Oxone: A convenient reagent for the oxidation of acetals

Article abstract of DOI:10.1055/s-1999-2703

Symmetrical cyclic and acyclic acetals by oxidation with Oxone gave the corresponding esters in good yield. Treatment of tetrahydropyranyl derivatives of alcohols with the same reagent resulted in oxidative regeneration of the alcohols.

Full text of DOI:10.1055/s-1999-2703

LETTER
777
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Oxone : A Convenient Reagent for the Oxidation of Acetals
*
Massimo Curini, Francesco Epifano, Maria Carla Marcotullio, Ornelio Rosati
Istituto di Chimica Organica, Facoltà di Farmacia, Università di Perugia, Via del Liceo, I-06123 Perugia, Italy
Fax +39-75-5855116; E-mail: Cecchere@unipg.it
Received 4 February 1999
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Table 1. Oxidation of acetals by Oxone on wet Al O
2
3
Abstract: Symmetrical cyclic and acyclic acetals by oxidation with
®
Oxone gave the corresponding esters in good yield. Treatment of
tetrahydropyranyl derivatives of alcohols with the same reagent re-
sulted in oxidative regeneration of the alcohols.
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Key words: Oxone , acetal oxidation, tetrahydropyranyl ether
cleavage, glycol monoester formation
Cyclic acetals find wide application in organic synthesis
1
particularly as protecting groups of aldehydes, and they
can be used for the preparation of hydroxyalkyl carboxy-
lates which are commercially important products.2
In recent years several oxidising agents have been used
for the conversion of cyclic and acyclic acetals into esters,
3
4
such as ozone, molecular oxygen, potassium permanga-
5
6
7
nate, t-butyl hydroperoxide, halogen-based reagents,
and sodium perborate. Unfortunately, many of these pro-
cedures suffer limitations such as difficulty of handling.
8
Recently we reported that potassium hydrogen persulfate,

which is commercially available as Oxone , can be used
for a large number of transformations, i.e. the oxidation of
9
selenides to selenones, the carbonyl regeneration from
1
0
1
,3-dithianes and dithiolanes, and the oxidative Nef re-
1
1
action.
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Based on the versatility of Oxone as oxidant and on the
1
0
carbonyl regeneration from thioacetals, we decided to
test Oxone ® on cyclic acetals (Scheme 1).
Scheme 1
While optimizing the reaction conditions of acetal oxida-
tion, we found that treatment of 1,3-dioxolanes and 1,3-
®
12
dioxanes with Oxone supported on wet alumina, in
chloroform at 50 °C, afforded in 2-10 h hydroxy esters in
1
3
good yields (Table 1).
a
1
4
Yields in pure isolated products, characterized by IR, GC-MS, H
Unlike other procedures acyclic acetals reacted with
equal ease as cyclic acetals. 1,3-Dioxolanes and 1,3-diox-
anes gave the corresponding esters in good yields. This re-
action represents a new methodology for the conversion
of aldehydes into esters.
1
3
b
c
NMR and C NMR. 20% of aldehyde was recovered. 10% of alde-
hyde was recovered. 19% of aldehyde was recovered.
d
terest is due to the possibility that compound a, in princi-
All the acetals studied were symmetrical and we thought ple, could decompose in two different ways, giving
it interesting to test the oxidation of unsymmetrical acetals hydroxy ester b or lactone c plus the alcohol d. (Scheme
such as tetrahydropyranyl derivatives of alcohols. This in- 2)
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78
M. Curini et al.
LETTER
changed the solvent from methanol to dioxane, running
the reaction at 80 °C. Using these new conditions we were
able to increase the alcohol amount and decrease the ester
formation (Table 3).
Scheme 2
Table 3. Tetrahydropyranyl ethers decomposition in dioxane in the
®
presence of Oxone .
It has been reported that THP ethers treated with ozone or
perborate gave rise exclusively to the formation of the hy-
3
,8,14
droxy esters,
while treatment with other oxidants led
1
5
to oxidative deprotection. We found that tetrahydropyr-
anyl ethers of several alcohols react easily with Oxone®
under the same reaction conditions as acetals to give
mainly alcohol d together with a small amount of ester b
in poor overall yields. The same reaction when run in
®
methanol using 2 equivalents of Oxone gave better over-
all yields, but still no chemoselectivity (Table 2).16
Table 2. Tetrahydropyranyl ethers decomposition in MeOH in the
®
presence of Oxone .
a
1
Yields in pure isolated products, characterized by IR, GC-MS, H
1
3
NMR and C NMR.
Neither the use of acetal oxidation nor THP ether cleavage
conditions allowed us to oxidise ketals. This led us to
think that the first step in the oxidation process is the in-
®
sertion of Oxone into the C-H bond of acetal 1 forming
an orthoester 2 which then decomposes leading to ester 3
and/or alcohol 4.
Scheme 3
In conclusion the present method represents a simple, rap-
id way to oxidise symmetrical acetals to esters and to
deprotect tetrahydropyranyl ethers. The reagent is cheap,
non-toxic and the inorganic salts are removed easily.
a
1
Yields in pure isolated products, characterized by IR, GC-MS, H
NMR and 13C NMR. b 22% of 5-nonanone was recovered.
Acknowledgement
The authors wish to thank MURST “Progetto Chimica dei Compo-
sti Organici di interesse biologico” and CNR (Rome) for financial
support.
It is known that simple heating of hydroxy ester b produc-
es δ-valerolactone c and alcohol d. With this in mind we
3
Synlett 1999, No. 6, 777–779 ISSN 0936-5214 © Thieme Stuttgart · New York

