Task-oriented use of ionic liquids: Efficient acetylation of alcohols and phenols

Article abstract of DOI:10.1016/j.tetlet.2011.04.079

The ionic liquid 1-butyl-3-methylimidazolium acetate proves to be an excellent reaction medium for the acetylation of alcohols and phenols, providing better conditions than the acidic 1-butyl-3-methylimidazolium bisulfate. Reactions were carried at room temperature, with only a 10% excess of acylating agent and with no other solvent or catalyst added.

Full text of DOI:10.1016/j.tetlet.2011.04.079

Tetrahedron Letters 52 (2011) 3339–3341
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Task-oriented use of ionic liquids: efficient acetylation of alcohols and phenols
a,
⇑
b
b
c
c
Ignacio López , José Luis Bravo , Manuel Caraballo , José Luis Barneto , Guadalupe Silvero
a
Departamento de Química Orgánica e Inorgánica, Escuela Politécnica, Universidad de Extremadura, Cáceres 10003, Spain
Departamento de Química Orgánica e Inorgánica, Facultad de Ciencias, Universidad de Extremadura, Badajoz 06006, Spain
Departamento de Química Orgánica e Inorgánica, Facultad de Veterinaria, Universidad de Extremadura, Cáceres 10003, Spain
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
The ionic liquid 1-butyl-3-methylimidazolium acetate proves to be an excellent reaction medium for the
acetylation of alcohols and phenols, providing better conditions than the acidic 1-butyl-3-methylimida-
zolium bisulfate. Reactions were carried at room temperature, with only a 10% excess of acylating agent
and with no other solvent or catalyst added.
Received 2 February 2011
Revised 13 April 2011
Accepted 19 April 2011
Available online 27 April 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Acetylation
Alcohols
Phenols
Ionic liquids
The acetylation reaction of hydroxyl groups in alcohols and
phenols constitutes an important synthetic procedure that is
widely employed for protection in multi-step synthesis due to its
easy reversibility. Protection reactions have to proceed rapidly,
readily, quantitatively and keeping costs to a minimum. Typically,
the acetylation of hydroxyl groups is performed with an excess of
acetic anhydride under basic or acidic catalysis; in some cases
In order to take advantage of beneficial ionic liquid features,
such as nonvolatility, ‘greenness’ and wide solvent ability, a pur-
2
0
pose-oriented selection of the melt is essential. For instance,
the widely used 1-butyl-3-methylimidazolium hexafluorophos-
phate or 1-butyl-3-methylimidazolium tetrafluoroborate em-
ployed as solvents for the acetylation of glucose yielded no
1
0
product. On the other hand, benzoate imidazoliums showed cat-
alytic activity in this reaction, yet the acetate product formed com-
1,2
acetyl halides have been used. In the light of the 12 principles
3
10
of Green Chemistry, protection/deprotection reactions are intrin-
plicated the recovery of products. Depending on cation/anion
sically not-green, and better avoided whenever possible.
combinations, the physico–chemical properties of ILs can be tuned
for a particular application, in search of novel functional com-
pounds termed as Task-Specific Ionic Liquids (TSILs).21
Ionic liquids, in particular, have received remarkable attention
in the last decade or so as reaction media and/or catalysts in organ-
ic synthesis. They have also been employed in the acylation of hy-
droxyl groups. Thus, Brönsted acidic 1-H-3-methylimidazolium
bisulfate has been used as the catalyst in the acetylation of alcohols
In our group, we have been testing the use of ionic liquids as reac-
tion media in organic reactions. Thus, new methodologies involving
2
2
23
ionic liquids and Lewis acid catalysts, ultrasounds, and mineral
4
24
and phenols; as well as trimethylammoniumbutanesulfonate
catalysts and microwaves have been studied. In further pursuing
2
5,6
bisulfate, and Lewis acidic ionic liquids have been used as well.
these investigations, we have now studied the use of two simple io-
nic liquids, the acidic 1-butyl-3-methylimidazolium bisulfate
[bmim][HSO ], and the mildly basic 1-butyl-3-methylimidazolium
4
In other cases, the ionic liquid is used as the immobiliser for Lewis
acidic rare-earth based catalysts.7 Basic catalytic activity by an io-
nic liquid has been reported in the acetylation of alcohols and car-
,8
acetate, [bmim][OAc]. This choice is based on their distinctive Brön-
sted acid–base characteristics. Accordingly, the former could act as
an acid catalyst, while the latter might show basic catalysis. Further-
more, these two ionic liquids are easy to synthesise and commer-
cially available at a lower cost than analogous melts such as
dicyanamides, which have proven to be excellent reaction media
9
,10
bohydrates.
The use of enzymes and ionic liquids in the
11
acylation of levoglucosan, and glucosides has also been re-
1
2
ported. One imidazolium bromide ionic liquid has been em-
ployed as the medium for the ultrasonic activation of alcohols
with acetic anhydride.13 Moreover, acylimidazolium derivatives
1
4–19
9
have been used as acylating agents in protection of alcohols.
for acetylation of hydroxyl groups. The acetate melt encompasses
some other desirable features, the nontoxic nature of its anion,
and the fact that it is a common ion involved in these processes.
⇑
Corresponding author.
E-mail address: iglomar@unex.es (I. López).
We report herein that both [bmim][HSO
efficient reaction media for a wide variety of alcohols, including
4
], and [bmim][OAc] are
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.04.079

