One-step highly selective oxidation of p-xylene to 4-hydroxymethylbenzoic acid over Cu-MOF catalysts under mild conditions

Article abstract of DOI:10.1016/j.mcat.2019.110542

p-Xylene, a cheap industrial raw material, is mainly used to synthesize terephthalic acid. However, p-xylene was oxidized rarely to other oxygen-containing derivatives. On the other hand, current methods for synthesis of 4-hydroxymethylenzoic acid suffer from multistep reactions, long reaction time, high temperature, high pressure, and lower selectivity. In this work, p-xylene was directly oxidized into 4-hydroxymethylbenzoic acid using Cu-MOF as the catalyst, acetonitrile as the solvent, and 30% H₂O₂ as the oxidant under mild conditions. Very high selectivity (99.2%) of 4-hydroxymethylbenzoic acid and good substrate conversion (85.5%) of p-xylene were achieved at 30 °C for 5 h. Fast hot catalyst filtration experiments proved that Cu-MOF acted as a heterogeneous catalyst. It can be reused three times without losing its activity. Under optimized conditions, the selectivity of 4-hydroxymethyl benzoic acid and the conversion of p-xylene were 97.6% and 84.8% even though the experiment was amplified 15-folds. The efficiency of H₂O₂ was also up to 92.0%. The reaction mechanism was proposed combined with the analysis of XRD, FT-IR and XPS. All data displayed that Cu-MOF shows great potential as a catalyst for highly selective oxidation of stable C–H to high value-added compounds containing two diverse C–O bands under mild conditions. It also opens a new way to use of p-xylene.

Full text of DOI:10.1016/j.mcat.2019.110542

MolecularCatalysis477(2019)110542
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.elsevier.com/locate/mcat
One-step highly selective oxidation of p-xylene to 4-hydroxymethylbenzoic
acid over Cu-MOF catalysts under mild conditions
Ying Lia,b, Mingzhu Wub, Daomei Chena, Liang Jianga, Jiao Hea, Zihao Luoa, Wei Wanga,
⁎
Jiaqiang Wanga,
a National Center for International Research on Photoelectric and Energy Materials, Yunnan Provincial Collaborative Innovation Center of Green Chemistry for Lignite
Energy, Yunnan Province Engineering Research Center of Photocatalytic Treatment of Industrial Wastewater, School of Energy, School of Chemical Sciences & Technology,
Yunnan University, Kunming 650091, PR China
b Chemical pollution control Chongqing Applied Technology Extension Center of Higher Vocational Colleges, Chongqing Industry Polytechnic College, Chongqing 401120,
PR China
A R T I C L E I N F O
A B S T R A C T
Keywords:
p-Xylene, a cheap industrial raw material, is mainly used to synthesize terephthalic acid. However, p-xylene was
oxidized rarely to other oxygen-containing derivatives. On the other hand, current methods for synthesis of 4-
hydroxymethylenzoic acid suffer from multistep reactions, long reaction time, high temperature, high pressure,
and lower selectivity. In this work, p-xylene was directly oxidized into 4-hydroxymethylbenzoic acid using Cu-
MOF as the catalyst, acetonitrile as the solvent, and 30% H2O2 as the oxidant under mild conditions. Very high
selectivity (99.2%) of 4-hydroxymethylbenzoic acid and good substrate conversion (85.5%) of p-xylene were
achieved at 30 °C for 5 h. Fast hot catalyst filtration experiments proved that Cu-MOF acted as a heterogeneous
catalyst. It can be reused three times without losing its activity. Under optimized conditions, the selectivity of 4-
hydroxymethyl benzoic acid and the conversion of p-xylene were 97.6% and 84.8% even though the experiment
was amplified 15-folds. The efficiency of H2O2 was also up to 92.0%. The reaction mechanism was proposed
combined with the analysis of XRD, FT-IR and XPS. All data displayed that Cu-MOF shows great potential as a
catalyst for highly selective oxidation of stable C–H to high value-added compounds containing two diverse C–O
bands under mild conditions. It also opens a new way to use of p-xylene.
p-xylene
4-Hydroxymethylbenzoic acid
Cu-MOF
Oxidation
1. Introduction
and medicine controlled release agent [5–8]. Moreover, HMBA, as a
linker, was also utilized to prepare sweetness sensor [9], dye-sensitized
Selective functionalization of unactivated C–H bond to C–O bond
represents an important and long-standing goal in chemistry. Achieving
regio- and chemoselective functionalization of different C–H bonds (sp2
and sp3) to C–X (X]C, O, and N) bonds also remains a tremendous
challenge in organic and organometallic chemistry, although these
transformations have broad potential in synthesis because CeH bonds
are ubiquitous in organic substances [1–3]. Especially, C–H bond is very
hard to oxide once more active C–X bonds exist in the substrate or the
reaction system. p-Xylene (PX), as a cheap industrial raw material, is
mainly used for synthesizing terephthalic acid (TPA) to prepare
polyester resins [4]. However, PX was oxidized rarely to other oxygen-
containing derivatives. 4-Hydroxymethylbenzoic acid (HMBA) has
widely drawn close attention because its’ hydroxyl and carboxyl groups
could be reacted with various functional groups. HMBA could be used
to synthesize drugs such as disease inhibitors, hydrophobic peptides,
solar cells [10], and photocatalyst [11]. However, HMBA were still
mainly synthesized by halogenation and hydrolysis of p-toluic acid
(Scheme 1(A)). Interestingly, Annen et al. reported that HMBA could be
prepared by catalytic aerobic dehydrogenation of 1,4-benzenedi-
methanol using rhodium(I) amido N-heterocyclic carbene complex as
the catalyst under alkaline conditions (Scheme 1(B)) [12]. Un-
fortunately, the yield of HMBA was very low (only 27%). Moreover,
these methods always need critical conditions, such as, multistep re-
actions, high temperature, high pressure, and long time. Moreover, the
selectivity of product is poor, which results in large amounts of un-
manageable wastes. As far as we know, investigation has been hardly
conducted in one-step synthesis of HMBA by liquid-phase catalytic
oxidation of PX Since hydroxymethyl group is more easily oxidized than
methyl group. Recently, HMBA was synthesized by the oxidation PX
using xylene monooxygenase as the catalyst (Scheme 1(C)) [13].
⁎ Corresponding author.
E-mail address: jqwang@ynu.edu.cn (J. Wang).
https://doi.org/10.1016/j.mcat.2019.110542
Received 22 January 2019; Received in revised form 14 June 2019; Accepted 31 July 2019
Availableonline07August2019
2468-8231/©2019ElsevierB.V.Allrightsreserved.

