An easy and fast method for oxidative deprotection of trimethylsilyl ethers, tetrahydropyranyl ethers, and ethylene acetals with KMnO4 supported on alumina under solvent-free conditions

Article abstract of DOI:10.1081/SCC-120002518

A manipulatively simple and rapid method for oxidation deprotection of trimethylsilyl ethers, tetrahydropyranyl ethers and deprotection of ethylene acetals to afford carbonyl compounds under solvent-free conditions in the presence or absence of alumina with potassium permanganate.

Full text of DOI:10.1081/SCC-120002518

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AN EASY AND FAST METHOD FOR OXIDATIVE
DEPROTECTION OF TRIMETHYLSILYL ETHERS,
TETRAHYDROPYRANYL ETHERS, AND ETHYLENE
ACETALS WITH KMnO SUPPORTED ON ALUMINA
4
UNDER SOLVENT-FREE CONDITIONS
a
a
b
a
A. R. Hajipour , S E. Mallakpour , I. M. Baltork & H. Backnezhad
a
Pharmaceutical Research Laboratory , College of Chemistry , Isfahan University of
Technology , Isfahan, IR, 84156, Iran
b
Department of Chemistry , Isfahan University , Isfahan, IR, 81744, Iran
Published online: 16 Aug 2006.
To cite this article: A. R. Hajipour , S E. Mallakpour , I. M. Baltork & H. Backnezhad (2002) AN EASY AND FAST METHOD
FOR OXIDATIVE DEPROTECTION OF TRIMETHYLSILYL ETHERS, TETRAHYDROPYRANYL ETHERS, AND ETHYLENE ACETALS WITH
KMnO SUPPORTED ON ALUMINA UNDER SOLVENT-FREE CONDITIONS, Synthetic Communications: An International Journal
4
for Rapid Communication of Synthetic Organic Chemistry, 32:5, 771-779, DOI: 10.1081/SCC-120002518
To link to this article: http://dx.doi.org/10.1081/SCC-120002518
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SYNTHETIC COMMUNICATIONS, 32(5), 771–779 (2002)
AN EASY AND FAST METHOD FOR
OXIDATIVE DEPROTECTION OF
TRIMETHYLSILYL ETHERS,
TETRAHYDROPYRANYL ETHERS, AND
ETHYLENE ACETALS WITH KMnO4
SUPPORTED ON ALUMINA UNDER
SOLVENT-FREE CONDITIONS
1
,
1,
2
A. R. Hajipour, * S. E. Mallakpour, * I. M. Baltork,
1
and H. Backnezhad
1
Pharmaceutical Research Laboratory, College of
Chemistry, Isfahan University of Technology,
Isfahan, 84156, IR, Iran
Department of Chemistry, Isfahan University,
2
Isfahan 81744, IR, Iran
ABSTRACT
A manipulatively simple and rapid method for oxidation
deprotection of trimethylsilyl ethers, tetrahydropyranyl ethers
and deprotection of ethylene acetals to afford carbonyl com-
pounds under solvent-free conditions in the presence or
absence of alumina with potassium permanganate.
*
Corresponding authors. E-mail: haji@cc.iut.ac.ir
7
71
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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7
72
HAJIPOUR ET AL.
The protection and deprotection of the hydroxy functional groups can
1
play an essential role in synthetic strategy. The transformation of alcohols
to the corresponding trimethylsilyl ethers is a very common way to protect
hydroxy groups.
reported for oxidative cleavage of trimethylsilyl ethers to the corresponding
1
–3
In recent years a wide variety of methods have been
4
–7
carbonyl compounds,
but some of the mentioned methods encounter
drawbacks such as the requirement for aqueous reaction conditions, use
of expensive reagents, long reaction times, low yields of the products and
tedious work-up. Therefore, introduction of new methods and inexpensive
reagents for such functional group transformations is still in demand.
The tetrahydropyranyl (THP) group is one of the most frequently used
1
,8
groups to protect alcohols and phenols.
stability of tetrahydropyranyl ether under a variety of reaction conditions,
,4-dihydro-2H-pyran is still a reagent of choice for protection of the
Owing to the outstanding
3
9
hydroxyl group in peptide, nucleotide and carbohydrate chemistry. Since
direct transformation of tetrahydropyranyl ethers to their carbonyl com-
5
,7,10–13
pounds is rare in the literature,
desirable. Acetal formation is the most widely used protecting method for
introduction of new methods is
1
aldehydes and ketones, however, deprotection of acetals and ketals to the
corresponding carbonyl compound is a useful transformation in organic
1
3–18
synthesis.
Heterogeneous reactions that are facilitated by supported reagents
1
9
on various inorganic surfaces have recently attracted attention. The
most advantage of these methods over conventional classical method
is that they show cleaner reactions, decreased reaction time and easier
work-up. In continuation of our ongoing program to develop environ-
2
0
mentally benign methods using solid supports, we wish to report a
novel and efficient method for the oxidative deprotection of trimethyl-
silyl and tetrahydropyranyl ethers to the corresponding carbonyl com-
pounds by with potassium permanganate (Scheme 1 and Table 1). This
oxidizing reagent is an inexpensive, water-soluble and stable oxidizing
reagent that is commercially available. This solvent is insoluble in non-
aqueous solvents; however, the requirement of aqueous conditions had to
be overcome.
Scheme 1.

