V2O5-H2O2: A convenient reagent for the direct oxidation of acetals to esters

Article abstract of DOI:10.1016/S0040-4039(02)00982-6

Both cyclic and acyclic acetals were deprotected to give the corresponding aldehydes in acetonitrile, and are transformed to methyl esters in methanol, on treatment with a catalytic quantity of V₂O₅ and H₂O₂. Under identical conditions acid-sensitive alcohol protecting groups, such as tetrahydropyranyl and tert-butyldimethylsilyl ethers, were cleaved regenerating the corresponding alcohols.

Full text of DOI:10.1016/S0040-4039(02)00982-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 5123–5126
V2O5–H2O2: a convenient reagent for the direct oxidation of
acetals to esters
Rangam Gopinath, Alok Ranjan Paital and Bhisma K. Patel*
Department of Chemistry, Indian Institute of Technology, Guwahati 781 039, India
Received 27 March 2002; revised 16 May 2002; accepted 23 May 2002
Abstract—Both cyclic and acyclic acetals were deprotected to give the corresponding aldehydes in acetonitrile, and are
transformed to methyl esters in methanol, on treatment with a catalytic quantity of V2O5 and H2O2. Under identical conditions
acid-sensitive alcohol protecting groups, such as tetrahydropyranyl and tert-butyldimethylsilyl ethers, were cleaved regenerating
the corresponding alcohols. © 2002 Elsevier Science Ltd. All rights reserved.
Amongst the plethora of groups typically employed for
protecting aldehydes, acetals enjoy a cardinal position,
as exemplified by the numerous methods devised for
their attachment and removal.1 Direct conversion of
cyclic and acyclic acetals to esters is a useful synthetic
methodology in organic chemistry and numerous meth-
ods using a variety of reagents and conditions have
been developed. A comprehensive list of reagents for
the one-step transformation of an acetal to ester has
been compiled by Larock.2 These include O2, O2 under
photochemical conditions in the presence of Na2SO3,
O3, H2O2 in the presence of FeSO4, ROOH, (tBuO)2–
K2Cr2O7, tBuOOH, 3,3-dimethyldioxirane, NBS and
N2O4. Other reagents are also effective for this type of
transformation including peracetic acid,3 DDQ,4
tBuOOH-Pd(II) catalyst,5 sodium perborate,6 oxone,7
Co(II) catalyst,8 VO(OAc)2,9 H2O2 and HCl in alco-
a stronger oxidant than either hydrogen peroxide or
V2O5 and oxidises a variety of organic substrates.15
Recently, we have utilised it for the oxidative transfor-
mation of aldehydes to esters,14b in which, in order to
accelerate the reaction, a catalytic quantity of perchlo-
ric acid was added to the reaction medium. However,
the inherent acidity14a generated in the reaction medium
by the reaction of V2O5 and H2O2 was apparently
enough to bring about the esterifications although the
reaction rates were slow. We decided to test whether
the intrinsic acidity originating from V2O5–H2O2 is
sufficient to deprotect acid-sensitive protecting group
like acetals and to see if the resulting carbonyl com-
pound, in an alcoholic medium, could be converted into
the ester. In this letter, we describe a mild and efficient
method for the transformation of both cyclic and
acyclic acetals to carbonyl compounds when acetoni-
trile was used as solvent, and to esters when alcohol
was used. We also describe deprotection of other acid-
sensitive protecting groups such as THP and TBDMS
ethers under similar conditions.
hol,10 electrochemical oxidation,11 PPh3 BF3 , MTO–
H2O2.13 With a few exceptions, most of the methods
suffer from disadvantages such as ease of operation,
drastic conditions, long reaction times, use of excess
and expensive reagents. Furthermore, some methods
suffer from drawbacks like unsatisfactory yields in the
case of aromatic aldehydes bearing an electron-with-
drawing substituent in the aromatic ring, polymerisa-
tion of 2-furfural and an ineffective for aldehydes
containing double bonds.
+
− 12
As a test substrate for the oxidative transformation of
acetal to ester, benzaldehyde diethyl acetal 1 was cho-
sen. The reaction was performed by dissolving acetal (1
mmol) in methanol (3 mL) to which was added a
solution of V2O5 (0.04 mmol) dissolved in 30% H2O2 (4
mmol) under ice-cold conditions. The reaction times are
indicated for each substrate in Table 1.
We have been studying the activation of V2O5 using
hydrogen peroxide for different oxidation reactions.14
The peroxo-vanadium species generated upon treat-
ment of oxides of vanadium with hydrogen peroxide is
In most previous cases of acetal to ester transforma-
tion, the ester corresponding to the starting acetal were
obtained. However, in H2O2–HCl-mediated reactions,10
esters corresponding to solvent alcohol were obtained
via a transesterification mechanism. In our case, esters
* Corresponding author. E-mail: bkpatel@postmark.net
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00982-6

