Efficient Aerobic Oxidation of Acetals to Esters Catalyzed by N-Hydroxy phthalimide (NHPI) and Co(II) under Mild Conditions

Article abstract of DOI:10.1055/s-2003-42396

Efficient oxidation of a variety of structurally diverse acetals, including open-chain acetals, 1,3-dioxanes, 1,3-dioxalanes, with molecular oxygen using catalytic amounts of N-hydroxyphthalimide (NHPI) in the presence of Co(OAc)₂ as co-catalyst was investigated.

Full text of DOI:10.1055/s-2003-42396

PAPER
2373
Efficient Aerobic Oxidation of Acetals to Esters Catalyzed by N-Hydroxy
phthalimide (NHPI) and Co(II) under Mild Conditions
Efficient
A
erobic
a
O
xidation
b
of
A
cetals to
a
Ester
s
k Karimi,* Jamshid Rajabi
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), P. O. Box 45195-159, Gava Zang, Zanjan, Iran
E-mail: karimi@iasbs.ac.ir
Received 24 March 2003; revised 21 July 2003
ation of alkynes to , -acetylenic ketones22 in the
Abstract: Efficient oxidation of a variety of structurally diverse ac-
presence of NHPI as key catalyst were reported. Recently
it has been shown that benzylidene acetals undergo oxida-
etals, including open-chain acetals, 1,3-dioxanes, 1,3-dioxalanes,
with molecular oxygen using catalytic amounts of N-hydroxy-
tive cleavage to give hydroxy mono-benzoate esters with
molecular oxygen in the presence of NHPI/MCPBA/
Co(OAc)2 in ethyl acetate at ambient temperature.23 Un-
fortunately, the scope of this method is limited to only a
few examples of benzylidene acetals. Moreover, in the
course of our studies, we found that this transformation
proceeded equally in both acetonitrile and ethylacetate
without the use of any added MCPBA. Therefore, we de-
cided to disclose our recent finding on the use of NHPI as
a catalyst for the direct aerobic oxidation of a variety of
structurally different acetals to the corresponding esters
(Scheme 1).
phthalimide (NHPI) in the presence of Co(OAc)2 as co-catalyst was
investigated.
Key words: esters, catalysis, oxidation
The protection of carbonyl compounds or diols as acetals
is of paramount importance in organic synthesis as shown
by a large number of methods that have been developed
for this key transformation.1 Moreover, direct oxidation of
both acetals and also aldehydes to the corresponding es-
ters is an interesting transformation in organic chemistry
as testified by a large number of reagents applied in this
reaction.2 This transformation was traditionally carried
out using stoichiometric amounts or Chromium salts,3
peracetic acid,4 DDQ,5 sodium perborate,6 halogen-based
reagents,7 Oxone,8 VO(OAc)2,9 etc. However, almost the
entirety of these protocols leads to expensive processes
and the formation of toxic by-products. Several other
methods, especially based on the use of inexpensive re-
agents such as H2O2, t-BuOOH were also developed for
OR1
OR1
Scheme 1
O
NHPI (cat.), Co(OAc)2 (cat.)
R
O2
R
OR1
CH3CN, r.t.
1 (atm)
We first examined the aerobic oxidation of (dimethoxym-
ethyl)benzene (1) as a model compound in the presence of
a catalytic amount of NHPI in CH3CN. The reaction of 1
in the presence of NHPI (10 mol%) under O2 (1 atm) for
20 hours afforded a trace amount of methyl benzoate (2)
at room temperature. When the similar reaction was car-
ried out using the same reagents and a catalytic amount of
Co(OAc)2 (0.5 mol%), 2 was formed with almost 70%
conversion. However, after optimization, the best ratios
for substrates, reagent and also reaction conditions were
found to be: 1 (1mmol), NHPI (20 mol%), Co(OAc)2 (1
mol%), O2 (1 atm) and room temperature, respectively.
Thus, we observed that under the above-optimized condi-
tions, 1 was completely converted into 2 giving 91% iso-
lated yield (Table 1, entry 1; Scheme 3, b).
this purpose, i.e. H2O2 and HCl,10 MTO–H2O2, t-
11
BuOOH/Pd(II),12 O3,13 and V2O5–H2O2.14 With rare ex-
ceptions, most of these protocols also suffer from draw-
backs such as use of excess of reagent, drastic conditions,
and tedious work-up. In many instances the methods af-
forded the corresponding esters in low yield. From both
environmental and economical point of views, the utiliza-
tion of molecular oxygen as final oxidant in oxidation pro-
cesses became increasingly attractive in recent years.
Unfortunately, despite the importance and attractiveness
of this opinion, less attention has been paid to the devel-
opment of new protocols for efficient oxidations of acetals
to the corresponding esters using molecular oxygen.15 It
has been shown by the elegant works of Ishii and co-
workers that the aerobic oxidation of various types of hy-
drocarbons using N-hydroxyphthalimide (NHPI) as a key
radical generator can be achived.16 Along this line, for ex-
ample, oxidation of alkyl benzenes at normal pressure of
O2 and ambient temperature,17 epoxidation of alkenes,18
selective oxidation of sulfides to sulfoxides,19 catalytic ni-
tration of alkenes,20 oxidation of alcohols,21 and oxygen-
Similarly, the aerobic oxidation of various types of substi-
tuted benzaldehyde dialkylacetals using the NHPI/Co(II)
system furnished the corresponding alkyl benzoates in
good to excellent yields (Table 1, entries 2–6). It is note-
worthy that the oxidation of cyclic acetals like 1,3-diox-
olanes or 1,3-dioxanes is of some interest because it
represents a route to selectively prepare the corresponding
diol monoesters. We found that the oxidation of a number
of aromatic 1,3-dioxolanes and 1,3-dioxanes as well as al-
iphatic counter parts afforded the corresponding diol
SYNTHESIS 2003, No. 15, pp 2373–2377
x
x.
x
x
.
2
0
0
3
Advanced online publication: 29.09.2003
DOI: 10.1055/s-2003-42396; Art ID: Z04203ss.pdf
© Georg Thieme Verlag Stuttgart · New York

