The efficient catalytic oxidation of 2,3,6-trimethylphenol with air over composite catalyst to synthesize Vitamin E intermediate

Article abstract of DOI:10.1007/s11164-021-04500-z

2,3,5-Trimethylbenzoquinone (TMBQ)is a kind of crucial intermediate in the synthesis of Vitamin E, whose demand is increasing rapidly. The traditional synthesis method of TMBQ needs H₂O₂ or pure O₂ as the oxidant, which is expensive and needs much attention in the production, transportation and storage process. In order to overcome the issues, the green oxidant, air, has been developed in this work to prepare TMBQ for the first time. TMBQ was synthesized from 2,3,6-trimethylphenol (TMP) with the oxidant of air in the solvent of isoamylol catalyzed by composite catalyst of inorganic salts at one atmosphere pressure. The critical reaction parameters, including the ingredient of composite catalyst, reaction time, reaction temperature, stirring speed and the addition of ionic liquids were investigated in order to achieve the optimal reaction condition. TMBQ was obtained with the conversion of 100% and selectivity of 96.7% at 90?°C for 7–8?h at one atmosphere pressure, over the composite catalyst, the aqueous solution of CuCl₂, FeCl₃ and MgCl₂, with the help of ion liquid, 1-sulfobutyl-3-methylimidazole hydrochloride ([Bmim]Cl). Moreover, the catalyst could be recycled more than four times. Air is very cheap, abundant, eco-friendly and safe in production, transportation and storage process. The synthesis of TMBQ from TMP with air as oxidant at one atmosphere pressure has obvious advantages, which will bring new inspiration for the industrial production of TMBQ. Graphic abstract: [Figure not available: see fulltext.].

Full text of DOI:10.1007/s11164-021-04500-z

Research on Chemical Intermediates
https://doi.org/10.1007/s11164-021-04500-z
The efcient catalytic oxidation of 2,3,6‑trimethylphenol
with air over composite catalyst to synthesize Vitamin E
intermediate
Tianyong Zhang1,2 · Yuxin Song1 · Yang Yang1 · Bin Li1 · Shuang Jiang1
Received: 26 February 2021 / Accepted: 22 May 2021
© The Author(s), under exclusive licence to Springer Nature B.V. 2021
Abstract
2,3,5-Trimethylbenzoquinone (TMBQ)is a kind of crucial intermediate in the syn-
thesis of Vitamin E, whose demand is increasing rapidly. The traditional synthesis
method of TMBQ needs H2O2 or pure O2 as the oxidant, which is expensive and
needs much attention in the production, transportation and storage process. In order
to overcome the issues, the green oxidant, air, has been developed in this work to
prepare TMBQ for the frst time. TMBQ was synthesized from 2,3,6-trimethylphe-
nol (TMP) with the oxidant of air in the solvent of isoamylol catalyzed by composite
catalyst of inorganic salts at one atmosphere pressure. The critical reaction param-
eters, including the ingredient of composite catalyst, reaction time, reaction temper-
ature, stirring speed and the addition of ionic liquids were investigated in order to
achieve the optimal reaction condition. TMBQ was obtained with the conversion
of 100% and selectivity of 96.7% at 90 °C for 7–8 h at one atmosphere pressure,
over the composite catalyst, the aqueous solution of CuCl2, FeCl3 and MgCl2, with
the help of ion liquid, 1-sulfobutyl-3-methylimidazole hydrochloride ([Bmim]Cl).
Moreover, the catalyst could be recycled more than four times. Air is very cheap,
abundant, eco-friendly and safe in production, transportation and storage process.
The synthesis of TMBQ from TMP with air as oxidant at one atmosphere pressure
has obvious advantages, which will bring new inspiration for the industrial produc-
tion of TMBQ.
*
*
Bin Li
libin@tju.edu.cn
Shuang Jiang
shuangjiang@tju.edu.cn
1
2
Tianjin Key Laboratory of Applied Catalysis Science and Technology, School of Chemical
Engineering and Technology, Tianjin University, Tianjin 300354, People’s Republic of China
Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University,
Tianjin 300354, People’s Republic of China
Vol.:(0123456789)
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T. Zhang et al.
Graphic abstract
Keywords 2,3,6-Trimethylphenol · 2,3,5-trimethylbenzoquinone · Air oxidation ·
Catalysis · Ionic liquid
Introduction
Vitamin E, also known as α-tocopherol, is a kind of fat soluble vitamin, which
widely exists in green plants and slightly in animals [1]. The defciency of Vitamin
E could cause muscle atrophy and other diseases [2]. Vitamin E is widely used as
nutrients, antioxidants and additives of drugs and feed, and its demand is increasing
rapidly in recent decades [3]. As the natural Vitamin E is very limited, the demand
for synthetic Vitamin E is rapidly increasing. 2,3,5-Trimethylbenzoquinone (TMBQ)
is an essential intermediate for the synthesis of Vitamin E [4–7]. The industrial
production of Vitamin E needs several steps with corresponding key intermedi-
ates (Scheme 1). Thereinto, TMBQ is the inevitable intermediate which has two
mainly reported industrial production routes. On one hand, metacetone and 1-amino
Scheme 1 The synthesis route of Vitamin E
1 3

