A cheap, simple, and versatile method for acetylation of alcohols and phenols and selective deprotection of aromatic acetates under solvent-free condition

Article abstract of DOI:10.1081/SCC-200048988

Acyclic and cyclic acetates of various alcohols and phenols were obtained in excellent yields under mild reaction conditions in the presence of a catalytic amount of sodium hydroxide under solvent-free conditions and microwave irradiation. Selective deprotection of acetate group from the corresponding phenolic compounds was carried out in the presence of LiClO₄· 2H₂O. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200048988

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A Cheap, Simple, and Versatile
Method for Acetylation of
Alcohols and Phenols and
Selective Deprotection of
Aromatic Acetates Under
Solvent‐Free Condition
a
a
Fatemeh Rajabi & Mohammad R. Saidi
a
Department of Chemistry, Sharif University of
Technology, PO Box 11365‐9516, Tehran, Iran
Version of record first published: 28 Jul 2007.
To cite this article: Fatemeh Rajabi & Mohammad R. Saidi (2005): A Cheap,
Simple, and Versatile Method for Acetylation of Alcohols and Phenols and Selective
Deprotection of Aromatic Acetates Under Solvent‐Free Condition, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:3, 483-491
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Synthetic Communications , 35: 483–491, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200048988
A Cheap, Simple, and Versatile Method for
Acetylation of Alcohols and Phenols and
Selective Deprotection of Aromatic Acetates
Under Solvent-Free Condition
Fatemeh Rajabi and Mohammad R. Saidi
Department of Chemistry, Sharif University of Technology, Tehran, Iran
Abstract: Acyclic and cyclic acetates of various alcohols and phenols were obtained in
excellent yields under mild reaction conditions in the presence of a catalytic amount of
sodium hydroxide under solvent–free conditions and microwave irradiation. Selective
deprotection of acetate group from the corresponding phenolic compounds was carried
out in the presence of LiClO .2H O.
4
2
Keywords: Acetylation, alcohols, phenols, deprotection, solvent-free
Protection and deprotection play a significant role in organic synthesis as
shown by many different methods, which have been developed for these
[
key transformation. Although few methods have been reported for the
1]
[
2]
selective deprotection of aromatic acetates, which are widely present in
natural occurring products. Deprotection of phenolic acetate is important in
multistep transformations and total synthesis.
Acetylation is one of the most common methods for the protecting of
hydroxyl group, because of its facile preparation and can be easily hydrolyzed
[
3]
by mild basic or acidic condition. Acetylation of hydroxyl groups is usually
carried out with acetic anhydride or acetyl chloride under basic or acidic
conditions. Many different methods for acetylation of alcohols under
[
4]
[5]
[6]
[7]
basic condition, such as pyridin,
DMAP,
Bu P,
3
MgBr -R N,
2 3
Received in India October 6, 2004
Address correspondence to Mohammad R. Saidi, Department of Chemistry, Sharif
University of Technology, PO Box 11365-9516, Tehran, Iran. E-mail: saidi@sharif.
edu