2374
B. Karimi, J. Rajabi
PAPER
NHPI (20 mol%)
Co(OAc)2 (1 mol%)
O
O
O
O
O2
(1 atm)
Tol
Tol
No reaction
CH3CN, r.t., 30 h
Scheme 2 Tol = p-MeC6H4-
Scheme 3
monoesters in high yields (Table 1, entries 7–17). It is also N-oxyl radical (PINO) acts as the actual hydrogen-ab-
worth mentioning that no oxidation of the hydroxy group stracting species from C–H bonds through a free radical
on the resulting diol monoester took place at all. Surpris- chain.16,24 Therefore, similar to Minisci’s observation, we
ingly, we have observed that both pentaerythritol diacetals also believe that a polar transition state like 3 operates in
are thoroughly stable toward the reaction conditions even the second state of radical chains (Scheme 4).
after 30 h (Scheme 2). At this time we have not any expla-
It is well known that the interaction of Co(II) complexes
nation for the preservation of the acetal groups in pen-
with molecular oxygen generates the corresponding labile
taerythritol diacetal systems.
superoxocobalt(III) or -peroxocobalt(III) complexes, re-
Moreover, acid sensitive substrates such as aliphatic and spectively, via one-electron reduction of dioxygen
aromatic TBDMS ethers remain intact under these condi-
tions (Scheme 3, a).
Aromatic acetals bearing strong electron-withdrawing
groups such as 4-nitrophenyl survived under the described
reaction conditions (Table 1, entries 18, 19). Furthermore,
application of the present protocol to the oxidation of cy-
clic acetals derived from , -unsaturated systems was not
Equation 1
successful and a complex mixture of unidentified prod-
ucts was formed along with the desired diol monoesters
(Table 1, entry 20).
(Equation 1).25
Inspection of the data in Table 1 clearly shows that the ox-
These species presumably assist the generation of the
idation of acetals (especially aromatic acetals) is strongly
PINO radical from NHPI at room temperature.16 There-
governed by polar effects since electron-donating groups
fore, a plausible reaction pathway for aerobic oxidation of
accelerate the rate of the oxidation reaction and electron-
acetals using the NHPI/Co(II) system is outlined in
Scheme 5.
withdrawing groups act in the reverse manner. It has also
been shown previously that in situ generated phthalimid
In conclusion, we have demonstrated that the use of NHPI
combined with Co(OAc)2 is a catalytic system for the ef-
ficient and environmentally benign oxidation of a series of
open-chain as well as cyclic acetals with molecular oxy-
gen.
O
O
OR1
R CH(OR1)2
δ−
N O H
δ+
N O
C R
OR1
O
O
PINO
3
1H NMR and 13C NMR spectra were recorded on a Bruker 250 or
500 MHz spectrometer in CDCl3 as the solvent and TMS as internal
standard. All of the products are known and most of them are com-
mercially available and were identified through comparison of their
1H, 13C, and IR spectra with those of authentic samples.
O
OR1
OR1
N OH
R
O
NHPI
Scheme 4
Synthesis 2003, No. 15, 2373–2377 © Thieme Stuttgart · New York

