Fe3O4 nanoparticles/ethyl acetoacetate system for the efficient catalytic oxidation of aldehydes to carboxylic acids

Article abstract of DOI:10.1016/j.tetlet.2014.02.133

A new methodology for the oxidation of aldehydes promoted by commercially available Fe₃O₄ nanoparticles (Fe₃O₄ NPs) activated by ethyl acetoacetate was developed. The use of ethyl acetoacetate as additive was crucial to achieve high reactivities. All reactions were realized under solvent free conditions, using air or tBuOOH as oxidants. Finally, the separation and reuse of the magnetically recoverable nanoparticles make this methodology very practical, simple and economical.

Full text of DOI:10.1016/j.tetlet.2014.02.133

Tetrahedron Letters 55 (2014) 2442–2445
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Fe O nanoparticles/ethyl acetoacetate system for the efficient
3
4
catalytic oxidation of aldehydes to carboxylic acids
Rosaria Villano , Maria Rosaria Acocella , Arrigo Scettri b
a,
⇑
b
a
Istituto di Chimica Biomolecolare—CNR, Trav. La Crucca 3, 07100 Sassari, Italy
Dipartimento di Chimica e Biologia—Università di Salerno, via Ponte Don Melillo, 84084 Fisciano (Salerno), Italy
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A new methodology for the oxidation of aldehydes promoted by commercially available Fe O4 nanopar-
3
Received 17 January 2014
Revised 19 February 2014
Accepted 28 February 2014
Available online 12 March 2014
3 4
ticles (Fe O NPs) activated by ethyl acetoacetate was developed. The use of ethyl acetoacetate as additive
was crucial to achieve high reactivities. All reactions were realized under solvent free conditions, using
air or tBuOOH as oxidants. Finally, the separation and reuse of the magnetically recoverable nanoparticles
make this methodology very practical, simple and economical.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Oxidation
Aldehydes
Carboxylic acids
Iron nanoparticles
Catalysis
Introduction
the end of the reaction by an external magnet and this opportunity
is particularly advantageous for the separation of a catalyst
In recent years, a great interest was paid to the development of
more sustainable synthetic strategies, as greener alternatives to old
characterized by much reduced particle size.
3 4
However, it has to be noted that the employment of Fe O NPs
1
traditional processes.
in oxidative processes has been poorly exploited in these last
2
11
The oxidation of aldehydes is a widely used reaction in organic
years.
chemistry, also for large scale applications. At present, some of
these procedures require very expensive and rare transition metal
In the course of an investigation targeted towards the achieve-
ment of new green protocols for the conversion of aldehydes into
carboxylic acids, promoted by nanocatalysts, we have found that
catalysts (ruthenium, palladium,4 copper,5 iridium,6 rhodium,
3
7
etc.) and the employment of solvents and so they are often charac-
terized by production of toxic metal waste at the end of the
reaction. All these aspects make many protocols environmentally
polluting and so their application in the chemical industry is often
difficult. Therefore, the possibility to realize alternative ‘green’
methodologies, also characterized by an easy separation and
recycle of the catalyst seems to be desirable.
3 4
the catalytic properties of Fe O NPs can be significantly increased
by performing the oxidation in the presence of 1,3-dicarbonyl
compounds, allowing the attainment of the final products with
satisfactory yields and selectivities. In this protocol, involving sol-
vent-free conditions, both air and tBuOOH were alternatively used
as oxidants. Finally, the possibility to magnetically recover and
3 4
reuse Fe O NPs without any significant reduction in efficiency
In this context, the application of magnetic iron oxide nanopar-
ticles (Fe O NPs) is a very promising area in the catalysis field.
3 4
makes this procedure very competitive because of its simplicity,
cheapness and environmental safety.
8
,9
The emerging interest for this kind of nanoparticles, which are
commercially available, is due to the possibility to modify their
properties by simple protocols, involving the formation of covalent
bonds with metal or organic ligands or, alternatively, simple
Results and discussion
In our study, p-anisaldehyde 1a and ethyl acetoacetate were
chosen respectively as the model substrate and the representative
10
coordination or adsorption of suitable activators. Notably, differ-
ent from other nanoparticles, Fe NPs can be easily recovered at
3 4
O
1
,3-dicarbonyl compound additive (Scheme 1).
However, a preliminary control experiment performed in the
⇑
Corresponding author. Tel.: +39 079 2841204; fax: +39 079 2841298.
E-mail address: rosaria.villano@icb.cnr.it (R. Villano).
absence of ethyl acetoacetate (Table 1, entry 1), pointed out the
very poor catalytic properties of Fe NPs. In fact, in the presence
3 4
O
http://dx.doi.org/10.1016/j.tetlet.2014.02.133
040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
0

