An efficient method for selective deprotection of trimethylsilyl ethers, tetrahydropyranyl ethers, ethylene acetals, and ketals under microwave irradiation

Article abstract of DOI:10.1081/SCC-120002408

1-Benzyl-4-aza-1-azoniabicyclo [2.2.2] octane dichromate (BAABOD) is a useful reagent for the selective cleavage of trimethylsilyl ethers, tetrahydropyranyl ethers, ethylene acetals and ketals to their corresponding alcohols, aldehydes and ketones. This method is very simple and efficient and the reaction has been carried out under microwave irradiation.

Full text of DOI:10.1081/SCC-120002408

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AN EFFICIENT METHOD FOR SELECTIVE
DEPROTECTION OF TRIMETHYLSILYL ETHERS,
TETRAHYDROPYRANYL ETHERS, ETHYLENE ACETALS,
AND KETALS UNDER MICROWAVE IRRADIATION
a
b
c
a
A. R. Hajipour , S. E. Mallakpour , I. Mohammadpoor-Baltork & S. Khoee
a
Pharmaceutical Research Laboratory , College of Chemistry , Isfahan University of
Technology , Isfahan, 84156, I.R. Iran
b
Pharmaceutical Research Laboratory , College of Chemistry , Isfahan University of
Technology , Isfahan, 84156, I.R. Iran
c
Department of Chemistry , Isfahan University , Isfahan, 81744, I.R. Iran
Published online: 16 Aug 2006.
To cite this article: A. R. Hajipour , S. E. Mallakpour , I. Mohammadpoor-Baltork & S. Khoee (2002) AN EFFICIENT METHOD
FOR SELECTIVE DEPROTECTION OF TRIMETHYLSILYL ETHERS, TETRAHYDROPYRANYL ETHERS, ETHYLENE ACETALS, AND
KETALS UNDER MICROWAVE IRRADIATION, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 32:4, 611-620, DOI: 10.1081/SCC-120002408
To link to this article: http://dx.doi.org/10.1081/SCC-120002408
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SYNTHETIC COMMUNICATIONS, 32(4), 611–620 (2002)
AN EFFICIENT METHOD FOR
SELECTIVE DEPROTECTION OF
TRIMETHYLSILYL ETHERS,
TETRAHYDROPYRANYL ETHERS,
ETHYLENE ACETALS, AND
KETALS UNDER MICROWAVE
IRRADIATION
1
,
1,
A. R. Hajipour, * S. E. Mallakpour, *
2
I. Mohammadpoor-Baltork, and S. Khoee
1
1
Pharmaceutical Research Laboratory,
College of Chemistry, Isfahan University of
Technology, Isfahan, 84156, I.R. Iran
Department of Chemistry, Isfahan University,
Isfahan, 81744, I.R. Iran
2
ABSTRACT
1
(
-Benzyl-4-aza-1-azoniabicyclo[2.2.2]octane dichromate
BAABOD) is a useful reagent for the selective cleavage of
trimethylsilyl ethers, tetrahydropyranyl ethers, ethylene acet-
als and ketals to their corresponding alcohols, aldehydes and
ketones. This method is very simple and efficient and the
reaction has been carried out under microwave irradiation.
*
Corresponding authors.
6
11
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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HAJIPOUR ET AL.
Trimethylsilyl ether, tetrahydropyranyl ether, ethylene acetals and
ketals are widely used as protective groups during the synthesis of natural
1
–3
compounds. A wide variety of methods are available for the conversion
of alcohols to their trimethylsilyl ethers and tetrahydropyranyl ethers and
much attention has been paid to the deprotection of these derivatives to give
the parent alcohol or to give their corresponding carbonyl compounds via
4
–18
oxidative cleavage of the protected groups.
acetals and ketals to their carbonyl compounds under non aqueous and
Deprotection of ethylene
1
9–21
aprotic conditions is also very important in organic synthesis.
In the
course of studies on the synthesis of biologically interesting natural prod-
ucts, a mild, fast and efficient method was required for the selective removal
of the carbonyl or alcohol groups without any change in the other func-
tional groups in polyfunctional molecules.
In recent years, there has been a growing interest in the application of
2
2–25
microwave irradiation in chemical reaction enhancement,
cleaner reactions, decreased reaction time and easier work-up. In a conti-
because of its
2
6
nuation of our ongoing efforts in this area, herein we wish to report a facile
method for the conversion of trimethylsilyl ether and tetrahydropyranyl
ether and deprotection of ethylene acetals and ketals to their alcohol com-
pounds under microwave irradiation.
Recently we have introduced 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]-
octane dichromate (BAABOD) 3 for the oxidation of alcohols to their
2
7
corresponding carbonyl compounds under microwave irradiation. This
new reagent has been readily prepared by reaction of an aqueous solution
of 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octane chloride 2 with CrO in 3 N
3
solution of HCl at room temperature as shown in Scheme 1. The resulting
Scheme 1.
orange powder, which can be stored for months without loss of activity, is
soluble in acetonitrile, acetone and N,N-dimethylformamide and slightly
soluble in chloroform, ethylacetate and dichloromethane, but is not soluble
in carbon tetrachloride, n-hexane and diethylether.