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Efficient Aerobic Oxidation of Acetals to Esters
2375
O
O
N OH
O
R
OR1
O2
LnCo(III) O O
LnCo(II)
LnCo(III)
R1OH
OR1
OR1
R
LnCo(III) O OH
R1O OR1
OOH
PINO
NHPI
R
R1O OR1
OO
R
OR1
OR1
R
O2
Scheme 5
Table 1 Aerobic Oxidation of Acetals to Esters Using NHPI/Co(OAc)2 at Room Temperature
Entry
1
Substrate
Product
Time (h)
Yield (%)a,b
91
20
20
8
OMe
O
OMe
OEt
OMe
O
2
3
4
5
6
88
83
94
92
95
OEt
OEt
O
OEt
Cl
Br
Cl
Br
OEt
OEt
OEt
O
8
OEt
OEt
O
8
OEt
OEt
MeO
MeO
MeO
MeO
OEt
10
OEt
O
OEt
OEt
7
8
10
8
82
85
O
O
O
O
OH
O
O
O
O
Cl
Cl
OH
Synthesis 2003, No. 15, 2373–2377 © Thieme Stuttgart · New York

2376
B. Karimi, J. Rajabi
PAPER
Table 1 Aerobic Oxidation of Acetals to Esters Using NHPI/Co(OAc)2 at Room Temperature (continued)
Entry
9
Substrate
Product
Time (h)
8
Yield (%)a,b
88
O
O
O
O
MeO
MeO
OH
10
8
94
MeO
MeO
O
O
O
O
OH
11
12
13
14
12
5
84
89
92
89
O
O
O
O
OH
O
O
Cl
Cl
O
O
O
O
O
O
OH
OH
5
Br
Br
4
MeO
MeO
O
O
O
O
OH
15
8
91
O
O
O
O
MeO
MeO
OH
16
17
15
15
89
94
O
O
OH
O
O
O
O
O
OH
O
18
19
20
20
no reaction
no reaction
OEt
O
O2N
O2N
O2N
O2N
OEt
O
OEt
O
O
O
O
O
OH
20
20
34c,d
OH
O
O
a Isolated yields.
b The ratios of substrate:NHPI:Co(OAc)2 are 1:0.2:0.01.
c The reaction was completed within the indicated time; however, a mixture of unidentified products was formed.
d Yield as indicated from the NMR spectrum.
Aerobic Oxidation of Acetals to Esters Using a NHPI/Co(II)
System Under O2 (1 atm); General Procedure
sponding ester.
A solution of NHPI (2 mmol, 20 mol%) and Co(OAc)2·4H2O (0.1
mmol, 1 mol%) in CH3CN (25 mL) was prepared in a two-necked
flask. To this solution the acetal (10 mmol) was added and the re-
sulting pale yellow solution was stirred at r.t. under an oxygen at-
mosphere (1 atm, balloon filled) for the indicated optimized time
(Table 1). After completion of the reaction, the excess of solvent
was removed under reduced pressure; the products were purified by
chromatography through a short pad of silica gel to give the corre-
Spectroscopic Details of Selected Products
2-Hydroxyethyl 3-Methoxybenzoate (Table 1, entry 10)
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.57–7.58 (d, J = 7.7
Hz, 1 H), 7.50 (s, 1 H), 7.23–7.26 (t, J = 7.7 Hz, 1 H), 7.01–7.03 (dd,
J = 7.7, 2.7 Hz, 1 H), 3.75 (s, 3 H), 3.32 (br s, 1 H).
13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 166.89, 159.52,
131.19, 129.44, 122.07, 119.47, 114.31, 66.68, 60.92, 55.41.
Synthesis 2003, No. 15, 2373–2377 © Thieme Stuttgart · New York

