Aerobic oxidation of p-cresols to 4-hydroxy benzaldehydes catalyzed by cobaltous chloride/NHPI/salen-Cu(II) catalytic system

Article abstract of DOI:10.1007/s11164-013-1494-4

Oxidation of 2-methoxy-p-cresol, p-cresol, 2-bromo-p-cresol to their corresponding 4-hydroxybenzaldehydes with atmospheric molecular oxygen as oxidant and a combination of cobaltous chloride and N-hydroxyphthalimide (NHPI) as catalyst in methanol has been investigated for the first time. The results indicated that the reaction progress was related to the substituents in the structures of the substrates: the electron-donating group methoxy favors the aerobic reaction but the electron-withdrawing group Br is detrimental to the reaction. The introduction of salen-Cu(II) complexes as the third component into the cobaltous chloride/NHPI catalytic system can considerably improve the aerobic oxidation of p-cresol and 2-brom-p-cresol to the corresponding 4-hydroxybenzaldes.

Full text of DOI:10.1007/s11164-013-1494-4

Res Chem Intermed
DOI 10.1007/s11164-013-1494-4
Aerobic oxidation of p-cresols to 4-hydroxy
benzaldehydes catalyzed by cobaltous chloride/NHPI/
salen-Cu(II) catalytic system
•
•
•
Wenchan Ma Yuecheng Zhang Xiujuan Li
Jiquan Zhao
Received: 22 June 2013 / Accepted: 15 November 2013
Ó Springer Science+Business Media Dordrecht 2013
Abstract Oxidation of 2-methoxy-p-cresol, p-cresol, 2-bromo-p-cresol to their
corresponding 4-hydroxybenzaldehydes with atmospheric molecular oxygen as
oxidant and a combination of cobaltous chloride and N-hydroxyphthalimide (NHPI)
as catalyst in methanol has been investigated for the first time. The results indicated
that the reaction progress was related to the substituents in the structures of the
substrates: the electron-donating group methoxy favors the aerobic reaction but the
electron-withdrawing group Br is detrimental to the reaction. The introduction of
salen-Cu(II) complexes as the third component into the cobaltous chloride/NHPI
catalytic system can considerably improve the aerobic oxidation of p-cresol and
2-brom-p-cresol to the corresponding 4-hydroxybenzaldes.
Keywords p-cresol ꢀ 2-bromo-p-cresol ꢀ Aerobic oxidation ꢀ Cobaltous
chloride ꢀ N-hydroxyphthalimide ꢀ Cu(II)-salen complexes
Introduction
4-Hydroxybenzaldehydes are important chemical intermediates for preparing phar-
maceuticals, pesticides, fragrances, petrochemicals, and electroplating chemicals [1–
3]. For example, vanillin (4-hydroxy-3-methoxybenzaldehyde) is the major compo-
nent of vanilla, which is one of the most widely used and important flavoring materials
worldwide [4, 5]; 3,5-dimethyl-4-hydroxy benzaldehyde is used for the synthesis of
potential antioxidant cancer chemopreventive agents [6]. Methods that have been
employed to synthesize 4-hydroxybenzaldehydes include reacting phenols with
formaldehyde [7], glyoxylic acid [8], or chloroform [9, 10], and the use of
stoichiometric amounts of inorganic oxidants [11–14]. All these methods suffer from
W. Ma ꢀ Y. Zhang ꢀ X. Li ꢀ J. Zhao (&)
School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130,
People’s Republic of China
e-mail: zhaojq@hebut.edu.cn
123