3
340
I. López et al. / Tetrahedron Letters 52 (2011) 3339–3341
Table 1
Acetylation reactions in ionic liquids
Entry
Substrate
Product
Solvent
[
bmim][HSO
4
]
[bmim][OAc]
Timea
Yieldb
Timea
Yieldb
1c
2c
3c
OH
OAc
OAc
10
20
20
90
85
88
5
5
5
94
90
91
OH
OH
OH
OAc
OAc
4c
5d
6c
60f
40
90
—g
5
5
5
95
92
89
HO
AcO
25
OH
OH
OAc
OAc
OAc
60f
OH
7c
8c
10
10
89
83
<1
5
91
92
OH
OAc
OH
OAc
9e
O
O
No reaction
—
15
90
HO
HO
AcO
AcO
OH
OAc
OH
OAc
a
b
c
d
e
f
Time (min) for 100% conversion by tlc monitoring.
Isolated yield.
1
2
5
1 mmol of Ac
2 mmol of Ac
5 mmol of Ac
2
O added.
2
O added.
2
O added.
Reaction not completed.
Not isolated.
g
phenols and glucose, showing not only good solvent ability, but
also catalytic activity and reusability. All products were identified
by H NMR.
Table 2
Recycle experiments. Acetylation of b-naphthol
1
Run
Solvent
In a typical experiment, 10 mmol of the alcohol was dissolved,
under stirring, in 10 mmol (ca. 2 mL) of the corresponding ionic
liquid at room temperature. Then 1.10 equiv of acetic anhydride
per hydroxyl group was added to the medium and the reaction
was monitored by tlc. Products were isolated either by extraction
with ether and/or petroleum ether, washed with aqueous bicar-
bonate or by distillation under reduced pressure. Table 1 summa-
rises results obtained for both ionic liquids and a variety of
alcohols.
[
bmim][HSO
4
]
[bmim][OAc]
Timea Yieldb
Timea
Yieldb
1
2
3
4
5
20
20
20
20
20
85
77
73
85
80
10
10
10
10
10
95
88
91
87
76
a
At this unoptimised time 100% conversion, by tlc monitoring, was achieved in
all cases.
b
In [bmim][HSO
4
] all hydroxyl groups were transformed into
-glucopyra-
Isolated yield.
their corresponding acetyl esters, except those for b-
D
nose. It is important to note that while all other substrates are sol-
uble in the ionic liquid or the solvent system formed by the ionic
liquid and acetic anhydride, glucose is not, this, probably being
the reason for its nonreactivity. Primary, benzylic and aromatic
alcohols reacted quantitatively in short reaction times at room
temperature, yielding the acetylated derivatives in solution.
Remarkably, only a slight excess of acetic anhydride per hydroxyl
group (1.1 mol/1.0 mol), in an equimolar amount of ionic liquid
is needed.
calculation. The procedure was the same as before. Results gath-
ered in Table 2 show the feasibility of re-using these ionic liquids
for five cycles with only a slight loss of activity.
Summing up, a rapid, clean, and efficient method for the acety-
lation of hydroxyl groups at room temperature with only a 10% ex-
cess of acetylating agent is reported. Quantitative transformation is
achieved in very short reaction time. The ionic liquids perform a
catalytic activity, as well as acting as the solvent. The results ob-
tained show that the acetate ionic liquid outperforms the acidic
bisulfate one. It is important to note that the acetate anion is safer
and cheaper and, furthermore, due to its common nature with the
by-product, acetic acid, spares all the work-up hassle arising from
the presence of another species in the reaction medium. Products
can be isolated by simple extraction, or distillation when suitable,
and the reaction medium can be re-used at least for five times with
nearly no loss of activity.
Moreover, all the reactions carried out in [bmim][OAc] pro-
ceeded better than in [bmim][HSO ], under the same conditions.
4
Per-O-acetylation of glucose, and acetylation of secondary, and
allylic alcohols were successful in 5–15 min. It is worth mentioning
the higher solubility of the glucose, compared to the other ionic li-
quid. Again, all the products were soluble in the reaction medium.
These results show that there must be a significant catalytic effect
of the acetate anion. Moreover, this anion and the acetic acid
formed buffer the solution, keeping a stable pH.
It is important to check whether these reaction media can be re-
used. For that reason, several experiments were run after extrac-
tion of the products. b-Naphthol was used as a model substrate
because the solid product formed can be readily weighed for yield
In conclusion, this protocol constitutes an improved, efficient
methodology compared to others based on acid/base catalysis
and/or ionic liquids. To extend its scope and limitations, and to
gain insight into mechanistic details involved, further experimen-
tal and theoretical studies are under way.

I. López et al. / Tetrahedron Letters 52 (2011) 3339–3341
3341
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