A novel 3-nitrobenzeneboronic acid as an extremely mild and environmentally benign catalyst for the acetylation of alcohols under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2006.07.046

A novel 3-nitrobenzeneboronic acid is found to catalyse efficiently the acetylation of a wide range of alcohols as well as phenols with acetic anhydride in good to excellent yields at room temperature under solvent-free conditions. The reactions are clean and the catalyst is mild such that highly sensitive functional groups including oximes are stable to the reaction conditions.

Full text of DOI:10.1016/j.tetlet.2006.07.046

Tetrahedron Letters 47 (2006) 7263–7265
A novel 3-nitrobenzeneboronic acid as an extremely mild
and environmentally benign catalyst for the acetylation of
alcohols under solvent-free conditions
*
R. H. Tale and R. N. Adude
School of Chemical Sciences, S.R.T.M. University, Nanded 431606, Maharashtra, India
Received 20 March 2006; revised 27 June 2006; accepted 10 July 2006
Available online 17 August 2006
Abstract—A novel 3-nitrobenzeneboronic acid is found to catalyse efficiently the acetylation of a wide range of alcohols as well as
phenols with acetic anhydride in good to excellent yields at room temperature under solvent-free conditions. The reactions are clean
and the catalyst is mild such that highly sensitive functional groups including oximes are stable to the reaction conditions.
ꢀ
2006 Elsevier Ltd. All rights reserved.
8
With increasing environmental concerns and the regula-
tory constraints faced in the chemical and pharmaceuti-
cal industries, the development of environmentally
benign organic reactions has become a crucial and
duced including simple metal salts such as COCl ,
2
9
10
11
12
ZnCl2, TiCl –AgClO ,
Me SiCl,
LiClO4
and
4
4
3
1
3
14
MgClO4 as well as metal triflates such as Sc(OTf) ,
3
1
5
16
17
18
Me SiOTf, In(OTf)3, Cu(OTf)3 and Bi(OTf)3.
3
1
demanding area in modern organic chemical research.
Recently, perchlorates were reported to catalyse the
acetylation of alcohols, however, perchlorates, parti-
cularly of lithium, are reported to be explosive and
moisture sensitive. Very recently, molecular iodine
According to Wender, the ‘ideal synthesis’ is one in
which the target components are readily obtained in
one step and in quantitative yields from readily available
starting materials in an environmentally acceptable pro-
1
9
catalysed acetylation of alcohols was reported.
2
cess. Acetylation of alcohols is an important and com-
3
mon transformation in organic synthesis. In general,
Although a large number of methods for acetylation are
available, the practical applicability of most of these
methods suffers from limitations such as the use of, (1)
expensive, moisture sensitive and toxic catalysts, (2) long
reaction times and (3) a lack of generality. In view of the
acetyl chloride or acetic anhydride, in the presence
of a tertiary amine such as triethylamine or pyridine,
4
is used for the acetylation of alcohols. For practical
reasons, the latter is usually preferred. The use of 4-
dimethylamino)pyridine (DMAP)5 as a co-catalyst
modern demands of organic synthesis, there is still the
1
(
accelerates the acetylation process. However, to over-
come the problems associated with these basic catalysts,
need to develop an efficient, mild and environmentally
benign protocol for the acetylation of alcohols.
the use of Bu P for acetylation of base sensitive alcohols
3
6
was reported by Vedjes et al. In addition, protic and
In recent years, we have been engaged in evaluating the
catalytic potential of arylboronic acids, particularly
those with electron withdrawing substituents, in organic
Lewis acids, and on some occasions, solid acids have
also been reported to be effective for catalysing the acet-
ylation of alcohols.
7
20
synthesis. We reported that 3-nitrobenzeneboronic
acid 1 efficiently catalysed the selective transesterifica-
2
1
In view of the synthetic importance of this reaction, a
plethora of catalysts for acetylation have been intro-
tion of b-ketoesters under mild conditions. We rea-
soned that, catalyst 1, might also activate anhydrides
for acetylation of alcohols. Herein, we report that vari-
ous alcohols can be acetylated with acetic anhydride effi-
ciently, in good to excellent yields, in the presence of 1
(2.5 mol %) at room temperature under solvent-free
conditions (Scheme 1).
Keywords: 3-Nitrobenzeneboronic acid; Solvent-free reaction; Acety-
lation; Deoximation.
*
Corresponding author. Fax: +91 2462 29245; e-mail: rkht2002@
yahoo.com
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.046