The efcient catalytic oxidation of 2,3,6‑trimethylphenol…
vinylmethyl ketone reacts to produce 2, 3, 6-trimethylphenol (TMP), which was then
oxidized to get TMBQ [8]. On the other hand, 1,2,4-trimethylbenzene could be syn-
thesized into TMBQ [7]. Even though 1,2,4-trimethylbenzene is cheap but the syn-
thesis route of TMBQ from it is long and always gives a low yield [7]. Afterward,
TMBQ is reduced to obtain 2,3,5-trimethylhydroquinone (TMHQ), which then con-
denses with isophytol and esterify to obtain Vitamin E [6].
The developed synthesis methods of TMBQ include the oxidation of TMP and
trimethylbenzene, but the latter has not been employed in the industry [5–7]. The
preparation of TMBQ from TMP is widely popular in industry, and the direct oxi-
dation of TMP is the focus recently [9]. According to the reports, oxygen or perox-
ides are mostly used as oxidants in the solvents like alcohols, toluene, ether, ace-
tonitrile or other organic solvents. The catalyst systems include copper based and
cobalt based catalysts, alkali metal and alkaline earth metal halides, transition metal
halides, heteropoly acid catalytic systems or ionic liquids [6]. Among the catalysts
in oxidation reactions, copper based catalysts are cheap and easy to get, which have
shown good catalytic efciency to obtain high reaction yield [10]. In the technical
process of TMP, CuCl2 and LiCl were employed as catalyst with the oxidant of O2
to achieve the yield of 96% with the pressure of oxygen from 0.03 to 0.1 MPa [6,
11, 12]. Yerramreddy et al. reported the preparation of TMBQ from TMP in the
presence of the H2O2 oxidant and catalyst of spinel CuCo2O4 [7]. They obtained an
80% yield of TMBQ. Li et al. [5] reported the oxidation of TMP to TMBQ with the
Fenton’s reagent (H2O2 and FeSO4) under mild conditions. Selvaraj et al. [13–15]
also reported the selective synthesis of TMBQ and derivate from TMP and cor-
responding phenol with H2O2 as the oxidant with high selectivity and conversion.
However, H2O2 is corrosive and is dangerous in terms of transportation and storage.
The explosive properties of high concentration H2O2, especially when combined
with metal salts, may cause serious safety problems [16]. Oxygen is dangerous and
also has the problem of transportation and storage. Besides, the consumption of O2
and H2O2 in the industrial production costs much more, especially compared with
air. Therefore, it is imperative to develop more natural and safe oxidants. Among the
reported oxidation reactions to synthesize TMBQ, all are heterogeneous catalytic
reactions as far as we know. Even though the reactants and catalyst are potential to
contact and react more adequately in homogeneous catalytic reactions, yet it brings
difculty in the separation and reuse of catalyst.
Ionic liquids have high heat capacity, low vapor pressure, stable properties and
good solubility for many inorganic salts and organic compounds [17]. In recent
years, ionic liquids have been widely used in the felds of electrochemistry, organic
synthesis, catalysis and separation [17]. Sun et al. used CuCl2 as catalyst and 1-butyl-
3-methylimidazolium chloride ([Bmim]Cl) as cocatalyst to catalyze the oxidation
of TMP to TMBQ under oxygen, which showed that ionic liquid was a very good
cocatalyst for the oxidation of TMP, due to the synergistic efect between [Bmim]
Cl and CuCl2 [18, 19]. Recently, more and more cases about wet air oxidation have
been reported, which has inspired us in the preparation of TMBQ [20]. Air is cheap,
clean, stable, convenient, abundant and easy to get as a rich natural resource. If air
can be used as oxidant for direct oxidation reaction especially at mild pressure, it
will avoid many problems, bring convenience, reduce costs and simplify the process.
1 3