R. Villano et al. / Tetrahedron Letters 55 (2014) 2442–2445
2443
O
O
H
Fe O NPs
3 4
OH
Ethyl acetoacetate
air
3
H CO
3
H CO
1
a
2a
Scheme 1. Oxidation of p-anisaldehyde.
of air as the oxidant and 20 mol % of Fe
found to take place at room temperature, while the final product
a could be isolated in only 8% yields after 24 h at 80 °C. Experi-
3 4
O NPs, no reaction was
2
Figure 1. Work-up: (a) mixture at the end of the reaction; (b) mixture after
ments in entries 2-4 revealed the beneficial effect of the presence
of ethyl acetoacetate, although the formation of 2a was found to
occur in rather modest yield (up to 42%). Notably, the increase of
air availability, as in entries 5 and 6, resulted in a more acceptable
efficiency (up to 62% yield).
Furthermore, an increase of catalyst up to 40 mol % did not re-
sult in a significant improvement of the process (entries 7 and 8),
as well as the use of an excess of ethyl acetoacetate (entry 10).
On the other hand, the structure of the employed 1,3-dicarbonyl
compound seemed to influence notably the preparative outcome,
as confirmed in entry 11 where methyl acetoacetate was used un-
der the optimized conditions (compare entries 6 and 11). Of
course, product 2a was isolated in only low yield by performing
addition of EtOAc; (c) easy magnetic separation of the catalyst.
O
O
H
Fe O NPs
3 4
OH
Ethyl acetoacetate
3
H CO
H CO
3
(
1 equiv)
1
a
2a
Scheme 2. Model reaction.
Table 2
Oxidant screening for the oxidation of p-anisaldehyde 1a
2a Yielda (%)
the oxidation in the absence of Fe
3
O
4
NPs (entry 12) or in the
Entry
Fe O NPs (%)
Oxidant
t (h)/T (°C)
3
4
presence of a catalytic amount of ethyl acetoacetate (entry 13).
Moreover, the background oxidation of aldehyde 1a after 24 h at
1
2
3
4
5
6
20
Air (1 atm)
24/80
1/80
4/80
24/80
24/80
24/80
62
55
72
84
27
20
b
20
20
20
—
tBuOOH (1 equiv)
tBuOOHb (1 equiv)
8
3 4
0 °C, in the absence of Fe O NPs and ethyl acetoacetate, was very
tBuOOHb (1 equiv)
modest (entry 14).
b
tBuOOH (1 equiv)
Finally, scale-up experiments were realized to evaluate the
applicability of the optimized conditions of entry 6: in these cases,
the model aldehyde (0.625 mmol and 1.0 mmol) reacted without a
significant reduction in efficiency (59% and 61% isolated yields
respectively).
c
20
H
2
O
2
(1 equiv)
a
b
c
Isolated yields.
5
3
.5 M solution in decane.
0% hydrogen peroxide solution.
At the end of each experiment, a very viscous mixture was ob-
served (Fig. 1a). So, in order to make an easy magnetic separation
of the catalyst, a small amount of ethyl acetate (1.0 ml) was added
during work-up (Fig. 1b) and the nanoparticles were recovered by
using an external magnet (Fig. 1c).
because in the oxidation of aldehydes with tBuOOH catalyzed by
1
2
13
5b
Bi
2
O
3
, Mohr’s salt or CuBr
2
an excess of oxidant (up to
5 equiv) and the presence of solvent were required in order to have
good conversions. On the contrary, in this case, when a stoichiom-
etric amount of tBuOOH was used as the oxidant, the correspond-
ing acid 2a was obtained in 72% isolated yield after only 4 h
(Table 2, entry 3) and 84% after 24 h (entry 4). Moreover, a control
experiment performed in the absence of iron nanoparticles
Then, the performance of other oxidants was investigated
(Scheme 2, Table 2). Model aldehyde 1a could be smoothly trans-
formed into the desired carboxylic acid 2a by using a stoichiome-
tric amount of tBuOOH. This result was particularly intriguing
Table 1
Optimization of reaction conditions for the oxidation of p-anisaldehyde 1a
Entrya
Fe
NPs (%)
Ethyl acetoacetate (equiv)
t (h)/T (°C)
2a Yieldb (%)
3
O
4
1
2
3
4
20
20
20
20
20
20
40
40
10
20
20
—
—
1
1
1
1
1
1
1
1
2
1
1
0.20
—
24/80
1/80
8
15
35
42
49
62
28
39
46
63
43
19
23
19
24/80
48/80
24/80
24/80
24/80
24/80
24/80
24/80
24/80
24/80
24/80
24/80
c
5
d
6
7
d
8
9
d
1
1
1
1
1
0d
d,e
1
2
3
4
d
d
d
20
—
a
All reactions were carried out under solvent-free conditions in a closed vial (size 4 ml) with 0.0625 mmol of aldehyde at 80 °C (oil bath) for the indicated time, using air
(
1 atm) as the oxidant. The carboxylic acid 2a was the exclusive product.
b
Yields refer to isolated compounds 2a.
In this entry the reaction was performed in a closed vial (size 15 ml).
The reaction was realized in an open system.
c
d
e
The reaction was realized in the presence of methyl acetoacetate instead of ethyl acetoacetate.