W. Ma et al.
one or more disadvantages such as consuming high energy, using heavy metal
catalysts, and generating large amounts of inorganic salts as by-products, which may
cause serious environmental problems [15]. Increasing the awareness towards a clean
environment, the catalytic partial oxidation of 4-cresols or 4-hydroxybenzyl alcohols
with molecular oxygen to 4-hydroxybenzaldehydes is an attractive new alternative for
the synthesis of 4-hydroxybenzaldehydes. Many catalysts or catalytic systems have
been developed to achieve these transformations [15–19]. Among all the methodol-
ogies, the aerobic oxidation of 4-cresols catalyzed by cobalt-based catalysts in strong
basic medium is the most attractive and has been studied in detail.
Recently, we successfully used a combination of cobaltous chloride and N-hydrox-
yphthalimide (NHPI) as catalyst and atmospheric molecular oxygen as oxidant to oxidize
2-methoxy-p-cresol to vanillin (4-hydroxy-3-methoxybenzaldehyde) in methanol [20].
Under the optimized conditions, the yield of vanillin was 90.1 %. However, when the
combination catalyst was applied to the oxidation of p-cresol and 2-brom-p-cresol under
the same conditions, low reaction conversions and yields were received. It was learned
from the literature that 4-hydroxybenzyl alcohols as intermediates are involved in the
transformation of 4-cresols to 4-hydroxybenzaldehydes; meanwhile, p-hydroxybenzoic
acids and 4-hydroxybenzyl methyl ether as by-products could be formed in the process
(Scheme 1) [15, 21, 22]. GC analysis confirmed that the low selectivity of 4-hydroxy-
benzaldes is mainly due to a considerable amount of 4-hydroxybenzyl alcohols present in
the reaction mixtures. If the 4-hydroxybenzyl alcohols are oxidized further to
4-hydroxybenzaldehydes, the yields can be greatly improved.
It has been found in the literature that salen-Cu(II) complex/TEMPO [23] and bis
(3,5-di-tert-butyl salicylaldimine) copper(II) complexes/TEMPO [24] systems are
highly efficient for the aerobic oxidation of primary benzylic and allylic alcohols to
their corresponding aldehydes under mild reaction conditions. However, the
catalytic systems are generally of high cost due to the use of the expensive TEMPO.
NHPI is similar to TEMPO in function but much cheaper, which may become an
alternative to TEMPO in the aerobic oxidation of alcohols. This idea in combination
with our experience in the synthesis and application of salen-metal complexes [25–
27] inspired us to introduce salen-Cu(II) complexes into the cobaltous chloride/
NHPI system, which constructs three-component catalytic systems, to improve the
aerobic oxidation of p-cresol and 2-brom-p-cresol to their corresponding hydrox-
yaldehydes. It has been found that the three-component catalytic systems are very
effective in improving the oxidation reaction. Here, we report the results.
Materials and methods
Materials and apparatus
Salen-Cu(II) complexes were synthesized using the method in the literature [28].
NHPI was purchased from Acros Organics. 2-Methoxy-p-cresol, p-cresol, 2-bromo-p-
cresol cobaltous chloride (CoCl2ꢀ6H2O), sodium hydroxide (NaOH), and HPLC-
grade methanol, acetonitrile, and phosphoric acid were obtained from Tianjin
Fuchen Chemical Reagent Factory, China. All the chemicals were used as received.
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Aerobic oxidation of p-cresols
CHO
CO2H
O2
O2
X
X
CH3
CH2OH
OH
OH
O2, NaOH
X
X
5
3
Catalyst, CH3OH
CH2OCH3
OH
OH
1
2
X
CH3OH
OH
4
Scheme 1 Pathways for the formation of hydroxybenzaldehydes and by-products
HPLC experiments were performed with a Shimadzu (Kyoto Japan) SPD-10ATvp
plus chromatograph equipped with an SPD-10Avp detector and C18 reversed-phase
column (4.6 mm i.d. 9250 mm). The mobile phase was 25 % acetonitrile–water
containing 0.1 % phosphoric acid.
Catalytic Procedure
Oxidation reactions were conducted in a 10-ml two-necked flask equipped with a
condenser and a thermometer. A balloon filled with oxygen was connected to the
top of the condenser. All reactions were conducted at atmospheric pressure and
stirred with an electromagnetic stirrer at a constant rate.
In a typical process, a mixture of NaOH (10.9 mmol) and methanol (2.0 ml) was
introduced into the flask. The mixture was vigorously stirred at room temperature.
When the NaOH had completely dissolved, 2-bromo-p-cresol (3.62 mmol) was
added and the mixture was stirred for half an hour to ensure the substrate had been
converted into its sodium salt. Cobaltous chloride, NHPI, and salen-Cu(II) complex
were then quickly added. Chilled water was circulated through the condenser to
minimize loss of the solvent. The mixture was heated to the desired temperature
(65 °C), then the oxygen from the balloon was introduced, and controlled by use of
a triple valve. After a specific time, the introduction of oxygen was stopped and the
reaction mixture was left to cool to room temperature. The cooled reaction mixture
was analyzed as described below.
Analysis of the reaction mixture
After the reaction, the whole reaction mixture was accurately weighed to obtain the
total weight (wt). An accurately weighed amount (approx. 0.1 g) of the reaction
mixture (w0) was placed in a 10-ml volumetric flask, then an appropriate amount of
123

