Competitive conversions of various MOM-ethers into nitriles, bromides, and iodides catalyzed by [bmim][InCl
] under MW irradiationa
X = Br
4
Entry
Ethers
Products
X = CN
Time (min)
X = I
Yieldb (%)
88
Yieldb (%)
Time (min)
Yieldb (%)
87
Time (min)
1
82
4.5
4.5
4.5
1
8
9
8
13
82
—
17
87
—
2
4.5
4.5
4.5
—
3
88
—
82
—
87
—
4.5
4.5
4.5
a
4 4
Reaction conditions: alkoxymethyl ether (1 mmol), [n-Bu N][X] (2 mmol), [bmim][InCl ] (0.28 mmol).
Isolated yield.
b

3
276
A. Mirjafari et al. / Tetrahedron Letters 51 (2010) 3274–3276
alkoxymethyl ether (1 mmol), [n-Bu
4
N][X] (X = CN, Br or I)
] (0.28 mmol) to MW irradiation
170 W, 135–140 °C) for 2.0–5.5 min. On the other hand, the
Supplementary data
(
(
2 mmol), and [bmim][InCl
4
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.04.056.
yields of these reactions did not exceed more than 22% under ther-
mal conditions (135 °C) even after long reactions times. The reac-
tion was not successful in the absence of catalyst or MW
irradiation.
References and notes
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8
9
.
.
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MOM-ethers (Table 3). The results indicated that this protocol
was potentially applicable for the chemoselective conversion of
primary alkoxymethyl ethers in the presence of secondary, tertiary,
and phenolic ethers. Furthermore, this method was appropriate for
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1
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In conclusion, a novel, efficient, eco-friendly, and chemoselec-
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