484
F. Rajabi and M. R. Saidi
[
8]
[9]
KF-Al O , amino phosphanes, SiO -NaHSO ,
[10]
have been reported. A
2
3
2
4
[11]
[12]
[16]
[21]
[26]
variety of acid catalysts acetylation reaction, such as TaCl ,
5
TMSOTf,
Cu(OTf)2,
Sn(OTf)3,
[
13]
[14]
[15]
COCl2,
In(OTf)3,
montmorillonite K-10 or KSF,
[19]
Sc(OTf)3,
[20]
TiCl(OTf)3,
[
17]
[18]
Li(OTf),
Cr(OTf) ,
La(OTf) ,
3
2
[
22]
[23]
[24]
[25]
Sn(NTf ) ,
2
WO ZrO ,
Bi(OTf)3,
were also reported in the literature.
lipase,
3
3
3
2
[
27]
[28]
molecular sieves,
and I2
Also pseudomonas cepacia PS lipase,
[
29]
[30]
zeolite HSZ-360,
[33]
twisted
have been used for
[
31]
[32]
amides,
chiral phosphines,
and iron complexes
the chemoselective acetylation. However, many of these methods have
problems such as difficulty in handling the reagents, using toxic and
hazardous solvents and are limited for wide applications. It was also found
that the same reaction with Ac O-Py/Al O was further accelerated by
2
2 3
[
34]
microwave irradiation.
In the recent years, application of microwave irradiation for rapid organic
synthesis as a superior, clean, and fast technique have found widespread use
[
35,36]
over the conventional heating reactions,
conditions which are gaining more widespread uses in organic
particularly under solvent-free
[37–41]
chemistry.
Considering the above reports and in continuation of our interests on
environmentally benign solvent-free synthetic reaction and microwave-
[
42–46]
assisted organic synthesis,
herein, we describe a very simple, fast,
and general protocol for the acetylation of alcohols with acetic anhydride
and a catalytic amount of sodium hydroxide under microwave irradiation
and solvent-free conditions.
When primary, secondary, and even tertiary alcohols were reacted with
Ac O in the presence of catalytic amounts of NaOH (ca. 0.2 equiv) under
2
microwave irradiation and solvent-free conditions, the corresponding
acetates were obtained in excellent yields. The same results were obtained
when phenolic compounds were reacted with Ac O in the presence of
2
0
.2 equiv of NaOH, under microwave irradiation for about 1 min, (Table 1
and Scheme 1). Moreover, allylic and propargylic alcohols, diols, or triol
underwent acetylation under these condition in excellent yields (Scheme 1,
Table 2).
We first examined the acetylation of benzyl alcohol, 1-phenyl ethanol,
and 2-naphthol using Ac O in the absence of NaOH under microwave
2
irradiation for 5 min. In these cases low yields (ca. 20%) of products were
obtained.
In continuation of our interest in using solid LiClO (Azizi and
4
[47–49]
Saidi,
for different organic transformations, we discovered that
phenolic acetates can be easily deprotected selectively by using solid
hydrated LiClO . We found out that solid hydrated LiClO is an efficient
4
4
reagent for selective deprotection of aryl acetates. Several aromatic acetates
were selectively deprotected to the corresponding phenols, but aliphatic
acetates were not transformed into their corresponding alcohols even after a

Acetylation of Alcohols and Phenols
485
Table 1. Acylating hydroxy group with Ac O/NaOH under MW irradation
2
Time
(sec)
Yield
(%)
Entry
1
Substrate
Product
60
92
2
PhCH
2
OH
PhCH
2
OAc
45
99
3
4
Ph(CH
2
)
3
OH
Ph(CH
2
)
3
OAc
40
75
99
94
5
6
7
8
9
CH
3
(CH
2
)
5
OH
CH
3
(CH
2
)
5
OAc
70
60
70
60
90
99
99
97
99
92
4-MeOC
6
H
5
CH
2
OH
4-MeOC
6
H
5
CH
2
OAc
4-CIC H CH OH
6
4-CIC H CH OAc
6 5 2
5
2
PhCH 55 CHCH OH
2
PhCH 55 CHCH OAc
2
1
0
90
92
11
12
13
HOCH
2
CH
2
OH
AcOCH
2
CH
2
OAc
70
80
75
99
92
99
HO(CH ) OH
3
AcO(CH ) OAc
2 3
2
14
15
16
17
18
19
20
21
C
6
H
5
OH
C
6
H
5
OAc
60
45
45
50
90
90
60
50
99
99
99
99
99
99
99
99
4-ClC
6
H
5
OH
6 5
4-ClC H OAc
4-O NC
2
6
H
5
OH
2 6 5
4-O NC H OAc
4-BrC H OH
6
4-BrC H OAc
6
5
5
4-BrC
4-ClC
6
H
5
OH
OH
4-BrC
4-ClC
6
H
5
OAc
OAc
6
H
5
6 5
H
2
2
2
3
40
45
99
99
(
continued)