W. Ma et al.
concentrated hydrochloric acid was added to neutralize the NaOH. The neutralized
mixture was dissolved in mobile phase to a constant volume. The amounts of
p-cresols and 4- hydroxyaldehydes (ws0 and wv0) were determined by HPLC with
use of an external standard.
The weight of 4-hydroxybenzaldehydes in the reaction mixture can be obtained
by use of Eq. 1:
À
Á
wp ¼ wt ꢁ wp0 = w0ðgÞ
The weight of p-cresols left in the reaction mixture can be obtained by use of
ð1Þ
Eq. 2:
ws ¼ ðwt ꢁ ws0Þ= w0ðgÞ
moles of p-cresol reduced
ð2Þ
ð3Þ
Conversion ð%Þ ¼
ꢁ A0100%
moles of p-cresol charged
moles of p-hydroxybenzaldehydes obtained
moles of p-cresol reduced
Selectivity ð%Þ ¼
ꢁ A0100% ð4Þ
ð5Þ
Yield ð%Þ ¼ Conversion ꢁ Selectivity
Results and discussion
First, liquid-phase oxidation of 2-methoxy-p-cresol (A), p-cresol (B), 2-brom-p-
cresol (C) to their corresponding 4-hydroxybenzaldehydes was carried out by using
the combination of cobaltous chloride and N-hydroxyphthalimide (NHPI) as
catalyst in the presence of NaOH in methanol under atmospheric oxygen pressure.
The reaction results under optimized conditions are listed in Table 1.
It can be seen that 2-methoxy-p-cresol and p-cresol were oxidized to vanillin and
4-hydroxybenzaldehyde in excellent and moderate yields, respectively. However,
2-bromo-p-cresol was converted to 3-bromo-4-hydroxybenzaldehyde only in low
conversion and yield. These results indicated that the catalytic aerobic oxidation of
p-cresols to hydroxybenzaldes is related to the substituents in the structures of the
substrates. The electron-donating group facilitates the oxidation reaction; in
contrast, the electron-withdrawing group is unfavorable to the reaction. As
described in the ‘‘Introduction’’, the low yield of the reaction is mainly due to a
considerable amount of the 4-hydroxybenzyl alcohols not being converted to their
corresponding 4-hydroxybenzaldes. Therefore, two salen-Cu(II) complexes (1 and
2) were respectively introduced to the system to construct three-component catalysts
to improve the oxidation reaction. The results are present in Table 2. It can be seen
that both complexes can improve the selectivity towards 4-hydroxybenzalde in the
oxidation of p-cresol; c1 performed better than c2 in view of the selectivity and
yield of 4-hydroxybenzalde. When the molar ratio of c2 to p-cresol was 0.46 %, the
selectivity of hydroxybenzalde increased from 74.4 to 83.9 %. The poor perfor-
mance of c2 compared to c1 on the improvement of the selectivity of the target
product is due to the fact that c2 is more active than c1 in promoting the
transformation
of
the
intermediate
4-hydroxybenzy
alcohol
to
123