Y. Li, et al.
MolecularCatalysis477(2019)110542
Scheme 1. Synthesis methods of HMBA.
However, the application of this method was limited by a large number
of by-products (4-methylbenzylalcohol, p-tolualdehyde, and p-toluic
acid), the longer reaction time, and the lower yield. It is, therefore, of
great practical interest to develop a simple and efficient process for the
production of HMBA using PX as cheap raw material.
on the production of HMBA in this way as we know.
2. Experimental section
2.1. Synthesis of Cu-MOF
Metal-organic frameworks (MOFs), a type of zeolite-like crystalline
porous materials, have been extensively exploited in applications for
gas storage, separation and biomimetic catalysis because of their ex-
tremely large surface areas, wide variety of shapes and porosity, and
mimic enzymatic activities [14,15]. Especially, the use of MOFs as
heterogeneous catalysts is of interests due to possible advantages such
as ease of separation, efficient recycling, and minimization of trace
metal in products, and improved handling and process control [16–18].
Due to high selectivity and mild conditions, MOFs have been used as
selective oxidation catalysts such as epoxide of alkenes, oxidations of
(cyclo)alkanes and alcohols [16,18,19]. However, selective oxidations
for C–H bonds (sp and sp3) of alkylbenzenes to form simultaneously
diverse C–H bonds over MOFs were scarcely studied under fairly mild
conditions. Recently, we reported one-step preparation for 2, 5-dihy-
droxyterephathalic acid (H4DHT) by the hydroxylation of sp C–H bond
and the oxidation of sp3 C–H oxidation of PX using M-MCM-41 in mixed
solvents [20]. We found that meso-materials could be used for the se-
lective oxidation-functionalization of alkylbenzenes to synthesize high
value chemicals and the preparation of o-hydroxybenzoic acid deriva-
tives by non-Kolbe-Schmitt Process. Herein, we presented a simple and
efficient preparation for HMBA by one-step selective oxidation two
methyl groups of PX to hydroxymethyl and carboxyl using Cu-MOF as
the catalyst under mild conditions (Scheme 1(D)). This is the first report
Cu-MOF was synthesized via a hydrothermal method according to
Loiseau’s previous report [21]. In a typical synthesis, 5.0 g (24 mM)
benzene-1,3,5-tricarboxylic acid and 10.0 g (43 mM) copper (II) nitrate
hemipentahydrate were dissolved in 250 mL of solvent consisting of
equal parts N, N-dimethylformamide, ethanol and deionized water. The
solution was filled in a 1.0 L wide mouth glass jar and heated at 90 °C
for 20 h. After cooling, the product in the solution was filtered off to
remover excessive reactants, washed with DMF and immersed in di-
chloromethane for 3 day. The fresh dichloromethane was replenished
three times and removed under vacuum at 170 °C. The pure Cu-MOF
was obtained. Characterization of Cu-MOF, including before reaction
and after reaction, sees in the Supplementary Material.
2.2. General procedure for the oxidation reaction
All oxidation reactions of PX were performed in YuHua Parallel
Reactor (PPS-2510, five parallel reactions) equipped with magnetic
stirrer, super constant temperature and thermometer. A typical reaction
was as follows: PX (1.0 mL, 8.1 mmol), Cu-MOF (30.0 mg), acetonitrile
(10.0 mL), and 30% H2O2 (3.0 mL) was successively added into the
flask. The mixture was stirred at 30 °C for 5 h, cooled to room tem-
perature and filtered.
2