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DEPROTECTION UNDER MICROWAVE IRRADIATION
613
In this article we use this reagent for the deprotection of TMS-
and THP-protected molecules to their corresponding alcohols under micro-
wave irradiation. One equimolar of TMS- or THP-protected alcohols 4a–4l
was mixed with 3 in a mortar and ground with a pestle until the formation of
a homogeneous mixture. Then the reaction mixture was transferred to an
Erlenmeyer flask and was irradiated by microwave oven, until TLC showed
complete disappearance of starting material. But during the solid phase
irradiation, the reagent was destroyed gradually and the starting material
remained intact. So, we decided to use a solvent, which can play three
important roles: 1) as a primary absorber, 2) as a solvent for both the
reagent and the product 3) as a factor for increasing the dielectric constant
of the medium. By increasing the dielectric constant, the coupling with
microwave increased. We tested several solvents such as CCl , n-hexane,
4
toluene, o-cresol, acetonitrile and dichloromethane. The reaction failed to
proceed in hexane and toluene, since they do not couple and therefore do
not heat with microwave irradiation. So they are microwave inactive sol-
vents. o-Cresol and acetonitrile are microwave active solvents, but during
the reaction the starting material and the solvent were both degraded by
reagent and produced several by products. Finally we choose dichloro-
methane, as a solvent which is microwave active and also does not interfere
during the reaction processing. Therefore 1.5 mL of dichloromethane was
added to one equimolar amount of TMS- or THP- protected alcohols 4a–4l
and reagent 3. The mixture was irradiated with microwave oven, until TLC
showed complete disappearance of starting materials (Scheme 2). Following
the reaction by TLC shows that by disappearing of starting material spot,
Scheme 2.
the corresponding alcohols appeared as the only product and no by-product
was observed. The reaction was completed within 3–4 min and the pure alco-
hols were obtained by a simple work-up without further purification. The
results illustrated in Table 1 indicate that the reaction can be used for a variety
of TMS- and THP-protected primary and secondary benzylic alcohols.
In order to evaluate the effect of the microwave irradiation in this
reaction, we tried the reaction of 2-nitrobenzyl alcohol TMS ether with

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HAJIPOUR ET AL.
Table 1. Deprotection of Tetrahydropyranyl (THP) and Trimethylsilyl (TMS)
a
Ethers 4a–4l with Reagent 3 Under Microwave Irradiation
reagent 3 without using any microwave irradiation. The reaction did not
proceed at all after 60 min, grinding of the reaction mixture. The mechanism
of the reaction is reported by us for the oxidation of alcohol by this
2
7
reagent.

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DEPROTECTION UNDER MICROWAVE IRRADIATION
615
Deprotection of ethylene acetals and ketals to their carbonyl com-
pounds were also performed under same conditions. The reactions were
completed within 3–4 min and the pure aldehydes and ketones were
obtained by a simple work-up (Scheme 3 and Table 2).
Scheme 3.
Table 2. Deprotection of Ethylene Acetals and Ketals 6a–6i with Reagent 3 Under
a
Microwave Irradiation