Aerobic oxidation of p-cresols
Table 1 Aerobic oxidation of p-cresols catalyzed by CoCl2/NHPI
Entry
Sub
NaOH/Sub
(mol/mol)
Methanol
(ml)
Conversion
(%)
Selectivity
(%)
Yield
(%)
1
2
3
A
B
C
6.0:1
3.5:1
3.0:1
3
3
2
100.0
93.6
33.6
90.1
74.4
72.0
90.1
69.3
24.2
Reaction conditions: substrate 3.62 mmol; cobaltous chloride 0.0173 mmol; NHPI 0.0725 mmol; reac-
tion temperature 65 °C; reaction time 7 h; atmospheric oxygen pressure
Table 2 Aerobic oxidation of p-cresols catalyzed by CoCl2/NHPI/salen-Cu(II)
Entry
Sub
Salen-Cu(II)
Time (h)
Conversion (%)
Selectivity (%)
Yield (%)
1
2
3
4
5
6
Ba
Ba
Cb
Cb
Cb
Cb
c1
c2
c1
c2
c2
c2
7
7
5
5
7
9
94.8
97.3
35.6
52.3
56.8
57.2
83.9
76.3
77.0
82.4
89.3
86.5
79.5
74.2
27.4
43.1
50.7
49.5
Reaction conditions: substrate 3.62 mmol; cobaltous chloride 0.0173 mmol; NHPI 0.0725 mmol; salen-
Cu(II) 0.0166 mmol (salen-Cu(II) : substrate = 0.46 %); reaction temperature 65 °C; reaction time 7 h;
atmospheric oxygen pressure
a
NaOH:substrate = 3.5:1, methanol 3 ml
b
NaOH:substrate = 3.0:1, methanol 2 ml
4-hydroxybenzaldehyde, and then leading to more 4-hydroxybenzoic acid formation
from the further oxidation of 4-hydroxybenzaldehyde in the reaction system.
In the case of 2-bromo-p-cresol as substrate, both the complexes can obviously
also increase the conversion of 2-bromo-p-cresol and the selectivity of the target
product, but the conversion and selectivity are still low. Prolonging the reaction
time can increase the conversion of 2-bromo-p-cresol gradually, while the
selectivity of the target product also increased with reaction time at the beginning,
but began to decrease when the conversion was higher than 56.8 %. No further
improvement on the oxidation of 2-bromo-p-cresol was received by changing the
reaction parameters.
To our knowledge, no catalytic oxidation of 2-bromo-p-cresol with molecular
oxygen has been reported in the literature. However, many homogeneous and
heterogeneous catalysts for the oxidation of 4-hydroxybenzy alcohol with molecular
oxygen can be retrieved [16, 21, 22, 29]. For comparison, Table 3 presents the
catalytic results of the current three-component catalyst and the other catalysts
reported recently. It can be seen that the current three-component catalyst performed
better than the other homogeneous catalysts reported in the literature in the
conversion and selectivity towards 4-hydroxybenzalde. The heterogeneous catalysts
123