Y. Li, et al.
MolecularCatalysis477(2019)110542
Fig. 1. The effect of reaction temperature for the selective oxidation of PX
(Reaction conditions: PX, 1.0 mL (8.1 mmol); acetonitrile, 10.0 mL; H2O2
(30%), 1.0 mL; Cu-MOF, 20.0 mg; reaction time, 5 h).
2.3. Analyses of reaction products
Products were analyzed by a Purkinje General HPLC liquid chro-
matograph (LC-600) equipped with a UV detector and a C-18 column
(250 mm × 4.6 mm ×10 μm). 0.1% acetic acid in pure water (A) and
methanol (B) were of the mobile phase, and the flow rate was con-
trolled 0.85 mL/min. The HPLC program was as follows: 0–8 min, 65%
A; 8–14, 65–35% A; 14–40, 35% A; 40–46, 35–15% A; 46–60, 15% A.
The other parameters were 30 °C (column temperature), 235 nm (UV
detector), 61 min (stop time), and 20 μL (sample size).
3. Results and discussion
3.1. Effect of reaction temperatures
Considering the catalytic activity of Cu-MOF affected by reaction
temperature, oxidations of PX (1.0 mL) at different reaction tempera-
tures were firstly investigated using 1.0 mL 30% H2O2 as the oxidant
(Fig. 1). Obviously, both the conversion of PX (13.1%) and the se-
lectivity of HMBA (33.4%) were quite unsatisfactory if the oxidation
reaction could be operated at 70 °C. It was found that there were lots of
TPA, H4DHT and p-benzoquinone-2,5-dicarboxylic acid (BQDCA) in the
reaction system, coming possibly from the over-oxidation of HMBA
(Scheme 2). Meanwhile, Cu ion and 1,3,5-benzenetricarboxylic acid
were detected in the liquid phase by ICP-AES and HPLC, indicating Cu-
MOF collapsed and/or dissociated at elevated temperature. The co-ef-
fect of free copper ions and higher temperature resulted possibly in the
over-oxidation of HMBA and accelerated the decomposition of H2O2.
Simultaneously, under the catalysis of free copper ions, HMBA, TPA,
and H4DHT were easy oxidized more than PX, causing that the con-
version of PX was reduced. To improve the selective conversion of the
substrate to the desired product, the reaction temperature was reduced
from 70 °C to 30 °C. HMBA was increased consumedly and other oxides
Fig. 2. The effect of the selectivity oxidation of PX to HMPA (Reaction condi-
tions: PX, 1.0 mL (8.1 mmol); acetonitrile, 10.0 mL; H2O2 (30%), 1.0 mL; Cu-
MOF, 20.0 mg; reaction temperature ((A) 30 °C and (B) 70 °C); reaction time,
5 h).
(TPA, H4DHT and BQDCA) were deduced sharply with reducing reac-
tion temperature. At 30 °C, the selectivity of HMBA and the conversion
of PX were reached 99.3% and 28.6%, respectively. Meanwhile, the
conversion of PX displayed the trend of increase first and then decline.
Maximum conversion rate (34.0%) occurred at 50 °C. All data suggested
that the lower temperature was favourable for the synthesis of HMBA
by the one-step oxidation of P X .
3.2. Influence of reaction time
To further reveal the effect of temperatures (30 °C and 70 °C), the
oxidation reaction was investigated under various reaction times
(Fig. 2). From Fig. 2(A), it was found that the selective conversion of PX
was increased with increasing the reaction time at 30 °C. Furthermore,
by-products, including p-methyl benzyl alcohol and p-toluic acid, were
reduced during the extended reaction time. After 5 h, the selectivity of
HMBA and total amount of by-products was 99.3% and only 0.7%,
respectively. Except for PX and HMBA, there was a small amount of p-
methyl benzyl alcohol and p-toluic acid in the reaction system. PTA,
H4DHT, and BQDCA were not detected, stating clearly that HMBA was
not over-oxidized under this condition. The results also indicated Cu-
MOF didn’t collapse and/or dissociate at lower temperature. As seen
Scheme 2. The over-oxidation pathway of HMBA.
3