2
444
R. Villano et al. / Tetrahedron Letters 55 (2014) 2442–2445
O
O
O
Fe O NPs (20%)
O
3
4
R
H
R
OH
H
Fe O NPs
3 4
Ethyl acetoacetate (1equiv),
Oxid., 24h/80°C
OH
1
2
Ethyl acetoacetate (1equiv),
air, 24h/80°C
3
H CO
H CO
3
1
a
2
a
Scheme 3. Application of the methodology to different aldehydes.
Scheme 4. Model reaction.
confirmed their determining role for a successful oxidative process
even though, in this last case, no negligible yield was observed (en-
Table 4
Recycling of the Fe O4 NPs
3
2 2
try 5). Furthermore, H O was less efficient than tBuOOH (entry 6).
Entry
Cycle
Yielda (%)
The success of this methodology was further demonstrated by
applying the optimized conditions (air or tBuOOH as the oxidant)
to different aldehydes (Scheme 3).
1
2
3
4
1
2
3
4
62
66
59
61
As shown in Table 3, our experiments revealed that Fe
ethyl acetoacetate was able to catalyze the oxidation of different
classes of aldehydes (aromatic, aliphatic and ,b-unsaturated).
3 4
O NPs/
a
Isolated yields.
a
Moreover, for aromatic aldehydes, both substrates bearing either
electron-withdrawing or electron-donating groups reacted well
at 80 °C, except for nitro-derivatives: in these cases, modest (entry
Conclusions
In this Letter we propose a competitive methodology for the
oxidation of aldehydes to carboxylic acids, catalyzed by commer-
cially available Fe O nanoparticles activated by ethyl acetoacetate.
3 4
The catalytic system was able to promote the reaction by using
tBuOOH as the oxidant as well as by using air. This last alternative
makes this strategy particularly intriguing; moreover, other advan-
tages such as the solvent-free approach and the possibility to
recover easily (by an external magnetic field) and reuse the iron
oxide nanoparticles are very important from the view point of
6
) or poor (entry 7) yields were observed. Good results were
observed also with low molecular weight aldehydes (entries 11
and 13), by performing the reaction in a closed vial (size 15 ml).
3 4
On the other hand, the same catalytic system Fe O NPs/ethyl
acetoacetate was also tested in the oxidation of benzyl alcohol,
but no oxidation product was observed so that starting material
could be recovered completely unchanged. This result confirms
that the methodology is suitable for the selective oxidation of
aldehydes to carboxylic acids.
‘
green chemistry’.
Finally, the reusability of the nanoparticles was examined in the
model reaction (Scheme 4). Even though the catalyst loading
seems to be quite high (20 mol %), it could be recovered easily
and reused. In fact after the reaction, the metal catalyst was recov-
ered magnetically (as shown in Fig. 1), washed with EtOAc and
dried in vacuum at 80 °C for 2 h. Afterwards, a new reaction was
performed by adding aldehyde and ethyl acetoacetate under the
optimized conditions. The results in Table 4 showed that the nano-
particles could be used at least four times without a significant
change in activity.
Experimental
General
TLC was performed on Merck Kiesegel 60 F254 plates and visual-
ized by a 254 nm UV lamp. Column chromatographic purification
of products was carried out using silica gel 60 (70–230 mesh,
Merck). All reagents (Aldrich and Fluka) were used without further
purification. Fe
3 4
O NPs were purchased from Sigma–Aldrich. NMR
1
spectra were recorded on a Varian 400 (400.135 MHz for H and
1
3
1
00.03 MHz for C) spectrometer.
Table 3
Application of the methodology to different aldehydes 1
Typical procedure for the oxidation of aldehydes to carboxylic
acids
Entry
1
Aldehyde 1
Oxid.a
Prod.
2 Yieldb (%)
4-Methoxybenzaldehyde (1a)
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
A
B
A
A
A
A
2a
2a
2b
2b
2c
2c
2d
2d
2e
2e
2f
62
84
85
91
85
80
71
99
26
67
23
45
ND
ND
99
54
33
63
87
30
80
To a vial with the catalyst (20 mol %) under air, aldehyde
(
0.0625 mmol) and ethyl acetoacetate (1 equiv) were added. The
2
3
4
5
6
7
Biphenyl-4-carboxaldehyde (1b)
4-Cyanobenzaldehyde (1c)
4-Methylbenzaldehyde (1d)
2-Fluorobenzaldehyde (1e)
4-Nitrobenzaldehyde (1f)
2-Nitrobenzaldehyde (1g)
mixture was heated at 75–80 °C for 24 h. After cooling at rt, ethyl
acetate (1.0 ml) was added and the catalyst was separated by sim-
ple magnetic decantation. Then, the combined solvent was re-
moved in vacuo and the mixture was purified via trituration or
flash column. Spectroscopic data of products 2 were consistent
1
4
15
16
14
17
with those reported in the literature (2a, 2b, 2c, 2d, 2e,
14
18
19
20
21
2
f, 2h, 2i, 2j and 2k ).
-Methoxybenzoic acid (2a):
3
400 MHz, CDCl ) d 8.06 (d, 2H, J = 8.8 Hz), 6.95 (d, 2H, J = 8.8 Hz),
2f
14
5.9 mg, 62% yield. 1H NMR
4
2g
2g
2h
2i
2i
2j
2j
2k
2k
(
1
3
8
9
Dodecanal (1h)
trans-Cinnamaldehyde (1i)
3.88 (s, 3H). C NMR (100 MHz, CDCl
3
) d 171.4, 164.0, 132.3,
121.6, 113.7, 55.5.
Biphenyl-4-carboxylic acid (2b):15 10.5 mg, 85% yield. 1H NMR
10
11
12
13
trans-2-Hexen-1-al (1j)
trans-2-Hexen-1-al (1j)
2-Methylpentanal (1k)
2-Methylpentanal (1k)
c
c
(400 MHz, CDCl
.63 (m, 2H), 7.50–7.39 (m, 3H). C NMR (100 MHz, CDCl
170.6, 146.5, 139.9, 130.7, 129.0, 128.3, 127.5, 127.3, 127.2.
3
) d 8.20–8.18 (m, 2H), 7.72–7.69 (m, 2H), 7.66–
1
3
7
3
) d
1
6
1
a
b
c
4-Cyanobenzoic acid (2c):
7.8 mg, 85% yield.
H
NMR
Oxidant A: air; oxidant B: tBuOOH.
Isolated yields.
(400 MHz, CDCl ) d 8.20 (d, 2H, J = 8.4 Hz), 7.79 (d, 2H, J = 8.4 Hz).
3
13
In this entry the reaction was performed in a closed vial (size 15 ml) and the
Cl instead of EtOAc.
C NMR (100 MHz, CDCl
3
) d 169.2, 132.9, 132.3, 130.7, 117.8,
metal catalyst was washed with CH
2
2
1
17.2.

