Heterogeneous Baeyer-Villiger oxidation of ketones with H2O2/nitrile, using Mg/Al hydrotalcite as catalyst

Article abstract of DOI:10.1016/j.tet.2006.11.081

We synthesized a magnesium-aluminium hydrotalcite and used it as a catalyst in the Baeyer-Villiger (BV) oxidation of cyclohexanone with a mixture of 30% aqueous hydrogen peroxide and benzonitrile as oxidant. The hydrotalcite proved an excellent catalyst for the process. The influence of experimental variables was examined in depth in order to bring the working conditions as close as possible to those usable on an industrial scale. We optimized the cyclohexanone/hydrogen peroxide/benzonitrile proportion and used various nitriles, solvents and amounts of catalyst, benzonitrile and methanol proving the most effective nitrile and solvent, respectively, for the intended purpose. The reaction was found to occur to an acceptable extent with other carbonyl compounds as substrates; by exception, α,β-unsaturated carbonyl compounds provided poor results by effect of their undergoing competitive epoxidation of their double bonds.

Full text of DOI:10.1016/j.tet.2006.11.081

Tetrahedron 63 (2007) 1435–1439
Heterogeneous Baeyer–Villiger oxidation of ketones with
H O /nitrile, using Mg/Al hydrotalcite as catalyst
2
2
*
*
Rafael Llamas, C ꢀe sar Jim ꢀe nez-Sanchidri ꢀa n and Jos ꢀe Rafael Ruiz
Departamento de Qu ꢀı mica Org aꢀ nica, Universidad de C oꢀ rdoba, Campus de Rabanales, Edificio Marie Curie,
Carretera Nacional IV-A, km. 396, 14014 C oꢀ rdoba, Spain
Received 31 October 2006; revised 21 November 2006; accepted 24 November 2006
Available online 19 December 2006
Abstract—We synthesized a magnesium–aluminium hydrotalcite and used it as a catalyst in the Baeyer–Villiger (BV) oxidation of cyclo-
hexanone with a mixture of 30% aqueous hydrogen peroxide and benzonitrile as oxidant. The hydrotalcite proved an excellent catalyst for
the process. The influence of experimental variables was examined in depth in order to bring the working conditions as close as possible
to those usable on an industrial scale. We optimized the cyclohexanone/hydrogen peroxide/benzonitrile proportion and used various nitriles,
solvents and amounts of catalyst, benzonitrile and methanol proving the most effective nitrile and solvent, respectively, for the intended
purpose. The reaction was found to occur to an acceptable extent with other carbonyl compounds as substrates; by exception, a,b-unsaturated
carbonyl compounds provided poor results by effect of their undergoing competitive epoxidation of their double bonds.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
The use of heterogeneous catalysts in oxidation processes
has been dramatically revolutionized by the discovery of
Ti-silicalite (TS-1). This solid consists of a zeolite structure
6
The oxidation of cyclic and linear ketones to their respective
lactones and esters with oxidants such as organic peroxides
or peroxyoxides, alkyl hydroperoxides or hydrogen peroxide
(silicalite) into which titanium is incorporated. It possesses
a high oxidizing power, which lies in the ability of titanium
metal sites to form Ti-peroxide species that can activate
hydrogen peroxide in various oxidation reactions including
1
is known as the Baeyer–Villiger (BV) reaction. The BV
reaction also includes the oxidation of aldehydes to formate
esters. The currently accepted general mechanism for this
reaction with organic peroxides involves two steps (see
Scheme 1), namely, addition of the peroxyacid to the
carbonyl compound to form a Criegee adduct (1) and rear-
7
,8
epoxidation, ammonoxidation and CH oxidation.
The
original catalyst has been refined by inserting other oxidiz-
ing metals into the zeolite structure, albeit with poorer
results than those obtained with titanium. Corma et al. devel-
oped a catalyst consisting of Sn incorporated into a beta
2
rangement of the adduct to the reaction end-product (2),
which retains the stereochemistry of the migrating site.