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R. Gopinath et al. / Tetrahedron Letters 43 (2002) 5123–5126
Table 1. Oxidative transformation of acetal to methyl ester with V2O5–H2O2
derived only from the solvent, but not by a transesterifi-
cation path. As expected, the acetal is first deprotected
to the corresponding carbonyl compound and the resul-
tant aldehyde is subsequently esterified by a mechanism
similar to that proposed earlier.14b
methodology, the reaction times were relatively shorter,
because esterification was directly from the aldehyde. In
addition, external acid was also added to the medium
because under acidic conditions, peroxo-vanadium spe-
cies, the active oxidising agent is stable and active.15a
An acidic medium also prolongs the lifetime of the
peroxo species of MeReO3 against reversible decompo-
sition.13 One of the drawbacks of the previous method-
ology was over-oxidation of some of the aldehydes
giving acids instead of esters. By the present methodol-
ogy aldehyde is slowly generated in situ from the acetal,
and no over-oxidised products were detected.
Treatment of a wide variety of acetals with V2O5–H2O2
in methanol gave the corresponding methyl esters in
high to excellent yields under mild reaction conditions.
Acyclic acetals 1 and 2 were converted to the corre-
sponding methyl esters, however acetal 3 and 9 contain-
ing an electron-withdrawing group were reluctant to
yield the ester, probably due to difficulty in regenera-
tion of the aldehyde, and also a high activation energy
for esterification.14b However, good yields were
achieved using a 10-fold excess of 30% H2O2 under
reflux conditions. Cyclic 1,3-dioxolanes 4–12 were con-
verted to the corresponding methyl esters in good
yields. Double-bond-containing substrate 13, which is
problematic and requires drastic conditions by other
methods, yielded an ester by this method. Esterification
of 2-furaldehyde in good yields further demonstrates
the efficacy of the methodology.
Since aldehyde generated in the reaction medium and in
the presence of methanol is converted to methyl ester,
we reasoned that by changing the solvent to acetonitrile
it should be possible to isolate the aldehyde. With this
objective, acetals (1 mmol) of various aldehydes in
acetonitrile (3 mL) were treated with a solution of V2O5
(0.04 mmol) dissolved in 30% H2O2 (4 mmol) under
ice-cold conditions. Aldehydes were regenerated from
both cyclic and acyclic acetals in less than 10 min. The
results are shown in Table 2. It is interesting to note
that the resultant aldehydes do not oxidised further
under this conditions, however, after a longer period of
time, aldehydes tended to be oxidised to the corre-
sponding acids.
In all the cases examined, reaction times were much
longer than in our earlier methodology.14b The present
one is a two-step process involving a deprotection step
followed by an esterification. The pH values recorded
at the beginning and after completion of the reaction
were ca. 1.86 and 2.06, respectively. In our earlier
All the acetals described to this point were symmetrical
and we thought it interesting to test the oxidation of

