Microwave-assisted NiCl2 promoted acylation of alcohols

Article abstract of DOI:10.1081/SCC-200036636

A microwave oven acylation of alcohols by carboxylic acid anhydrides has been developed. NiCl₂ has been proven an efficient catalyst for the acylation of primary, secondary, and tertiary alcohols and phenols under microwave conditions.

Full text of DOI:10.1081/SCC-200036636

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Microwave‐Assisted NiCl2
Promoted Acylation of
Alcohols
a
Violetta Constantinou‐Kokotou & Anna
a
Peristeraki
a
Chemical Laboratories, Agricultural University of
Athens, Iera Odos, 75, Athens, 11855, Greece
Published online: 10 Jan 2011.
To cite this article: Violetta Constantinou‐Kokotou & Anna Peristeraki
2004): Microwave‐Assisted NiCl Promoted Acylation of Alcohols, Synthetic
(
2
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:22, 4227-4232
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 22, pp. 4227–4232, 2004
Microwave-Assisted NiCl Promoted
2
Acylation of Alcohols
*
Violetta Constantinou-Kokotou and Anna Peristeraki
Chemical Laboratories, Agricultural University of Athens,
Athens, Greece
ABSTRACT
A microwave oven acylation of alcohols by carboxylic acid anhydrides
has been developed. NiCl has been proven an efficient catalyst for the
2
acylation of primary, secondary, and tertiary alcohols and phenols
under microwave conditions.
Key Words: Acetylation; Acylation; Microwave; Metal catalysis.
Acylation of alcohols is one of the most frequently used transformations
in organic synthesis presenting both academic as well as industrial interest.
Acid anhydrides have been proven the most useful reagents for the reaction
*
Correspondence: Violetta Constantinou-Kokotou, Chemical Laboratories, Agri-
cultural University of Athens, Iera Odos, 75, Athens 11855, Greece; E-mail: vikon@aua.gr.
4
227
DOI: 10.1081/SCC-200036636
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4
228
Constantinou-Kokotou and Peristeraki
[1]
in the presence of base or acid catalysts. 4-(Dimethylamino)pyridine
(
the acylation of alcohols at enhanced rate.
DMAP) is the most popular among the nucleophilic catalysts catalyzing
[
2,3]
Besides the nucleophilic cata-
lysts, a number of acidic catalysts have been studied so far. A variety of
[
4]
[5]
Lewis acids such as ZnCl , CoCl2, and in particular metal triflates such
2
[7]
[6]
[8]
[8]
as Sc(OTf)3, Bi(OTf)2, Cu(OTf)2, and Sn(OTf)2 have been found to
be effective catalysts for acylation. During the past decade, the interest in
[9–11]
microwave-assisted organic synthesis has increased significantly.
recently, the microwave oven synthesis of esters promoted by imidazole has
Most
[
12]
been reported.
In the present article, we describe our studies on the micro-
wave assisted acylation of alcohols in the presence of NiCl as promoter.
2
A common microwave oven was used for the experiments and the
reaction mixture each time was irradiated at 600 W. The results obtained for
the acylation of benzyl alcohol under various conditions are presented in
Table 1. When a mixture of benzyl alcohol and acetic anhydride in the
absence of any catalyst was irradiated for 7 min in 1 : 2 and 1 : 1 molar ratio,
benzyl acetate was isolated in 66% and 50% yield, respectively. However,
.
in the presence of 5% NiCl2 6H O the yield of the reaction was 100% and
2
7
0%, when the molar ratio was 1 : 2 and 1 : 1, respectively. In the absence
of any catalyst and when the ratio of benzyl alcohol and acetic anhydride
was 1 : 2, the product was obtained quantitatively after 14 min under
.
irradiation. Similar results were obtained when CoCl2 6H O instead of
2
.
.
NiCl2 6H O. Because NiCl2 6H O is cheaper than CoCl2 6H O,
.
2
2
2
.
the acylation reaction was studied by using NiCl2 6H O as a catalyst.
Direct acetylation of benzyl alcohol by acetic acid under microwave
2
.
irradiation and in the presence of NiCl2 6H O led to low yields. Even
when the acetylating agent was used in excess (alcohol : acid 1 : 15), benzyl
2
Table 1. Acylation of benzyl alcohol under microwave irradiation.
Benzyl alcohol :
acylating agent ratio
Time
(min)
Yield
(%)
Acylating agent
Catalyst
(
(
(
(
(
(
(
CH CO) O
1 : 2
1 : 1
1 : 2
1 : 2
1 : 1
1 : 2
1 : 1
1 : 15
1 : 2
—
—
—
7
7
66
50
3
3
3
3
2
2
2
2
CH
CH
CH
CO)
CO)
CO)
O
O
O
14
7
98
.
NiCl
2
6H
NiCl2 6H O
2
O
100
70
.
CH CO) O
7
3
3
3
2
2
2
2
.
CH
CH
CO)
CO)
O
O
CoCl
CoCl
2
2
6H
6H
2
O
O
7
100
70
.
2
7
.
CH COOH
3
NiCl2 6H O
2
12
8
21
67
.
(
CH
3
CH
2
CO)
2
O
NiCl
2
6H
2
O