T. Zhang et al.
Therefore, we developed the direct air oxidation method at one atmosphere pressure
to oxidize TMP to TMBQ for the frst time. With the catalysis of inorganic salt and
ionic liquid, we explored the infuence of reaction parameters, and obtained an ef-
cient production process of TMBQ from TMP directly oxidized by air. TMBQ was
obtained with a selectivity of 96.7% at 100% conversion of TMP at 90 °C for 7–8 h
at one atmosphere pressure with the usage of composite catalyst, in the presence of
[Bmim]Cl. At the same time, the oxidation mechanism was proposed.
Experimental
Materials
TMP is from Nantong Baisheng Company. Isoamylol, CuCl2·2H2O, MgCl2·6H2O,
CoCl2·6H2O and FeCl3·6H2O were from Sinopharm Chemical Reagents Co. Ltd.
1-Butyl-3-methylimidazolium hydrochloride ([Bmim]Cl), 1-butyl-3-methylimida-
zolium tetrafuoroborate ([Bmim]BF4), 1-butyl-3-methylimidazolium trifuorometh-
anesulfonate ([Bmim]CF3SO3), 1-butyl-3-methylimidazolium disulfate [Bmim]
HSO4, 1-butyl-3-methylimidazolium dihydrogen phosphate ([Bmim]H2PO4) were
from Shanghai Chengjie Chemical Co., Ltd.
Synthesis of TMBQ
The synthesis route of TMBQ is shown in Scheme 2. With the proper cata-
lyst, TMBQ is obtained with a small part of byproduct, 2,2’,3,3’,5,5’-hexame-
thyl-4,4’–diphenol. In a typical procedure, the aqueous solution of catalyst Y (630 g)
and isoamylol were charged into a vessel. TMP (80 g) was dissolved into isoamylol
(300 mL) and charged in the dropping funnel. The temperature was increased to the
reaction temperature. The air was blown into the reaction solution with an air pump
with the fow rate of 1L/min to control the pressure at one atmosphere pressure.
The reaction system was stirred at certain stirring speed. The TMP solution in the
dropping funnel was dropped into the reaction system. The reaction was monitored
with gas chromatography (GC). At the end of the reaction, the mixture was divided
with a separating funnel. 40 g of water was added into the upper organic layer and
washed fve times separately. The water obtained for the frst washing was recycled
Scheme 2 The synthesis route of TMBQ
1 3