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LETTER
Oxone : A Convenient Reagent for the Oxidation of Acetals
779
References and Notes
(12) Greenhalgh, R. P. Synlett 1992, 235.
(
13) A typical procedure is as follows. To a stirred solution of the
(
(
(
(
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12
acetal (1 mmol) in 10 ml of CHCl , 3 g of wet Al O and
3
2
3
®
Oxone (3 mmol) were added. The resulting suspension was
stirred at 50 °C until no more starting material was detected by
TLC and GC-MS. The mixture was then cooled and filtered
with a sintered-glass funnel. The residue was washed with
CHCl and the combined organic layers were concentrated.
3
The crude material was purified by SiO column
chromatography (eluent: 5% methanol in CH Cl ).
2
2
2
(
(
(
14) For theoretical considerations about the formation of the
hydroxyester see ref. 3.
(
(
15) Raina, S.; Singh, V. K. Synth. Commun. 1995, 2395. Datta-
Gupta, A.; Singh, R.; Singh, V. K. Synlett 1996, 69.
16) A typical procedure is as follows. To a stirred solution of the
12
acetal (1 mmol) in 10 ml of MeOH, 3 g of wet Al O and
2
3
®
Oxone (3 mmol) were added. The resulting suspension was
stirred at 50 °C until no more starting material was detected by
TLC and GC-MS. The mixture was then cooled and filtered
with a sintered-glass funnel. The residue was washed with
(
7) Prugh, J. D.; McCarthy, W. C. Tetrahedron Lett. 1966, 1351.
Pearson, R. G. J. Chem. Soc., 1960, 1682. Wright, J. B. J. Am.
Chem. Soc. 1955, 77, 4883.
CHCl and the combined organic layers were concentrated.
3
(8) Bhat, S.; Ramesha, A. R.; Chandrasekaran, S. Synlett 1995,
The crude material was purified by SiO column
chromatography (eluent: 5% methanol in CH Cl ).
2
329.
2
2
(
9) Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.;
Rosati, O. J. Org. Chem. 1995, 60, 8412.
(
(
10) Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.;
Rosati, O. Synlett 1996, 767.
11) Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.;
Rosati, O. Synth. Commun. 1998, 3057.
Article Identifier:
1
437-2096,E;1999,0,06,0777,0779,ftx,en;G06199ST.pdf
Synlett 1999, No. 6, 777–779 ISSN 0936-5214 © Thieme Stuttgart · New York