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773
Table 1. Oxidative Deprotection of Trimethylsilyl and Tetrahydropyranyl Ethers
with Supported KMnO
4
Time
(min)
Yield
a
(%)
Entry
Substrate
OTMS
Product
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
PhCH
2
PCHO
2-MeOC
3-MeOC
10
10
15
20
10
99
3
20
15
10
5
20
20
10
10
15
10
15
10
10
93
80
80
95
75
2-MeOC
3-MeOC
6
H
H
4
CH
CH
2
OTMS
OTMS
6
6
H
H
4
CHO
CHO
6
4
2
4
3-O NC H CH OTMS
2
3-O NC H CHO
2 6 4
6
4
2
2,5-(MeO)
PhCH(Me)OTMS
4-ClC H CH(Me)OTMS
2
C
H
6 3
CH
2
OTMS
2 6 3
2,5-(Me) C H CHO
PhCOMe
15
4-ClC H COMe
6
99
92
90
95
95
75
82
90
90
88
90
98
94
86
6
4
4
Ph
4-PhC
a-TetralolTMS
PhCH OTHP
2-MeOC CH
3-MeOC H CH OTHP
2
CHOTMS
Ph
2
CO
6
4
H CH(Me)OTMS
6 4
4-PhC H COMe
1
1
1
1
1
1
1
1
1
1
2
a-Tetralone
PhCHO
2
H
6 4
2
OTHP
2-MeOC
3-MeOC H CHO
6
4
H CHO
6
4
2
6
4
4-MeOC H CH OTHP
4
4-MeOC H CHO
4
6
2
6
3,4-(MeO)
2
C
C
6
H
H
3
CH
CH
2
OTHP
OTHP
3,4-(MeO)
2,5-(MeO)
PhCOMe
2
C
6
H
H
3
CHO
CHO
62,5-(MeO)
2
6
3
2
2
C
6
3
7
8
9
0
PhCH(Me)OTHP
4-ClC CH(Me)OTHP
Ph CHOTHP
a-TetralolTHP
6
H
4
4-ClC
Ph CO
a-Tetralone
6 4
H COMe
2
2
a
Yields based on the isolated products after column chromatography.
In order to evaluate the effect of alumina in this reaction we tried the
oxidative deprotection of trimethylsilyl and tetrahydropyranyl ethers with
potassium permanganate without using alumina. The rate of the reaction in
the absence of alumina is slower and the yield is lower (Table 2).
Potassium permanganate was also used to transform ethylene
acetals to the corresponding carbonyl compounds under solvent free
conditions in excellent yields (Scheme 2 and Table 3). Again the yield
Scheme 2.