The efcient catalytic oxidation of 2,3,6‑trimethylphenol…
with the catalyst for further reaction. The organic layer was analyzed with GC. The
lower aqueous layer will be collected and supplemented with catalyst for reuse.
Results and discussion
Catalytic oxidation of TMP
CuCl2, Fe(III) aquacomplex and Fenton reagent have been reported as efective cat-
alysts for the oxidation of TMP and other oxidation reactions due to the catalytic
oxidation activity of the ion salt [5, 6, 21, 22]. Herein, the mixture of CuCl2 and
FeCl3 (marked as Y for short) was used as catalyst. In the initial catalytic oxidation
reaction, TMP was oxidized with the catalyst of Y in the solvent isoamylol. The
ratio of Y to TMP was investigated and found that when 90 g of TMP dissolved in
270 mL of isoamylol with the addition of 630 g of Y solution, the highest yield of
TMBQ was achieved, 92.5% after 16 h of reaction. According to the related reports,
there was a kind of byproduct, 2,2′,3,3′,5,5′-hexamethyl-4,4′-diphenol, and interme-
diate product, 4-chloro-2,3,6-trimethylphenol (TMPCl), respectively [9]. The gen-
eration of 2,2′,3,3′,5,5′-hexamethyl-4,4′-diphenol and the incomplete transformation
of TMPCl contributes to the 7.5%. Compared with typical reaction oxidized by O2
or H2O2, the concentration of oxidant, O2, involved in the reaction is greatly reduced
in the direct air oxidation way. What’s more, the pressure of air was expected at one
atmosphere pressure to achieve mild condition. Therefore, it is necessary to improve
the intensity of catalytic oxidation. The optimal catalyst has been investigated based
on the original catalyst Y. As to the choice of solvent, the usage of alcohol solvent
always leads to a high yield according to the reports [6]. The boiling point should
be high enough for this reaction. Therefore, isoamylol, hexyl alcohol and n-heptanol
have been considered for the reaction. In the biphasic liquid reaction system, the
high mutual solubility is beneft to the adequate contact of catalyst and reactants.
The order of solubility in water is: isoamylol (28 g/L) > exyl alcohol (6 g/L) >
n-heptanol (2.8 g/L). Therefore, isoamylol is chosen as the solvent. To achieve the
best catalytic performance, several infuence factors has been explored including
cocatalyst, temperature, and stirring speed.
The exploration of catalyst
The reported reactions to prepare TMBQ are heterogeneous catalytic reactions.
Inorganic metal salts, like the salts or mesostructured compounds containing Co,
Cu and other metals, have been used as catalysts in the oxidation of TMP to TMBQ
[7, 16–18, 23]. The related studies have shown that LiCl has a positive efect on
the reaction [24]. However, the needed ratio of Li to TMP is large and Li is too
expensive for the industrial usage. Therefore, chloride of alkaline earth metal Mg
is considered. Therefore, in order to improve the catalytic performance, MgCl2 and
CoCl2 were added into the original catalyst Y to form a new catalyst. Meanwhile,
1 3

T. Zhang et al.
the optimum ratio of CuCl2 and FeCl3 was explored and they were added to Y,
respectively, to investigate the catalytic oxidation performance.
The catalytic performance of catalyst Y with inorganic salts was studied. It can
be seen from Table 1 that when 4 g of MgCl2·6H2O is added, the reaction time
is shortened by 5 h, and the selectivity increased from 92.5 to 95.5%, indicating
that the addition of MgCl2 can signifcantly promote the reaction. As the amount
of MgCl2·6H2O increased to 12 g, the reaction selectivity get higher, but too much
MgCl2 will bring difculty in the later separation of water and oil. Therefore, adding
4 g of MgCl2·6H2O is appropriate. With the addition of CuCl2, the reaction time was
signifcantly prolonged, but the selectivity only improved slightly. The original cata-
lyst Y contained enough CuCl2, which has got the optimal ratio with TMP. When
FeCl3 and CoCl2 were added, the selectivity of the catalytic reaction was slightly
improved to 94–95%. Mg2+, Cu2+ Fe3+ and Co2+ metal ions can promote the activa-
tion of TMP to phenoxy radical, and the presence of Cl− is also conducive to the
conversion of intermediate products to target products, leading to the increase in
conversion rate. However, the induction of CuCl2, FeCl3 and CoCl2 will darken the
color of the mixture, which makes it hard to judge the interface between water and
oil in the later separating process. On the contrary, MgCl2 aqueous solution is color-
less, conducive to judge the interface. Therefore, 4 g MgCl2·6H2O is selected to
combine with Y as the new catalyst in the catalytic oxidation reaction.
Table 1 The catalytic
Entrya
Amount (g)
Reaction time (h)
Selectivity
of TMBQ
(%)f
performance with diferent
addition of inorganic salt as
catalyst
Control
1b
0
2
4
8
12
2
4
8
16
2
13.5
8
8.5
10.5
12
19
19
21
20
92.5
88.9
95.5
93.5
96.7
92.3
85.7
84.0
93.3
94.4
94.1
95.0
94.6
2b
3b
4b
5c
6c
7c
8c
9d
8.5
10
8.5
10d
11e
12e
4
2
4
12
aTemperature of 90 °C and stirring speed of 700 r/min
bMgCl2·6H2O
cCuCl2·2H2O
dFeCl3·6H2O
eCoCl2·6H2O
fConversion of 100%
1 3