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Efficient Aerobic Oxidation of Acetals to Esters
2377
3-Hydroxypropyl 4-Bromobenzoate (Table 1, entry 13)
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.78–7.80 (d, J = 7.4
Hz, 2 H), 7.47–7.49 (d, J = 7.4 Hz, 2 H), 4.38–4.40 (t, J = 6.1 Hz, 2
H), 3.70–3.72 (t, J = 6.1 Hz, 2 H), 3.13 (br s, 1 H), 1.92–1.97 (quin,
J = 6.1 Hz, 2 H).
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1351. (b) Pearson, R. G. J. Chem. Soc. 1960, 1682.
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13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 166.24, 131.67,
131.10, 129.01, 128.19, 62.29, 58.93, 31.75.
3-Hydroxypropyl 4-Methoxybenzoate (Table 1, entry 15)
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 7.96–7.98 (d, J = 8.9
Hz, 2 H), 6.89–6.91 (d, J = 8.9 Hz, 2 H), 4.43–4.45 (t, J = 6.2 Hz, 2
H), 3.84 (s, 3 H), 3.74–3.76 (t, J = 6.2 Hz, 2 H), 2.44 (br s, 1 H),
1.97–2.00 (q, J = 6.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3, 25 ºC, TMS): = 166.88, 163.51,
131.70, 122.51, 113.70, 61.58, 59.15, 55.49, 32.01.
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2-Hydroxyethyl Heptanoate (Table 1, entry 16)
1H NMR (500 MHz, CDCl3, 25 ºC, TMS): = 4.13–4.15 (m, 2 H),
3.74–3.76 (m, 2 H), 2.24–2.30 (t, J = 7.5 Hz, 2 H), 1.53–1.58 (m, 2
H), 1.37 (br s, 1 H), 1.24 (br m, 6 H), 0.81–0.84 (t, J = 7.0 Hz, 3 H).
(15) Kuramshin, E. M.; Gumerova, V. K.; Dyachenko, V. A.;
Kulak, L. G.; Molyavko, M. A.; Kochinashvili, M. V.;
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13C NMR(125 MHz, CDCl3, 25 ºC, TMS): = 173.56, 65.84, 61.98,
34.16, 31.43, 28.79, 24.83, 22.46, 13.97.
(16) Ishii, Y.; Sakaguchi, S.; Iwahama, T. Adv. Synth. Catal.
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Acknowledgment
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(18) Iwahama, T.; Sakaguchi, S.; Ishii, Y. Chem. Commun. 1999,
727.
The authors thank the Institute for Advanced Studies in Basic Sci-
ences (IASBS) Research Council for support of this work.
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1998, 39, 9059.
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Synthesis 2003, No. 15, 2373–2377 © Thieme Stuttgart · New York