3
9
10–15
zeolite. In subsequent work,
Corma and co-workers
The BV reaction requires the presence of a catalyst to occur;
such a catalyst can be of the acid–base or enzyme type and is
usually employed in a homogeneous phase with the reaction
conducted extensive research into Baeyer–Villiger oxidation
reactions using their Sn–beta zeolite catalysts. Recently,
they proposed a mechanism for the underlying process
from a combination of theoretical and experimental data;
based on it, tin, which acts as an oxygen transfer agent,
activates the carbonyl group in the ketone.
4
,5
16
ingredients.
The oxidants used are almost invariably
organic peroxides, which can produce large amounts of
environmentally hazardous by-products. The environmental
concern they have raised and the advantages of heteroge-
neous catalysts over homogeneous catalysis have propitiated
the development of effective heterogeneous catalysts for the
BV oxidation with hydrogen peroxide in recent years.
Hydrogen peroxide as an oxidant has some advantages
such as its ease of use, the large amount of active oxygen
it can supply and the decreased production of the sole
by-product it generates (water).
Various other catalysts have been successfully used in BV
oxidation reactions. Some are based on hydrotalcite-like
structures that are used in combination with other oxidants
1
7–19
20
such as benzaldehyde/O mixtures
or peroxyacids.
Also, a hydrotalcite-supported SnO catalyst was found to
2
2
2
1
effect BV oxidations with hydrogen peroxide in the pres-
ence of a nitrile as oxygen transfer reagent. Hydrotalcites
constitute a family of natural or synthetic materials, also
named layered double hydroxides (LDH), the structure of
which derives from hydrotalcite [a magnesium–aluminium
hydroxycarbonate of formula MgAl (OH) CO $4H O
Keywords: Hydrotalcite; LDH; Baeyer–Villiger oxidation; Nitrile.
*
2
4
Corresponding authors. Tel.: +34 957 218638; fax: +34 957 212066;
e-mail: qo1ruarj@uco.es
2
16
3
2
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.081

1436
R. Llamas et al. / Tetrahedron 63 (2007) 1435–1439
B-
H+
O
O
H
O
R´´
R´´CO H
O
HB
2
3
R´
1
R
R
R´
O
O
R
O
R´
(1)
(2)
Scheme 1. General mechanism for the Baeyer–Villiger oxidation of ketones with organic peracids.
2
+
structurally similar to brucite where some Mg ions are re-
2. Results and discussion
3
+
placed with Al ions in such a way that positively charged
layers are formed and their charge neutralized by carbonate
ions in the interlayer region]. The structure of hydrotalcite
is compatible with variable Mg/Al ratios and also with the
exchange of metal cations and anions; this has facilitated
2
2,23
In previous work,
we found hydrotalcites to be effective
catalysts for the BVoxidation of cyclic ketones with hydro-
gen peroxide/benzonitrile mixtures in a large excess with
respect to the carbonyl compound. Also, we found the re-
action rate to be substantially increased by the addition of
a surfactant such as sodium dodecylsulfate. As noted in
Section 1, we proposed a mechanism for the reaction based
on the results.
the production of a large family of hydrotalcite-like mate-
rials of general formula [M(II)1 M(III) (OH) ] (A
x+ nꢀ
)
ꢀx
x
2
A$mH O, with x¼M(III)/[M(II)+M(III)].
2
22,23
In previous work,
we used hydrotalcites as effective
catalysts for the BVoxidation of cyclohexanone with hydro-
gen peroxide. Also, we examined the influence of the nature
of the catalyst on its activity and proposed a mechanism
involving two steps, namely (1) the initial attack of hydrogen
peroxide on a Bronsted basic site at the catalyst surface to
form a hydroperoxide species, followed by the attack of
such a species on benzonitrile to give a peroxycarbox-
imidic acid intermediate and (2) the attack of the previous
intermediate on cyclohexanone adsorbed at an acid site
of the catalyst to form an intermediate equivalent to the
Criegee adduct in homogeneous catalysis processes that
undergoes rearrangement to 3-caprolactone, the peroxycar-
boximidic intermediate being transformed into benzamide
We subsequently set to optimize the process with a view to
its transfer to a more ‘realistic’ operating scale. We used
cyclohexanone as substrate in all tests in order to reduce
the amount of benzonitrile and hydrogen peroxide needed,
and also that of catalyst. To this end, we used variable
benzonitrile/cyclohexanone and hydrogen peroxide/cyclo-
hexanone ratios in order to bring the operating conditions
closer to the industrial case and render the process feasible.