486
F. Rajabi and M. R. Saidi
Table 1. Continued.
Time
(sec)
Yield
(%)
Entry
Substrate
Product
24
45
99
2
2
2
5
6
7
60
50
65
99
99
98
Scheme 1.
long reaction time. For example, when benzyl acetate is used for deacetylation
.
in the presence of LiClO4 2H O, no benzyl alcohol can be obtained even after
2
1
2 h (Scheme 2, Table 2).
In conclusion, the results obtained in this study reveal that a clean, fast,
simple, efficient, environmentally benign and solvent-free acetylation of
hydoxyl groups can be carried out with Ac O and small amount of sodium
2
hydroxide which is a very cheap and common reagent (although, a solvent
was used in the workup step). This method also is very useful for acetylation
of hydroxyl compounds that have an acid-sensitive group such as OMe and for
diols and triol. Also we have found that solid hydrated lithium perchlorate,
which is used as a cheap and recyclable reagent in comparism with many
other Lewis acid, is a simple and efficient reagent for selective deprotection
of aryl acetates.
EXPERIMENTAL
NMR spectra were recorded on a Bruker ACF 500 using chloroform-d as solvent.
Infrared spectra (IR) were measured on a Perkin-Elmer 1600 FT-IR spec-
trometer. Column chromatography was performed on silica gel, Merck grade
60. CH Cl or ether was distilled before use. Lithium perchlorare was
2 2
purchased from Across. Other chemicals were purchased from Fluka and Merck.
Scheme 2.

Acetylation of Alcohols and Phenols
487
Table 2. Deprotection of acetyl group from aromatic acetate by solid LiClO4
a
Entry
1
Substructure
Product
Time (hr)
2.5
Yield (%)
68
2
3
2.5
3.0
71
57
4
5
6
3.0
3.0
3.0
65
60
52
7
3.5
55
8
9
3.0
3.5
61
62
1
1
0
1
3.5
12
60
b
0.0
a
b
Isolated yields.
The same results were obtained for the other aliphatic acetates.
General Procedure for Acetylation of Hydroxyl Groups with NaOH
Under Solvent-free Condition
A mixture of alcohols, diols, or phenols (5 mmol), acetic anhydride
(
1
10–30 mmol, depending on the alcohol) , and NaOH (1–3 mmol,
1
depending on the alcohol) were placed in a sealed teflon container (screw
cap type, 50 ml) and subjected to microwave irradiation in a conventional
1
For alcohols 10 mmol of acetic anhydride and 10 mmol of NaOH was used; for diol
0 mmol of acetic anhydride and 20 mmol of NaOH was used; for triol 30 mmol of
2
acetic anhydride and 30 mmol of NaOH was used.

488
F. Rajabi and M. R. Saidi
microwave oven with 30–40% of high power for 1 to 2 min (Table 1). After
cooling, the mixture was diluted with CH Cl (20 mL) and washed with water
2
2
(
2 Â 20 mL), dried over MgSO , and evaporated to give the crude products.
4
Further purification was carried out by column chromatography on basic
alumina eluting with ethyl acetate/hexane, if needed. All compounds were
characterized on the basis of spectroscopic data (IR, NMR, MS) and by
comparison with those reported in the literature.
General Procedure for Deprotection of Aromatic Acetates Using
.
LiClO4 2H O Under Solvent-free Condition
2
.
Aromatic acetate (2 mmol), LiClO4 2H O (2 mmol), and MeOH (2 mmol)
2
were placed in a 5 mL flask and stirred at room temperature for the time
shown in Table 2. After the reaction was complete, dichloromethane
(10 mL) was added and the precipitated LiClO was recovered by filtration.
4
The filtrate was extracted with 5% sodium hydroxyl (2 Â 20 mL). After neu-
tralizing with 5% HCl, the product was extracted with dichloromethane
(
2 Â 10 mL), dried with MgSO . The solvent removed by using a rotary evap-
4
orator. Further purification was carried out by column chromatography on
basic alumina eluting with ethyl acetate/hexane, if needed. All compounds
were characterized on the basis of spectroscopic data (IR, NMR, MS) and
by comparison with those reported in the literature.
ACKNOWLEDGMENT
We are grateful to the Sharif University of Technology Research Council for
financial support of this research.
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