W. Ma et al.
Table 3 Comparison of the current three-component catalyst with the other catalysts in the literature
Catalyst
Type
Pressure Temperature Conversion Selectivity Ref.
(MPa)
(°C)
(%)
(%)
CoCl2/NHPI/c1 Homogeneous
TPPCo Homogeneous
0.1
0.1
0.1
65
70
65
94.8
69.6
37.0
83.9
66.0
88.0
This study
[15]
Co(salen)-Mont Immobilized
homogeneous
[28]
PVDF-CoP2O7
Co3O4
Heterogeneous
Heterogeneous
1.0
0.8
75
94.2
98.0
94.4
95.0
[29]
[21]
100
showed good performances compared to the current catalyst; however, harsh
reaction conditions such as high oxygen pressure and reaction temperature were
required.
It is well known that Co/NHPI can efficiently catalyze the oxidation of alkanes
with molecular oxygen, and the mechanism has been described in detail by Ishii
[30]. The initial step is the complexation of Co(II) with O2 to generate a labile
dioxygen complex such as superoxocobalt(III). The second step is the formation of
the free radical PINO by the reaction of the NHPI with the cobalt(III)–oxygen
complex. The third step in the oxidation involves the hydrogen abstraction from RH
by the PINO to form Rꢀ, which is readily trapped by dioxygen to provide ROOꢀ
followed by ROOH and eventually the formation of alcohols, ketones, and/or
carboxylic acids (Fig. 1).
CoII + O2
CoIII
O
O
ð6Þ
O
O
CoIII
O
NOH
+
CoIII
OH
O
+
O
NO
ð7Þ
O
O
NHPI
PINO
In the current three-component catalyst, the formed free radical PINO also
combined with salen-Cu(II) to promote the oxidation of 4-hydroxybenzy alcohol,
being an intermediate in the oxidation of p-cresol to 4-hydroxybenzaldehyde. A
plausible pathway for the salen-Cu(II)-promoted oxidation of the 4-hydroxybenzy
alcohol to 4-hydroxybenzaldehyde is shown in Fig. 2. The 4-hydroxybenzy alcohol
firstly coordinates with the central Cu(II) of the salen-Cu(II) complex, where one of
the phenoxide groups is converted to phenol [31–33]. Subsequently, an intramole-
cular abstraction of b-hydrogen with PINO occurs and the corresponding aldehyde,
NHPI, and Cu(I) species are formed. In the presence of oxygen superoxocobalt(III)
generated from Co(II) and oxygen, the PINO is regenerated back to PINO;
meanwhile, the oxygen reoxidizes the Cu(I) species back to the original salen-Cu(II)
complex [24].
123

Aerobic oxidation of p-cresols
Fig. 1 Structures of salen-
Cu(II) complexes
N
O
N
O
Cu
R
R
R
R
c1: R = H; c2: R = C(CH3)3
H
N
O
N
CuII
H
H2O
Ph
O
OH
O2
N
O
N
CuII
H
N
N
CuI
OH
O
Ph
O
O
OH
H
H
Ph
CoIII
O
O
NHPI
PINO
R
N
O
N
CuII
Salen Cu(II) complex
;
Ph =
=
OH
O
Fig. 2
4-hydroxybenzaldehydes catalyzed by salen-Cu(II)
A
plausible pathway for the oxidation of the 4-hydroxybenzy alcohols to
It is worth mentioning that our purpose in investigating the aerobic oxidation of
2-methoxy-p-cresol, p-cresol, and 2-bromo-p-cresol to the corresponding 4-hy-
droxybenzaldes is to establish a route for synthesizing vanillin from p-cresol. In
principle, there are three possible synthetic routes (a, b, and c) to vanillin from
p-cresol as shown in Scheme 2. The respective oxidation of 2-methoxy-p-cresol,
p-cresol, and 2-bromo-p-cresol is one elementary step in the corresponding
synthetic routes. Due to the very low conversion and selectivity towards 3-bromo-4-
hydroxybenzaldehyde in the aerobic oxidation of 2-brom-p-cresol, route b can be
excluded from the synthesis of vanillin from p-cresol.
123

W. Ma et al.
CH3
OMe
O2
MeO-
OH
CHO
CH3
CH3
a
CHO
Br2
O2
MeO-
Br
Br
b
OMe
OH
OH
CHO
OH
OH
O2
Br2
c
OH
Scheme 2 Possible routes for synthesis of vanillin from p-cresol
Conclusions
The cobaltous chloride/NHPI catalyzed aerobic oxidation of p-cresols to the
corresponding 4-hydroxybenzaldes is related to the structures of the substrates. The
electron-donating group facilitates the oxidation reaction; in contrast, the electron-
withdrawing group is unfavorable to the reaction. The introduction of salen-Cu(II)
complexes as the third component into the cobaltous chloride/NHPI catalytic system
can obviously improve the aerobic oxidation of p-cresol and 2-brom-p-cresol to the
corresponding 4-hydroxybenzaldes.
Acknowledgment The authors are grateful for financial support from the National Natural Science
Foundation of China (No. 21276061).
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