R. Gopinath et al. / Tetrahedron Letters 43 (2002) 5123–5126
5125
Table 2. Deprotection of acetals to aldehydes and THP and TBDMS ethers to corresponding alcohols with V2O5–H2O2
unsymmetrical acetals such as tetrahydropyranyl
derivatives of alcohols. It has been reported that THP
ethers when treated with neutral or basic oxidising
agents gave rise exclusively to the hydroxy esters2,6
while treatment with other acidic oxidants7,16 gave oxi-
dative deprotection. When tetrahydropyranyl ethers of
various alcohols were treated under identical conditions
with V2O5–30% H2O2 very poor yields of alcohols were
obtained. However, refluxing the reaction mixture can
accelerate the deprotection as shown for different tetra-
hydropyranyl ethers in Table 2. This observation shows
that tetrahydropyranyl ethers are more stable compared
to either cyclic or acyclic acetals. We further extended
this methodology for the deprotection of other acid-
sensitive protecting groups such as tert-butyldimethyl-
silyl (TBDMS) ethers. When TBDMS ethers 21 and 22
were treated with a solution of V2O5–30% H2O2, under
ice-cold conditions, alcohols were regenerated in good
yields. Surprisingly in the latter case along with the
benzyl alcohol some benzaldehyde was also detected,
which could originate from the over oxidation of the
resultant benzyl alcohol. The present study indicates
that TBDMS ethers are more labile compared to THP
ethers under acidic conditions, which is consistent with
our earlier observation.17
catalytic quantity and hydrogen peroxide is a cheap and
relatively safe oxidant, which produces only water as
the side product. Acetals can be converted to other
esters using different primary alcohols. Although proce-
dures already exist for conversion of aldehydes to
esters, the simplicity and low cost of our procedure
allow it to compete as a practical alternative.
(a) General procedure for the transformation of acetal to
ester:
Vanadium pentoxide (7.24 mg, 0.04 mmol) was added
to a 30% aq. solution of hydrogen peroxide (0.45 mL, 4
mmol) and left stirring at 0oC until all the vanadium
pentoxide dissolved and the solution became reddish
brown in colour (approx. 10 min). This was then added
to an ice-cold and stirred solution of acetal (1 mmol) in
methanol (3 mL). The resulting solution was stirred at
ꢀ5°C until TLC and GC detected no starting material.
The solvent was removed in vacuo and the residue
redissolved in ethyl acetate (20 mL). The organic layer
was first washed with 5% aq. sodium bicarbonate solu-
tion (5 mL) then with water (5 mL) and finally dried
over anhydrous Na2SO4. The solvent was removed in
vacuo and the residue was purified by column chro-
matography (silica gel, hexane:ethyl acetate) to afford
the product.
In conclusion, the present method represents a simple,
rapid way to oxidise acetals to esters and to deprotect
THP and TBDMS ethers. The reagent, V2O5, is used in

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R. Gopinath et al. / Tetrahedron Letters 43 (2002) 5123–5126
(b) General procedure for deprotection of tetra-
hydropyranyl and TBDMS ethers to alcohols:
4. Sviridov, A. F.; Ermolenko, M. S.; Yashunsky, D. V.;
Borodkin, V. S.; Kochetkov, N. K. Tetrahedron Lett.
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The reddish brown V2O5 solution obtained as described
above was added to a solution of tetrahydropyranyl
ether (1 mmol) in acetonitrile (3 mL). The resulting
solution was refluxed for 0.25 h. The solvent was
removed in vacuo and the residue redissolved in ethyl
acetate (20 mL). The organic layer was first washed
with 5% aq. sodium bicarbonate solution (5 mL), then
with water (5 mL) and finally dried over anhydrous
Na2SO4. The solvent was removed in vacuo and the
residue was purified by column chromatography (silica
gel, hexane:ethyl acetate) to afford the product.
5. Hosokawa, T.; Imada, Y.; Murahashi, S.-I. J. Chem.
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Acknowledgements
B.K.P. acknowledges the support of this research from
DST New Delhi and CSIR 01(1688)/00/EMR-II and
R.G. and A.P. acknowledge the financial support of the
Institute. Thanks are due to RSIC, Lucknow and
IACS, Kolkata for providing NMR and Mass spectra.
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