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HAJIPOUR ET AL.
As we have reported in our previous work, microwave irradiation
is very effective to convert aliphatic and benzylic alcohols to their corre-
2
6b
sponding aldehydes and ketones, herein our new findings show that under
the same condition TMS-, THP-ether, ethylene acetals and ketals were
deprotected to their corresponding alcohols and carbonyl compounds
respectively. So, it is interesting to investigate the competitive reaction of
alcohols and the mentioned protected compounds with this reagent under
microwave irradiation. When we treated an equimolar amount of ethylene
ketal 6h with 3 in the 3,4-dimethoxybenzyl alcohol, the ketal 6h was selec-
tively deprotected and 3,4-dimethoxybenzyl alcohol was unchanged
(
Equation 1). When an equimolar amount of THP ether 4k in presence of
3,4-dimethoxybenzyl alcohol was treated with reagent 3, only the THP ether
4k was selectively deprotected to its corresponding alcohol (Equation 2).
Treatment of TMS ether 4f in the presence of 3,4-dimethoxybenzyl alcohol,
led to exclusive deprotection of TMS ether 4f to the corresponding alcohol
in 100% yield (Equation 3).

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617
In conclusion, we have developed a mild, fast and efficient method for
the cleavage of TMS-, THP-ether, ethylene acetals and ketals under micro-
wave irradiation, which is superior to previously reported methods in terms
of selectivity, high yield, purity of the products, simple and rapid work-up.
This method does not require a large excess of reagent and long reaction
time. Notably ether, nitro, halogen and double bond functional groups
present in the molecules were found to be resistant under the employed
conditions.
EXPERIMENTAL SECTION
General
Trimethylsilyl ethers, tetrahydropyranyl ethers, ethylene acetals were
1
5,16
prepared according to described procedures,
characterized by comparison of their spectral (IR, H-NMR), TLC and
physical data (melting and boiling point) with those of authentic
All of the products were
1
5
,12,20,27–29
samples. The reagent 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octane
2
dichromate (3) was prepared according to described procedures. All
H-NMR spectra were recorded at 90 MHz in CDCl and CCl relative to
3
7
1
4
TMS(0.00 ppm). All of the reactions were carried out in a hood with strong
ventilation. IR spectra were recorded on Shimadzu 435 IR spectrophoto-
meter. Spectra of solids were carried out using KBr pellets. Irradiation
was carried out in a domestic microwave oven (Samsung 2450 MHz
Watts), for an optimized time.
Deprotection of TMS-, THP-Ether
General Procedure
The deprotection of 2-nitrobenzyl alcohol TMS ether is representative
of the general procedure employed. In a mortar, a mixture of the protected
derivative 4c (0.39 g, 1.6mmol), 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octa-
nedichromate (1.00 g, 1.6mmol) was ground with a pestle in a mortar to
form a homogeneous mixture. After transferring the mixture to an Erlen-
meyer flask and adding 1.5 ml dichloromethane, it was irradiated with
microwave oven, until TLC (eluent: CCl ) showed complete disappearance
4
of starting materials (Table 1). Then CCl (15 ml) was added to the reaction
4
mixture and after vigorous stirring the mixture was filtered off and the

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HAJIPOUR ET AL.
solvent was evaporated by rotary evaporator. The pure 2-nitrobenzyl
alcohol was obtained and does not need further purification.
Deprotection of Ethylene Acetals and Ketals
General Procedure
The deprotection of 3-nitrobenzyl ethylene acetal 6c is representative
of the general procedure employed. The protected derivative 6c (0.28 g,
1
1
.61 mmol), 1-benzyl-4-aza-1-azoniabicyclo[2.2.2]octanedichromate (1.00 g,
.61 mmol) was crushed with a pestle in a mortar to form a homogeneous
mixture. After transferring the mixture to an Erlenmeyer flask and add-
ing 1.5 ml dichloromethane, it was irradiated with microwave oven, until
TLC (eluent: CCl ) showed complete disappearance of starting materials
4
(
Table 2). CCl (15 ml) was added to the reaction mixture and after vigorous
4
stirring, the mixture was filtered off and the solvent was evaporated by
rotary evaporator. The pure 3-nitrobenzaldehyde was obtained and does
not need further purification.
ACKNOWLEDGMENT
We are thankful to Research Council of the Isfahan University of
Technology (IUT) for the partial support of this work.
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3
Received in Japan December 20, 2000

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