The efcient catalytic oxidation of 2,3,6‑trimethylphenol…
Efect of ionic liquid
Ionic liquid [Bmim]BF4 has been employed as an efective solvent and cocatalyst
in the oxidation of TMP to TMBQ [9, 25]. In other oxidation reactions, ionic liq-
uid has also been proved efective. Besides, ionic liquid could work together with
Cu2+-based catalyst [26]. Herein, several ionic liquids, including [Bmim]Cl and
[Bmim]BF4 have been investigated in the direct air oxidation of TMP. It is shown
in Table 2 that the reaction time is efectively shortened from 13.5 h to 7–10 h, and
the selectivity of TMBQ reaches 96.3% after adding 0.2–1.0 g of [Bmim]Cl. When
0.5 and 0.8 g of [Bmim]BF4 were added, the reaction time was shortened to 7 and
8 h, with the selectivity of 95.2 and 95.8%, respectively. However, if the amount of
[Bmim]Cl or [Bmim]BF4 is too much or little, the improvement of reaction efect
is limited or even worse than the original reaction condition, indicating that there is
an optimal amount of ionic liquid. Ionic liquids could promote the reaction for two
reasons: (1) [Bmim]Cl/[Bmim]BF4 acts as the cocatalyst. There is the synergistic
efect between [Bmim]Cl /[Bmim]BF4 and the CuCl2/FeCl3, which is conducive to
the formation of reaction intermediates, thus efectively promoting the reaction; (2)
the addition of imidazolyl ionic liquid promoted the miscibility of water phase and
Table 2 The catalytic
Entrya
Amount (g)
Reaction time (h)
Selectivity
of TMBQ
(%)f
performance with addition of
ionic liquid
Control
1b
0
13.5
9.5
9
8
10
7
13
7
8
10
16
11
9
92.5
95.6
96.3
93.4
93.4
94.7
86.1
87.9
5.2
95.8
93.2
89.1
94.1
93.8
93.8
0.2
0.5
0.8
1.0
1.2
0.2
0.5
0.8
1.0
1.2
0.2
0.5
0.2
0.5
2b
3b
4b
5b
6c
7c
8c
9c
10c
11d
12d
13e
14e
13.5
8
aTemperature of 90 °C and stirring speed of 700 r/min
b[Bmim]Cl
c[Bmim]BF4
d[Bmim]HSO4
e[Bmim] CF4SO3
fConversion of 100%
1 3

T. Zhang et al.
oil phase, resulting in the sufcient contact between TMP and catalyst, which accel-
erated the reaction [9].
In the oxidation process of TMP, the acidity of ionic liquid showed an infuence
on the selectivity of TMBQ. In the oxidation of aromatic hydrocarbons to quinones,
Brønsted acids, such as glacial acetic acid and acetic anhydride, were used as cata-
lysts [27]. In order to investigate the efect of acidity on the reaction, diferent acidic
ionic liquids [Bmim]H2PO4, [Bmim]HSO4, [Bmim]CF3SO3H were employed. The
results showed that the selectivity of the reaction was slightly improved to around
94% (Table 3). As a result of the investigation of ionic liquid, 0.2–1.0 g of [Bmim]
Cl or 0.5–0.8 g of [Bmim]BF4 has been proven as the optimal reaction conditions.
Based on the above research, the comprehensive catalytic performance of Y,
MgCl2 and [Bmim]Cl/[Bmim]BF4 were investigated. It is shown in Table 3 that
when 4 g of MgCl2·6H2O and 0.5 g of [Bmim]Cl are added, the reaction time is
8 h, and the selectivity of TMBQ is as high as 96.7%. When MgCl2 and 0.5 g of
[Bmim]BF4 were added, the selectivity of TMBQ was 94%—95%, which was lower
than that of [Bmim]Cl. The reason may be as follows: The addition of MgCl2 and
[Bmim]Cl is benefcial to the formation of intermediates and improves the selec-
tivity of the reaction. When MgCl2 and [Bmim]BF4 were added, the selectivity of
−
TMBQ was lower, due to the large volume of BF4 which hindered the formation
of intermediates. Consequently, 4 g of MgCl2·6H2O and 0.5 g of [Bmim]Cl was
selected as the optimum conditions for the following research of reaction tempera-
ture, stirring speed and recycle of catalysts.
Efect of temperature
There was no noticeable change in the reaction time, which fuctuates between 7
and 8 h, as the reaction temperature varied from 50 to 90 °C, as shown in Fig. 1.
The yield of TMBQ increased from 90.3 to 96.7%, undergoing a decrease to 88.6%
at 60 °C, with the increase in temperature. The formation of active intermediates is
Table 3 The catalytic
Entrya
Reaction time (h)
Selectivity of
TMBQ (%)
Conversion
of TMP
(%)
performance with addition of
MgCl2·6H2O and [Bmim]Cl/
[Bmim]BF4
Control
13.5
9.5
8
8.5
8
92.5
93.4
96.7
94.7
94.3
100
100
100
100
100
1b
2c
3d
4e
aTemperature of 90 °C and stirring speed of 700 r/min
b2 g of MgCl2·6H2O, 0.5 g of [Bmim]Cl
c4 g of MgCl2·6H2O, 0.5 g of [Bmim]Cl
d2 g of MgCl2·6H2O, 0.5 g of [Bmim]BF4
e4 g of MgCl2·6H2O, 0.5 g of [Bmim]BF4
1 3