R. Villano et al. / Tetrahedron Letters 55 (2014) 2442–2445
2445
4
-Methylbenzoic acid (2d):14 6.0 mg, 71% yield. 1H NMR
400 MHz, CDCl ) d 7.99 (d, 2H, J = 8.0 Hz), 7.27 (d, 2H, J = 8.0 Hz),
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(
3
3
1
2
.43 (s, 3H). C NMR (100 MHz, CDCl
29.2, 126.5, 21.8.
3
) d 172.3, 144.7, 130.3,
2
3
.
.
1
-Fluorobenzoic acid (2e):17 2.3 mg, 26% yield. 1H NMR
2
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(
3
400 MHz, CDCl ) d 8.06–8.01 (m, 1H), 7.62–7.56 (m, 1H), 7.26–
.15 (m, 2H). C NMR (100 MHz, CDCl ) d 168.8, 161.3, 135.5 (d,
3
4319–4327.
1
3
7
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-Nitrobenzoic acid (2f):14 2.4 mg, 23% yield. H NMR (400 MHz,
1
4
1
3
CDCl
100 MHz, CDCl
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) d 8.33 (d, 2H, J = 8.8 Hz), 8.28 (d, 2H, J = 8.8 Hz). C NMR
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(
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Dodecanoic acid (2h): 12.4 mg, 99% yield. 1H NMR (400 MHz,
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6H), 0.89 (t, 3H, J = 6.7 Hz). C NMR (100 MHz, CDCl ) d 179.7,
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.30 (m, 3H), 1.18 (d, 3H, J = 7.2 Hz), 0.92 (t, 3H, J = 7.2 Hz).
3
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3
NMR (100 MHz, CDCl ) d 182.5, 39.0, 35.6, 20.3, 16.8, 13.9.
5
1
Acknowledgment
5
We are grateful to MIUR and University of Salerno for financial
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References and notes
1
.
(a)Green Chemistry and Catalysis; Sheldon, R. A., Arends, I., Hanefeld, U., Eds.;
Wiley-VCH Verlag GmbH & Co. KgaA: Weinheim, 2007; (b)Methods and