Efficient, selective deprotection of aromatic acetates catalyzed by Amberlyst-15 or iodine

Article abstract of DOI:10.1016/S0040-4039(03)01298-X

Aromatic acetates were selectively deprotected in the presence of aliphatic acetates to the corresponding phenols in excellent yields using Amberlyst-15 or iodine as catalysts in methanol at room temperature. The first catalyst can be recovered.

Full text of DOI:10.1016/S0040-4039(03)01298-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5465–5468
Efficient, selective deprotection of aromatic acetates catalyzed
ꢀ
by Amberlyst-15 or iodine
Biswanath Das,* Joydeep Banerjee, R. Ramu, Rammohan Pal, N. Ravindranath and C. Ramesh
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 28 March 2003; revised 12 May 2003; accepted 22 May 2003
Abstract—Aromatic acetates were selectively deprotected in the presence of aliphatic acetates to the corresponding phenols in
excellent yields using Amberlyst-15 or iodine as catalysts in methanol at room temperature. The first catalyst can be recovered.
©
2003 Elsevier Science Ltd. All rights reserved.
Phenolic hydroxy groups are present in several bioac-
tive naturally occurring compounds, hence protection
and subsequent deprotection of this group is necessary
for multistep transformations and syntheses of these
We have recently discovered a simple process for facile
cleavage of aromatic acetates over a wide range of
functional groups in the presence of Amberlyst-15 or
iodine as catalysts in methanol. Several aromatic
acetates were selectively deprotected to the correspond-
ing phenols (Table 1) using these catalysts at room
temperature. The yields of the regenerated phenols were
typically excellent. Alkyl acetates were unaffected by
both catalysts under the present experimental condi-
tions. Ethers, esters and lactones also remained unaf-
fected. Amberlyst-15 showed similar activity towards
the deprotection of aromatic acetates containing elec-
tron-donating and electron-withdrawing groups but
iodine showed weak or no activity towards deprotec-
tion of aromatic acetates possessing electron-withdraw-
ing groups (except when in the presence of another
1
compounds. A routinely used method for the protec-
tion of the phenolic hydroxy group involves conversion
to the corresponding acetate which can be cleaved1
under acidic or basic conditions or by hydrogenolysis.
However, these deprotection methods may affect differ-
ent sensitive functional groups and selectivity is poor. A
limited number of methods exist for the selective depro-
tection of aromatic acetates in the presence of aliphatic
2
a
acetates (these include the use of specific micelles,
2
b
2c
2d
Zn–MeOH, cyclodextrin, metalloenzymes, metal
complexes, antibodies and NH OAc ). Although
2
e
2f
2g
4
these methods have certain applicabilities most have
associated drawbacks such as operational complexity,
harsh reaction conditions, use of costly and difficult to
obtain reagents, long reaction times and low yields. The
recovery of catalysts is also a problem. Recently natural
–
OAc group). Thus, p-nitrophenyl acetate (entry g) was
easily converted into p-nitrophenol (time 3.0 h, yield
7%) using Amberlyst-15 but was unaffected in the
8
presence of iodine. Amberlyst-15 also showed high
chemoselectivity for the cleavage of phenyl acetates
without affecting electron-withdrawing groups such as
an aldehyde, ketone, benzoate, N-acetyl and tosylate.
To demonstrate the selectivity, some intermolecular
experiments were also carried out. Thus, when a mix-
ture of p-methylphenyl acetate and phenylethyl acetate
in methanol (entry u) was treated with Amberlyst-15
and iodine separately, the first compound underwent
deprotection in each case to p-methylphenol, but the
second compound remained unchanged. However,
when the reaction was carried out with a mixture of
phenyl acetate and p-formylphenyl acetate (entry v) in
the presence of these two catalysts separately, both
compounds were deprotected with Amberlyst-15 but
only the first compound with iodine.
3
kaoline clay has been applied, however, the clay was
collected from a specific geographical region. Thus,
there is a need for suitable methods for selective depro-
tection of aromatic acetates which make use of readily
available catalysts and which work efficiently under
mild reaction conditions.
Keywords: aromatic acetates; deprotection; Amberlyst-15; iodine;
chemoselectivity.
ꢀ
Part 29 in the series, ‘Studies on Novel Synthetic Methodologies’.
*
Corresponding author: Tel: +91-40-7173874; fax: (91) 40-7160512;
e-mail: biswanathdas@yahoo.com
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01298-X

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B. Das et al. / Tetrahedron Letters 44 (2003) 5465–5468
The present method has also been utilized for the
deprotection of acetates of some naturally occurring
tion of aromatic acetates at room temperature via a
simple experimental procedure. The first catalyst
works under heterogeneous conditions and can easily
be removed from the reaction mixture simply by filtra-
tion and can be activated and reused.
6
4
bioactive phenols. Thus rhododendrol diacetate (entry
5
s) and diphyllin acetate (entry t) were converted into
rhododendrol monoacetate and diphyllin respectively in
very high yields. The first product can be utilized for
the preparation of various analogues of rhododendrol
with modifications at the phenolic hydroxyl group.
In conclusion, we have developed a mild, efficient and
facile process for the deprotection of aromatic acetates
using Amberlyst-15 and iodine as catalysts. The process
is associated with high yields of the parent phenols and
high chemoselectivity. The method is also useful for
The catalysts, Amberlyst-15 and iodine are readily
available and inexpensive. They catalyze the deprotec-
c
Table 1. Deprotection of aryl acetates with Amberlyst-15 and iodine

B. Das et al. / Tetrahedron Letters 44 (2003) 5465–5468
5467
Table 1. (Continued)
deprotection of the acetates of bioactive natural phe-
nols (chiral and non-chiral) containing sensitive func-
tional groups.
References
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Dorta, H. L.; Rodriguez, F. L. Tetrahedron Lett. 1981, 22,
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Acknowledgements
The authors thank CSIR and UGC, New Delhi for
financial assistance.

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Giorgi, I. B. J. Org. Chem. 1994, 59, 7602; (d) Cramp-
temperature. After completion of the reaction (TLC) the
catalyst was filtered off and washed with MeOH (2×5
ml). The filtrate was concentrated under reduced pres-
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3
4
5
6
(b) Treatment of aryl acetate with iodine: A mixture of
aryl acetate (1 mmol), MeOH (10 ml) and I (100 mg)
2
. Das, B.; Padma Rao, S.; Srinivas, K. V. N. S.; Yadav,
J. S. Phytochemistry 1993, 33, 2529.
. Murakami, T.; Matsushima, A. J. Pharm. Soc. Jpn.
was stirred at room temperature. The progress of the
reaction was monitored by TLC. After completion of the
reaction, MeOH was removed under reduced pressure
and the residue was extracted with EtOAc (3×10 ml).
The extract was washed with a solution of sodium thio-
sulfate (3×10 ml) and subsequently with water (3×10 ml).
The concentrated extract was subjected to column chro-
matography over silica gel to afford the parent phenol.
1
961, 81, 1596.
. Experimental procedure:
a) Treatment of aryl acetate with Amberlyst-15: Aryl
(
acetate (1 mmol) and Amberlyst-15 (100 mg) were taken
in MeOH (10 ml). The mixture was stirred at room