The efcient catalytic oxidation of 2,3,6‑trimethylphenol…
Fig. 1 The infuence of reaction
temperature on yield and reac-
tion time
hindered, which leads to the low selectivity of TMBQ. Therefore, 90 °C is the opti-
mal temperature for the reaction.
Infuence of stirring speed
The interfacial area between aqueous and organic phase as well as the air and liq-
uid phase is crucial in the heterogeneous catalytic reaction. Therefore, the interfacial
area has been tuned through the change of stirring speed. Figure 2 shows that the
stirring speed has a nonnegligible efect on the reaction time and yield. With the
increase in stirring speed from 500 to 800 r/min, the reaction time was signifcantly
shortened, and the yield of TMBQ was signifcantly increased, which indicated that
the increase in stirring speed would signifcantly increase the mass transfer rate
of the gas–liquid two-phase reaction system. The contact of gas and liquid phase
increases with the increase of rotating speed, and the liquid is more easily dispersed
into tiny droplets to react. However, the high rotational speed of 800 r/min will bring
instability to the whole reaction system. In addition, high stirring speed leads to
severe mechanical wear and energy consumption, but the yield of TMBQ almost
does not increase. Therefore, 700 r/min is considered as the optimal stirring speed.
Fig. 2 The infuence of stirring
speed on yield and reaction time
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T. Zhang et al.
Research on reaction kinetics
After the above exploration, the optimal reaction condition as follow: reaction tem-
perature of 90 °C, stirring speed of 700 r/min, original catalyst Y was added with 4 g
of MgCl2·6H2O and 0.5 g of [Bmim]Cl and the pressure of reaction is one atmos-
phere pressure. The conversion of TMP is 100% and the yield of TMBQ is 96.7%,
1
which has been verifed with the NMR spectra as seen in Fig. 3. The H spectrum
shows that the peaks of byproduct, 2,2′,3,3′,5,5′-hexamethyl-4,4′-diphenol, are much
weaker compared with the peak of TMBQ. The ratio of the sum of the intensity of
H in 2,2′,3,3′,5,5′-hexamethyl-4,4′-diphenol to that of H in TMBQ is roughly 6%,
verifying that the percentage of 2,2′,3,3′,5,5′-hexamethyl-4,4′-diphenol is almost
3% (the ratio of H atoms is 22:10). The peaks of byproduct in the 13C spectrum
are too weak to be observed clearly. The kinetic of the reaction is researched under
the optimal reaction condition. The relationship of the TMP conversion and TMBQ
selectivity vs reaction time is shown in Fig. 4. Only 14% TMBQ is obtained at the
reaction time of 1 h. As the reaction time increases, the conversion gets increased
to 96.7% at 7.5 h. The selectivity also gets increased. The curves indicate that the
intermediate product, is generated at the beginning and converts to the aim product,
TMBQ as the reaction goes on.
Recycle of catalyst
In order to reduce the production cost, the catalyst needs reuse. The catalytic activity
and stability were checked in the recycle trials four times. The catalyst was separated
from the organic phase and reused under the optimum condition. The recycled cata-
lytic performance has been shown in Table 4. The conversion keeps 100% after four
cycles and the selectivity keeps around 95%. Besides, the reaction time does not get
prolonged. It proves that composite catalyst has a stable catalytic activity after suc-
cessive cycling.
The possible mechanism of reaction
The catalytic oxidation mechanism of TMP over the composite catalyst of FeCl3,
CuCl2 and MgCl2 was described in Scheme 3, consistent with previous reports [8,
13]. Fe3+ and Cu2+ could oxidize TMP to TMP radical to trigger the following reac-
tion. Fe3+ and Cu2+ have similar function and therefore, Fe3+ was used to present
in the scheme. Mg2+ shows a synergistic efect. In the frst step, TMP was active
to TMP radical by Fe3+ or Cu2+, which then have three possible reaction routes. In
route (1), Fe3+ or Cu2+ activate O2 molecules to form the product TMBQ and water.
In the second route, two TMP radicals react to one form 2,2′,3,3′,5,5′-hexamethyl-
4,4′-diphenol molecule, the by product. In the third route, TMP radical react with
Cl− to form hydrogen radical and the intermediate product, TMPCl, which react
with O2 in the presence of Fe2+ to form the product TMBQ. During the whole pro-
cess, the ionic liquid does not work as a catalyst because the ionic liquid alone has
1 3