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R. H. Tale, R. N. Adude / Tetrahedron Letters 47 (2006) 7263–7265
In order to establish the best reaction conditions, we
B(OH)2
performed an optimisation study using n-decanol as
the model substrate in the presence of varying amounts
of catalyst 1, might also activate anhydrides for acetyl-
ation of alcohols. As shown in Table 1, 2.5 mol % of
catalyst was found to be effective for acetylation of
n-decanol in 95% yield within 7 h. A threefold excess
of acetic anhydride was effective for the reaction to pro-
ceed at a reasonable rate. To explore the generality and
scope of the method, other alcohols and phenols were
acetylated with acetic anhydride using our optimised
reaction conditions. The results are collected in Table
O N
1
(2.5mol%)
2
R-OH
R-OAc
Ac O (3-10 equiv.), R.T.
2
Scheme 1.
Table 1. Acetylation of n-decanol with acetic anhydride catalysed by
a
1
b
Entry
Catalyst (mol %)
Time (h)
Yield (%)
1
2
3
4
5
1.0
1.5
2.0
2.5
2.5
10
10
10
10
7
42
56
78
90
2
. Structurally diverse alcohols such as primary, second-
ary, allylic and propargylic alcohols underwent smooth
acetylation in good to excellent yields and, in some
cases, in quantitative yields. Notably, hindered tertiary
alcohols such as 1-methylcyclohexanol and adamanta-
nol (entries 5 and 6) were acetylated cleanly and
efficiently under the present reaction conditions in high
c
95
a
b
c
1
All the products gave satisfactory spectral data (IR, H NMR).
Isolated yield.
.2 equiv of MgSO was added.
4
0
a
Table 2. Acetylation of alcohols and phenols catalysed by 3-nitrobenzeneboronic acid 1
b
Entry
Substrate
n-C10 21OH
n-C 17OH
Benzyl alcohol
4-Nitrobenzyl alcohol
Product
n-C10 21OAc
n-C 17OAc
Benzyl acetate
4-Nitrobenzyl acetate
Time (h)
Yield (%)
1
2
3
4
H
H
H
8
H
7
6
10
12
95
90
90
94
8
5
6
14
16
86
89
OH
OH
OAc
OAc
OH
OAc
7
14
97
Me
Me
8
9
11
14
12
95
91
Ph
OH
Ph
OAc
OH
CHOH
OAc
c
1
0
1
Ph
2
Ph
2
CHOAc
2
>99
O
O
Ph
Ph
c
1
17
>99
Ph
Ph
OH
OAc
d
1
1
2
3
Cholesterol
Cholesterol acetate
15
10
>99
OH
OAc
O
92
90
O
1
4
5
O N
OH
O N
OAc
8
2
2
HON
HON
d
1
12
95
OH
OAc
a
b
c
All the reactions were performed using 3 equiv of acetic anhydride unless otherwise stated.
Isolated yields.
To solubilise solid alcohol, 5 equiv of acetic anhydride was added.
The reactions were performed using 10 equiv of acetic anhydride.
d