This additionally involved performing some tests with vari-
able amounts of catalyst that revealed 0.1 g to be appropriate
for our purpose. The optimum benzonitrile/cyclohexanone
ratio was found to be 4. In order to ensure that the reaction
would not be affected by the volume loss resulting from a de-
creased nitrile/ketone ratio, the reaction vessel was filled
with methanol to the volume used in the previous tests.
Then, the optimum amount of hydrogen peroxide was deter-
mined under the new conditions. As before, the reaction
vessel was filled with water as the hydrogen peroxide/cyclo-
hexanone ratio was lowered in order to ensure that the final
volume coincided with that used until then. Based on the
results obtained with variable hydrogen peroxide/cyclo-
hexanone ratios, an amount of 2 equiv of hydrogen peroxide
proved optimal.
(
see Scheme 2).
In this work, we expanded the above-described study by
examining the influence of some experimental variables
including the solvent, nature of the nitrile and amount of
catalyst with a view to bringing them as close to those used
in large-scale work as possible. All tests were conducted by
using an Mg/Al hydrotalcite with a metal ratio of 4, which
was previously found to be the best choice for the intended
2
2
purpose.
δ+
δ−
OH
M
NH
O
δ+
O
OH
M
H O
2
2
OH
-
NH2
O
N
+
O
O
M
O
2 2
Scheme 2. Mechanism for the Baeyer–Villiger oxidation of cyclohexanone with H O over HT as catalyst.

R. Llamas et al. / Tetrahedron 63 (2007) 1435–1439
1437
As noted earlier, the reaction medium was supplied with an
amount of methanol identical with that by which the volume
of benzonitrile used was reduced in order to ensure con-
stancy in the total volume of the reaction medium in all tests.
We then examined the influence of variably polar solvents on
the reaction. As can be seen from Table 1, the best conver-
sion values were obtained with methanol, the other three
solvents performing more or less similarly in this respect.
This is consistent with the proposed mechanism, based on
which the reaction takes place at the interface between the
organic and aqueous phases in the reaction medium, so the
presence of a surfactant must increase the contact area
between the two phases and favour the reaction—as was
indeed the case. A solvent such as methanol, which can
further increase the contact area between the two phases as
it is miscible with both, therefore provided better results
than other, water-immiscible solvents, as reflected in the
experimental results. Because the other three solvents were
immiscible with water, their results should be relatively
similar—as they actually were in practice.
based on an Mg/Al layered double hydroxide or metal
hydroxide.
2
4,25
This can be ascribed to the formation of
carbanionic species through the loss of acid protons from
the a carbon of the nitrile by effect of the basic character
of the catalyst, which decreased the final conversion. In
order to check whether this effect was also present in our
reaction, we conducted it in the presence of various nitriles
with and without a protons. Table 2 shows the results. As
with the epoxidation of limonene, the use of a nitrile with
Table 3. Conversion and selectivity obtained in the Baeyer–Villiger oxida-
tion of various ketones with hydrogen peroxide over Mg/Al hydrotalcite
as catalyst
a
b
Conversion (%) Selectivity (%)
c
Entry Substrate
Product
O
O
O
1
2
100
100
100
90
O
O
O
O
O
O
O
Table 1. Influence of the solvent on the Baeyer–Villiger oxidation of cyclo-
hexanone with hydrotalcite as catalyst
a
3
4
5
6
100
100
100
100
54
100
100
100
b
Entry
Solvent
Conversion (%)
O
O
1
2
3
4
5
6
Benzonitrile
Toluene
Dioxane
1-Butanol
Methanolc
Methanol
100
65 (85)
53 (86)
58 (78)
73 (96)
0
O
O
a
Reaction conditions: cyclohexanone: 12 mmol; benzonitrile: 48 mmol;
hydrogen peroxide: 2 equiv (30% v/v aqueous solution); catalyst: 0.1 g;
O
ꢁ
T¼70 C; surfactant (DBS): 0.6 mmol.
b
c
Conversion to 3-caprolactone after 6 h (in brackets conversion after 24 h).