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74
HAJIPOUR ET AL.
Table 2. Oxidative Deprotection of Trimethylsilyl and Tetrahydropyranyl Ethers
with KMnO
Entry
4
Time
(min)
Yield
a
Substrate
OTMS
Product
(%)
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
PhCH
2
PCHO
2-MeOC
3-MeOC
25
30
35
30
35
70
25
35
25
25
40
35
30
30
25
30
35
30
30
35
75
70
70
55
70
2-MeOC
3-MeOC
6
H
H
4
CH
CH
2
OTMS
OTMS
6
H
H
4
CHO
CHO
6
4
2
6
4
3-O NC H CH OTMS
2
3-O NC H CHO
2 6 4
6
4
2
2,5-(MeO)
PhCH(Me)OTMS
2
C
6
3
H CH
2
OTMS
2 6 3
2,5-(Me) C H CHO
PhCOMe
25
4-ClC H CH(Me)OTMS
6
4-ClC H COMe
6
80
77
80
75
45
60
55
60
65
60
55
75
69
72
4
4
Ph
4-PhC
a-TetralolTMS
PhCH OTHP
2-MeOC CH
3-MeOC H CH OTHP
2
CHOTMS
Ph
2
CO
6
H
4
CH(Me)OTMS
6 4
4-PhC H COMe
1
1
1
1
1
1
1
1
1
1
2
a-Tetralone
PhCHO
2
H
6 4
2
OTHP
2-MeOC
3-MeOC H CHO
6 4
H CHO
6
4
2
6
4
4-MeOC H CH OTHP
6
4-MeOC H CHO
6
4
2
4
3,4-(MeO)
2
C
6
H
H
3
CH
CH
2
2
OTHP
OTHP
3,4-(MeO)
2,5-(MeO)
PhCOMe
2
C
6
H
H
3
CHO
CHO
62,5-(MeO)
2
C
6
3
2
C
6
3
7
8
9
0
PhCH(Me)OTHP
4-ClC CH(Me)OTHP
Ph CHOTHP
a-TetralolTHP
6
H
4
4-ClC
Ph CO
a-Tetralone
6 4
H COMe
2
2
a
Yields based on the isolated products after column chromatography.
of transformation of ethylene acetals to the corresponding carbonyl
compounds with potassium permanganate without using alumina is lower
and also the rate is slower (Table 4). The cinnamaldehyde acetal as an
allylic carbonyl compound derivative was not converted to its corres-
ponding aldehyde properly with this reagent, and many by-products
were obtained. Interestingly, overoxidation of the products was not
observed by this method. In comparison to benzylic trimethylsilyl
ethers, benzylic tetrahydropyranyl ethers and benzylic ethylene acetals, oxi-
dation deprotection of aliphatic trimethylsilyl ethers and aliphatic
tetrahydropyranyl ethers or deprotection of aliphatic ethylene acetals
with this reagent does not occur at all. Therefore this reagent is not
suitable for oxidation deprotection of aliphatic trimethylsilyl ethers and
aliphatic tetrahydropyranyl ethers or deprotection of aliphatic ethylene
acetals.

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775
Table 3. Deprotection of Ethylene Acetals with Supported KMnO4
Time
(min)
Yield
(%)
b
Entry
Substrate
Product
1
2
Acetophenoneethylene acetal Acetophenone
2-Methoxybenzaldehyde-
ethylene acetal
5
15
98
92
2-Methoxybenzaldehyde
3
4
5
2-Nitrobenzaldehydeethylene 2-Nitrobenzaldehyde
acetal
15
15
75
85
2-Chloroacetophenone-
ethylene acetal
2-Chloroacetophenone
a-Tetraloneethylene acetal
4-Phenylacetophenone-
ethylene acetal
a-Tetralone
4-Phenylacetophenone
10
15
90
85
6
a
Yields based on the isolated products after purification with column
chromatography.
Table 4. Deprotection of Ethylene Acetals with KMnO4
Time
(min)
Yield
(%)
a
Entry
Substrate
Product
1
2
Acetophenoneethylene acetal
2-Methoxybenzaldehyde-
ethylene acetal
Acetophenone
2-Methoxybenzaldehyde
25
35
68
70
3
4
5
2-Nitrobenzaldehydeethylene
acetal
2-Chloroacetophenone-
ethylene acetal
2-Nitrobenzaldehyde
2-Chloroacetophenone
35
40
55
55
a-Tetraloneethylene acetal
4-Phenylacetophenoneethylene
acetal
a-Tetralone
4-Phenylacetophenone
40
35
20
50
6
a
Yields based on the isolated products after purification with column
chromatography.
In summary, in this study we introduced a new and cheap method-
ology for the oxidative deprotection of trimethylsilyl and tetrahydropyranyl
ethers and deprotection of ethylene acetals to the corresponding carbonyl
compounds in high yields under solvent-free conditions. The low price of
the reagent, easy work-up, mild reaction conditions, and high yield of the
products, make this method a novel and useful method for the oxidative