R. H. Tale, R. N. Adude / Tetrahedron Letters 47 (2006) 7263–7265
7265
Table 3. Selective acetylation of 4-hydroxyacetophenone oxime using
various catalysts
in Table 2. After completion, the reaction was quenched
a
3
with water (20 cm ). The mixture was extracted with
3
b
Entry
1
Catalyst
Time (h)
12
Selectivity (%)
ethyl acetate (2 · 30 cm ) and the combined organic
3
layer was washed with saturated NaHCO (2 · 20 cm )
3
B(OH)2
95
3
and brine (20 cm ). Evaporation of the solvent followed
by purification by column chromatography (silica
gel, eluent, ethyl acetate–hexane 1:9) gave the pure
acetate.
NO2
c
3
2
3
In(OTf)
LiClO
0.1
22
0
82
4
a
All reactions were performed using 5 equiv of acetic anhydride in the
presence of 2.5 mol % of the catalyst at room temperature.
Isolated yield of 4-acetyloxyacetophenone oxime.
Acknowledgement
b
c
The authors are grateful to the University Grants Com-
mission (UGC), India, for financial support.
4-Acetyloxyacetophenone was obtained as the only product within
5
min.
yields. Moreover, acid sensitive alcohols such as furfuryl
alcohol (entry 13) were acetylated in excellent yields
without giving any side products. The reaction can also
be applied to the acetylation of phenols. The extremely
mild behaviour of catalyst 1 was evident from the fact
that the acetylation of 4-hydroxyacetophenone oxime
References and notes
1
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Benign Chemical Synthesis and Procedures; Oxford Science
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VCH: New York, 1989, p 980.
(
(
entry 15) was achieved in high yield with no deprotec-
3
tion observed at all.
To expand the scope of the present reaction further, we
performed a comparative study in which the selective
acetylation of 4-hydroxyacetophenone oxime using our
4
5
. Steglich, W.; Hofle, G. Angew. Chem., Int. Ed. Engl. 1969,
8, 981.
catalyst was compared with In(OTf) and LiClO under
3
4
solvent-free conditions. The results are collected in
Table 3. Indium triflate catalysed the acetylation (Table
6. Vedjes, E.; Bennett, N. S.; Conn, L. M.; Diver, S. T.;
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Chem. 1993, 58, 7286.
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7
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. (a) Backer, R. H.; Bordwell, F. G. Org. Synth. 1955, 3,
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phenone as the only product. However, acetylation
1
41; (b) Miyashita, M.; Shiina, I.; Miyoshi, S.; Mukaiy-
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using LiClO (Table 3, entry 3) gave comparable selec-
4
9
tivity, however, the reaction took longer to reach com-
pletion. Although the rate of acetylation with 1 is less
than those catalysed by expensive metal triflates, it is
faster than those involving catalysts (10–20 mol %) such
1
1
0. Nakae, Y.; Kusaki, I.; Sato, T. Synlett 2001, 1584.
1. Bartoli, G.; Bosco, M.; Dalpozzo, R.; Marcantoni, E.;
Massaccesi, M.; Rinaldi, S.; Sambri, L. Synlett 2003, 39.
as LiClO , and NBS, and gives comparable yields of
12. Ono, F.; Negoro, R.; Sato, T. Synlett 2001.
13. Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J.
Org. Chem. 1996, 61, 4560.
4
products despite using only 2.5 mol % of the catalyst.
Unfortunately, all attempts to acetylate diols by this
method proved fruitless. The probable reason for this
failure is that the catalyst might be trapped by the diol
as boronic acids react readily with diols to form 1,3,2-
dioxaborolanes.
1
1
1
1
4. Procopiou, P. A.; Baugh, S. P. D.; Flack, S. S.; Inglis, G.
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1
999, 1743.
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C.; Kakuda, A.; Otera, J. J. Org. Chem. 2001, 66, 8926.
Arylboronic acids are usually crystalline solids, stable to
air and moisture. Such evidence as exists, indicates that
they are of relatively low toxicity [benzeneboronic acid,
LD , oral rat = 740 mg/kg] and have low environmen-
18. (a) Schumacher, J. C. Perchlorates—Their Properties,
Manufacture and Use. In ACS Monograph Series; Rein-
hold: New York, 1996; (b) Long, J. Chem. Health Saf.
5
0
tal impact. Moreover, a small amount of boronic acid 1
2.5 mol %) is effective as a catalyst for the acetylation of
(
2
002, 9, 12.
alcohols and phenols.
1
2
9. Phukan, P. Tetrahedron Lett. 2004, 45, 4785.
0. (a) Tale, R. H.; Patil, K. M. Tetrahedron Lett. 2002, 43,
General procedure for the acetylation of alcohols and phe-
nols:
A mixture of the alcohol or phenol (2 mmol), acetic
anhydride (3–10 mmol) and catalyst 1 (0.025 mmol)
was stirred at room temperature for the time indicated
9
715; (b) Tale, R. H.; Patil, K. M.; Dapurkar, S. E.
Tetrahedron Lett. 2003, 44, 3427; (c) Sagar, A. D.; Tale, R.
H.; Adude, R. N. Tetrahedron Lett. 2003, 44, 7140.
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Synlett 2006, 417.