Reaction without benzonitrile.
O
O
O
O
O
O
While the primary aim of this work was to render the reac-
tion feasible for 3-caprolactone production in a large scale,
it would be more economical to use acetonitrile instead of
benzonitrile. We therefore examined the influence of using
acetonitrile and other nitriles, with and without acid protons
in a-position with respect to the nitrile group, as co-oxidants
on the BV oxidation of cyclohexanone. The epoxidation of
7
64
32
O
O
O
O
O
8
9
70
71
26
29
2
4,25
limonene with hydrogen peroxide and benzonitrile
takes
O
place via a mechanism similar to that for the BVoxidation in
the first step (both involve the formation of a peroxycarb-
oximidic intermediate that acts as the actual oxidant). The
epoxidation of limonene was found to provide better results
in the presence of a nitrile with no acid protons in a-position
than that of a nitrile possessing such protons or a catalyst
O
1
1
0
1
2
70
96
100
100
100
N
N
O
O
O
O
O
O
Table 2. Conversion to 3-caprolactone in the Baeyer–Villiger oxidation of
cyclohexanone over HT–Mg/Al with hydrogen peroxide and different
nitriles as oxidants
O
O
N
N
a
N
N
b
Entry
Nitrile
Conversion (%)
1
2
3
4
Acetonitrile
28 (57)
43 (63)
51 (74)
73 (99)
1
100
Phenylacetonitrile
Acrylonitrile
Benzonitrile
a
Reaction conditions: ketone: 12 mmol; benzonitrile: 48 mmol; hydrogen
ꢁ
a
Reaction conditions: cyclohexanone: 12 mmol; nitrile: 48 mmol; hydro-
gen peroxide: 2 equiv (30% v/v aqueous solution); catalyst: 0.1 g;
peroxide: 2 equiv (30% v/v aqueous solution); catalyst: 0.1 g; T¼70 C;
surfactant (DBS): 0.6 mmol.
Conversion to lactone after 6 h.
Selectivity to lactone.
ꢁ
b
c
T¼70 C; surfactant (DBS): 0.6 mmol.
b
Conversion to 3-caprolactone after 6 h (in brackets conversion after 24 h).

1438
R. Llamas et al. / Tetrahedron 63 (2007) 1435–1439
acid a protons such as acetonitrile or phenylacetonitrile had
an adverse effect and resulted in considerably decreased
conversion relative to benzonitrile. As expected, acrylo-
nitrile provided better results than did the previous two
nitriles—it possesses no a protons—and matched those of
benzonitrile. Therefore, benzonitrile was the most effective
nitrile among those tested for the intended purpose.
0.4 mol of Mg(NO ) $6H O and 0.1 mol of Al(NO ) $9H O
3 2 2 3 3 2
in 250 mL of deionized water was used. This solution was
slowly dropped over 500 mL of an Na CO solution at pH
2
3
ꢁ
10 at 60 C under vigorous stirring. The pH was kept con-
stant by adding appropriate volumes of 1 M NaOH during
precipitation. The suspension thus obtained was kept at
ꢁ
80 C for 24 h, after which the solid was filtered and washed
with 2 mL of deionized water. The resulting hydrotalcite was
ion-exchanged with carbonate to remove intercalated ions
between layers. The procedure involved suspending the
solid in a solution containing 0.345 g of Na CO in 50 mL
of bidistilled, deionized water per gram of HT at 100 C
for 2 h. Then, the solid was filtered off in vacuo and washed
with 200 mL of bidistilled, deionized water. The HT thus
obtained was subjected to a second ion-exchange operation
under identical conditions as the first.