The efcient catalytic oxidation of 2,3,6‑trimethylphenol…
1
Fig. 3 A H NMR spectrum of TMBQ with byproduct (400 MHz, CDCl3). TMBQ δ 6.54 (s, 1H), 2.02
(s, 9H), 2,2′,3,3′,5,5′-hexamethyl-4,4′-diphenol δ 6.66–6.77 (t, 3H), 2.18–2.24 (m, 15H). B 13C NMR
spectrum of TMBQ with byproduct (400 MHz, CDCl3). TMBQ δc 188.16–187.46 (d, 2C) 133.27 (s, 1C),
140.72 (s, 2C), 145.23 (s, 1C), 15.75 (s, 1C) 11.93–12.31 (m, 2C) 2,2′,3,3′,5,5′-hexamethyl-4,4′-diphenol
δc 11.93–12.31 (m, 2c), 15.75–16.87(m, 3C), 123.42–144.24 (m, 11C), 109.88. (s, 1C)
1 3

T. Zhang et al.
Fig. 4 The reaction kinetics of
the synthesis of TMBQ
Table 4 The catalytic
Catalysta
Reaction time Selectivity of
Conversion
of TMP
(%)
performance of recycled catalyst
(h)
TMBQ (%)
Fresh
7.5
7.5
8
8
7.5
96.7
95.7
95.0
95.1
94.7
100
100
100
100
100
First reuse
Second reuse
Third reuse
Fourth reuse
aTemperature of 90 °C; stirring speed 700 r/min;
4 g of
MgCl2·6H2O, 0.5 g of [Bmim]Cl
no catalytic performance. In the presence of [Bmim]Cl, the water phase and organic
phase gain miscibility, which are initially insoluble, leading to the sufcient con-
tact between inorganic ions, (Fe3+, Cu2+, Mg2+ and Cl−) and organics (TMP, TMP
radical·and TMPCl).
Conclusion
The catalytic oxidation of TMP to synthesize TMBQ with the oxidant of air at one
atmosphere pressure was developed in this work and this is the frst report of this
reaction oxidized by air. After a series of investigations, 630 g of original catalyst Y
(CuCl2 and FeCl3) aqueous solution was added with 4 g of MgCl2·6H2O to achieve
optimal catalytic performance. 0.5 g of [Bmim]Cl is critical because it works as the
cocatalyst and can promote the miscibility of water phase and oil phase. The con-
version of TMP is 100% and the yield of TMBQ reaches 96.7% at the temperature
of 90 °C and the stirring speed of 700 r/min. The oxidation reaction undergoes a
free radical mechanism, among which, Cl− ion in the catalyst solution works as the
bridging role. The catalyst has shown good stability after recycling trials four times
with the yield around 95%. The usage of atmospheric air as the oxidant has notewor-
thy advantages than traditional O2 or H2O2. We believe this efective air oxidation
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The efcient catalytic oxidation of 2,3,6‑trimethylphenol…
Scheme 3 The possible catalytic oxidation mechanism of TMP to TMBQ
method developed in the research work will inspire the industrial production of
TMBQ and other related products.
Acknowledgements We gratefully acknowledge the support of Nantong Baisheng Company. The study
was supported by National Natural Science Foundation of China (21908161) and National Key R&D
Program of China (2017YFB0404701).
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