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7
76
HAJIPOUR ET AL.
deprotection of trimethylsilyl and tetrahydropyranyl ethers and deprotection
of ethylene acetals to afford corresponding carbonyl compounds.
EXPERIMENTAL
Oxidative Deprotection of Trimethylsilyl and Tetrahydropyranyl
Ethers with Supported KMnO Under Solvent-Free Conditions
4
General Procedure
The alumina supported permanganate is prepared by grinding
KMnO (4 g, 25.3 mmol) and alumina (Al O , neutral, 5 g) in a mortar
4
2
3
and with a pestle until a fine, homogenous, purple powder is obtained. In
a mortar trimethylsilyl ether or tetrahydropyranyl ether (2 mmol) was
added to KMnO /Al O (1.0 g, 2.8 mmol) and the mixture was ground
4
2
3
with a pestle in a mortar until TLC showed complete disappearance of
trimethylsilyl ether or tetrahydropyranyl ether (Table 1). The reaction
progress was monitored by TLC (eluent : cyclohexane/EtOAc: 8 : 2). Then
acetone (15 ml) was added to the reaction mixture and after vigorous
stirring, the mixture was filtered off. The acetone was evaporated by
rotary evaporator and the residue was taken up into ether (10 ml) which
was evaporated to give the crude material. The resulting crude material was
purified by a column chromatography on silica gel using a mixture of hexane
and ethyl acetate as eluent (90 : 10).
Oxidative Deprotection of Trimethylsilyl and Tetrahydropyranyl
Ethers with KMnO Under Solvent-Free Conditions
4
General Procedure
In a mortar trimethylsilyl ether or tetrahydropyranyl ether (2 mmol)
was added to KMnO (0.44 g, 2.8 mmol) and the mixture was ground with
4
a pestle in a mortar until TLC showed complete disappearance of trimethyl-
silyl ether or tetrahydropyranyl ether (Table 2). The reaction progress was
monitored by TLC (eluent : cyclohexane/EtOAc: 8 : 2). Then acetone (15 ml)
was added to the reaction mixture and after vigorous stirring, the mixture
was filtered off and the acetone was evaporated by rotary evaporator. The
residue was taken up into ether (10 ml) which was evaporated to give
the crude material. The resulting crude material was purified by a column

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OXIDATIVE DEPROTECTION
777
chromatography on silica gel using a mixture of hexane and ethyl acetate as
eluent (90 : 10).
Deprotection of Ethylene Acetals with Supported KMnO4
Under Solvent-Free Conditions
General Procedure
In a mortar ethylene acetal or ketal (2 mmol) was added to KMnO4/
Al O (1.0 g, 2.8 mmol) and the mixture was ground with a pestle in a
2
3
mortar until TLC showed complete disappearance of ethylene acetal or
ketal (Table 3). The reaction progress was monitored by TLC (eluent :
cyclohexane/EtOAc: 8 : 2). Then acetone (15 ml) was added to the reaction
mixture and after vigorous stirring, the mixture was filtered off. The acetone
was evaporated by rotary evaporator and the residue was taken up into
ether (10 ml) which was evaporated to give the crude material. The resulting
crude material was purified by a column chromatography on silica gel using
a mixture of hexane and ethyl acetate as eluent (90 : 10).
Deprotection of Ethylene Acetals with Supported KMnO4
Under Solvent-Free Conditions
General Procedure
In a mortar ethylene acetal or ketal (2 mmol) was added to KMnO4
0.44 g, 2.8 mmol) and the mixture was ground with a pestle in a mortar until
(
TLC showed complete disappearance of ethylene acetal or ketal (Table 4).
The reaction progress was followed by TLC (eluent : cyclohexane/EtOAc:
8
: 2). Then acetone (15 ml) was added to the reaction mixture and after
vigorous stirring, the mixture was filtered off. The acetone was evaporated
by rotary evaporator and the residue was taken up into ether (10 ml). The
ether was evaporated to give the crude material. The resulting crude
material was purified by a column chromatography on silica gel using a
mixture of hexane and ethyl acetate as eluent (90 : 10).
ACKNOWLEDGMENT
The authors are thankful of the Isfahan University of Technology
IUT), I.R. Iran for the financial support.
(

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HAJIPOUR ET AL.
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Received in Japan October 2, 2000

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