Microwave-Assisted NiCl Promoted Acylation of Alcohols
2
4229
acetate was isolated in 21% yield after 12 min in the microwave oven, under
reflux. Furthermore, benzyl propionate was isolated in high yield when a
mixture of benzyl alcohol and propionic anhydride (1 : 2) was irradiated in
.
the presence of NiCl2 6H O.
2
The above results indicate that NiCl is an efficient catalyst for the
2
microwave assisted acylation of benzyl alcohol. To explore the scope and
the limitations of the method, a variety of primary, secondary, and tertiary
alcohols and phenols were acetylated by acetic anhydride in a microwave
oven using NiCl as the catalyst. The results are summarized in Table 2.
2
Esters of primary alcohols such as p-methoxybenzyl alcohol (entry 1),
o-and p-nitrobenzyl alcohol (entry 2 and 3), 3-phenylpropanol (entry 4),
geraniol (entry 5), nerol (entry 6) were isolated in high to excellent
yields. Acetylation of citronellol (entry 7) was accomplished in a moderate
yield. Acetylated phenol was isolated in quantitative yield (entry 8),
whereas thymol (entry 9) and 3-hydroxybenzaldehyde (entry 10) were acetyl-
ated in 78% and 60% yield, respectively, after irradiation for 10 and 12 min.
When our protocol was applied to secondary alcohols such as cyclohexanol
(
entry 11) and borneol (entry 12), the desired acetates were obtained in 80% and
8%, respectively. Acetylation of 1,2-hexanediol (entry 13) using a 1 : 1 ratio
6
of acetic anhydride per hydroxyl group for 14 min led to a mixture 7 : 3 of
diacetylated : monoacetylated compound. Increasing the ratio to 1 : 1.5 per
hydroxyl group the diacetylated compound was isolated in 88% yield.
Tertiary alcohols (entries 15 and 16) were esterified in low yields (20 and
1
4%, respectively).
All the products are known compounds and are easily identified by
comparison of their physical properties with those of authentic samples.
In conclusion, our esterification method under microwave conditions in
the presence of NiCl2 can be readily applied to a variety of alcohols
(primary, secondary, and tertiary) and phenols. The microwave-assisted
acetylation has the benefit of reducing reaction times in comparison with
acetylation under conventional conditions. The advantages of the present
method in terms of fast reaction rates and ease of manipulation should
make this protocol a valuable alternative to the existing methods.
TYPICAL EXPERIMENTAL PROCEDURE
In a typical experiment the mixture of alcohol and acetic anhydride (1 : 2)
was irradiated in the microwave oven at 600 W for 7–12 min in the presence
.
of 5% NiCl2 6H O. The reaction mixture was extracted with ethyl acetate or
2
ether and the organic layer was washed with H O, 10% NaHCO and brine and
2
3
was dried over MgSO . The solvent was evaporated, and the residue was
4

4
230
Constantinou-Kokotou and Peristeraki
Table 2. Esterification of alcohols with acetic anhydride in the presence of NiCl
2
.
Time
(min)
Yield
(%)
Entry
1
Alcohol : Ac O
2
Alcohol
1 : 2
1 : 2
7
8
98
2
90
3
4
5
1 : 2
1 : 2
1 : 2
10
7
90
98
83
8
6
7
1 : 2
1 : 2
8
8
87
62
8
9
1 : 2
1 : 2
10
10
96
78
1
0
1 : 2
12
60
1
1
1
2
1 : 2
1 : 2
10
10
80
68
a
70 : 30
b
1
3
1 : 2
14
(
continued)

Microwave-Assisted NiCl Promoted Acylation of Alcohols
2
4231
Table 2. Continued.
Time
(min)
Yield
(%)
Entry
Alcohol : Ac
2
O
Alcohol
1
4
5
6
1 : 3
10
12
12
88
1
1 : 2
1 : 2
20
14
1
a
Diacetylated compound.
Acetylation of the primary hydroxy group only.
b
purified by column chromatography by using petroleum ether : ether 8 : 2 as
eluent.
ACKNOWLEDGMENT
The authors thank the Greek Ministry of Education and European
Community for financial support in the frame of fellowships for research
“
Heraklitos”.
REFERENCES
. Larock, R.C. Comprehensive Organic Transformations; VCH Publishers:
New York, 1989; 980–985.
1
2
. Hoefle, G.; Steglich, V.; Vorbruggen, H. Angew. Chem., Int. Ed. Engl.
1
. Scrieven, E.F.V. Chem. Soc. Rev. 1983, 12, 129.
. Baker, R.H.; Bordwell, F.G. Organic Syntheses; Wiley, New York,
978, 17, 569.
3
4
1955; Vol. 3, 141.
. Iqbal, J.; Srivastara, R.R. J. Org. Chem. 1992, 57, 2001.
5
6
. Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Org. Chem.
1
996, 61, 4560.
. Orita, A.; Tanahashi, C.; Kakuda, A.; Otera, J. J. Org. Chem. 2001,
6, 8926.
7
6

4
232
Constantinou-Kokotou and Peristeraki
8
9
. Chandra, K.L.; Saravanan, P.; Singh, R.K.; Singh, V.K. Tetrahedron
002, 58, 1369.
. Caddick, S. Tetrahedron 1995, 51, 10403.
2
10. Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199.
11. Lidstroem, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron 2001,
57, 9225.
2. Hirose, T.; Kopek, B.G.; Wang, Z.-H.; Yusa, R.; Baldwin, B.W.
Tetrahedron Lett. 2003, 44, 1831.
1
Received in the UK March 30, 2004