Once the reaction variables were optimized, we tested other
cyclic ketones and acetylpyridines as substrates for the
BV reaction. As can be seen, all cyclic ketones exhibited
2
3
ꢁ
1
2
00% conversion after 24 h of reaction; by exception,
-methyl- and 3-methylcyclohexanone fell short of com-
plete conversion by effect of the disparate migrating ability
of the methylene and methine groups observed in previous
2
3
work. Also, the presence of an ethylene bond conjugated
with the carbonyl group was found to decrease conversion
and selectivity towards the lactone by effect of competition
from the epoxidation reaction. Finally, acetylpyridines must
involve some kind of interaction between the electron pair
on the nitrogen atom in the ring and the catalyst surface as
4.3. Characterization of the hydrotalcite
Our HTwas characterized from its X-ray diffraction pattern,
2
7
which exhibited the typical signals for hydrotalcite. Its
empirical formula as established by elemental analysis was
Mg0.80Al0.20(OH) (CO ) $0.72H O.
2
-acetylpyridine exhibited lower conversion values than
did 3- and 4-acetylpyridine—where the nitrogen atom lies
farther from the catalyst surface (see Table 3).
2
3 0.10
2
4.4. General procedure for the Baeyer–Villiger
oxidation
3
. Conclusions
ꢁ
Baeyer–Villiger oxidation runs were performed at 70 C in
a two-neck flask containing 0.012 mol of carbonyl com-
pound, different amounts of nitrile, hydrogen peroxide,
catalyst and 0.6 mol of surfactant. One of the neck mouths
was fitted with a reflux condenser and the other was used
for sampling at regular intervals. The system was stirred
throughout the process. Products were identified from their
retention times as measured by GC–MS analysis on an
HP 5890 GC instrument furnished with a Supelcowax
30 mꢂ0.32 mm column and an HP 5971 MSD instrument.
The results obtained in this work confirm that catalysts
consisting of Mg/Al hydrotalcites provide excellent conver-
sion and selectivity in the Baeyer–Villiger reaction under
operating conditions that can be transferred to large-scale
work. The optimum benzonitrile/carbonyl substrate and
carbonyl substrate/hydrogen peroxide ratios are 4 and 2,
respectively. Under these conditions, conversion is also
affected by the nature of the solvent, methanol being the
best choice for the intended purpose. Also, benzonitrile is
the most suitable nitrile among those tested. Finally, tests
with alternative carbonyl compounds including cyclic
ketones and methyl ketones provided results that were also
consistent with the proposed mechanism. Only a,b-unsatu-
rated carbonyl compounds exhibited considerably decreased
conversion (a result of competition from epoxidation of their
double bonds).
4.5. Optimized procedure for the Baeyer–Villiger
oxidation
Optimized Baeyer–Villiger reaction runs were performed
at 70 C in a two-neck flask containing 0.012 mol of
carbonyl compound, 0.048 mol of benzonitrile, 2 equiv
of hydrogen peroxide, 0.1 g of catalyst (hydrotalcite),
ꢁ
0.6 mmol of sodium dodecylbenzenesulfonate and 5.2 mL
of methanol.
4. Experimental
4
.1. General
Acknowledgements
Mg(NO ) $6H O, Al(NO ) $9H O and H O (about 30%)
2 2
3
2
2
3 3
2
were purchased from Panreac. Ketones, solvents, nitriles
and surfactants were supplied by Aldrich and used without
further purification. All oxidation products were identified
by mass spectrometry.
The authors gratefully acknowledge funding by Spain’s
Ministerio de Educaci ꢀo n y Ciencia (Project MAT-2006-
04847), Feder Funds and the Consejer ꢀı a de Innovaci ꢀo n,
Ciencia y Empresa de la Junta de Andaluc ꢀı a.
4.2. General procedure for preparing the Mg/Al
hydrotalcite
References and notes
Hydrotalcite (HT) was prepared by mixing solutions of
Mg(NO ) $6H O and Al(NO ) $9H O in an Mg(II)/Al(III)
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