Y. Li, et al.
MolecularCatalysis477(2019)110542
Scheme 3. The oxidation pathway of PX under different reaction temperature.
from Fig. 2(B), it was could see that the conversion of PX was very low
(about 13.1%) although the reaction time was prolonged to 5 h. In
contrast to the selectivity of HMBA reduced dramatically, by-products
were increased sharply with increasing the reaction time. Unlike low
temperature (30 °C), main by-products were PTA, H4DHT, and BQDCA,
coming from the over-oxidized HMBA. All facts proved that the oxi-
dation pathways were different at various temperatures (Scheme 3(A)
and (B)). At lower temperature (Scheme 3(A)), PX was firstly oxidized
to p-methyl benzyl alcohol and benzyl alcohol coordination complexes
which came possibly from p-methyl benzyl alcohol coordinated with
Cu-MOF. And then, these compounds were converted to p-toluic acid
coordination complexes, reacting with peroxide to produce HMBA. At
higher temperature (Scheme 3(B)), however, p-toluic acid did not co-
ordinated with the catalyst because most of Cu-MOF were decomposed
to 1,3,5-benzenetricarboxylic acid and Cu(II). So, p-toluic acid was
converted catalytically by Cu (II) to HMBA and TPA [4,22], which were
further oxidized to H4DHT and BQDCA.
it decreased sharply in the excess of H2O2 (> 3.0 mL). Under the action
of various dosages of H2O2, types and quantities of by-products were
very different. There was only p-toluic acid was detected when the
dosage of H2O2 was less than 3.0 mL. But, TPA and H4DHT were ap-
peared because of the over-oxidation of HMBA only if more H2O2
(> 3.0 mL) was used in the reaction system. Based on our previous
calculation method [21], the efficiency of H2O2 decreased from 93.0%
to 63.0% when its dosage increased from 1.0 mL to 5.0 mL (Fig. 3).
Nevertheless, the efficiency of H2O2 was higher than 85.0% once its
amount was lower than 3.0 mL. All data showed that the selective of PX
was the following reaction path under such conditions (Scheme 4). PX
was firstly oxidized to p-toluic acid under the interaction of Cu-MOF
and H2O2. The methyl of p-toluic acid was further hydroxylated by
H2O2 to obtain HMBA (Scheme 4(A)). Due to the hydroxymethyl of
HMBA oxidized more than the methyl of p-toluic acid, HMBA was
converted to TPA under the action of a large amount of H2O2 (Scheme
4(B)). The ortho-position C–H bond of the carboxyl group of TPA was
ultimately hydroxylated to H4DHT under the action of Cu-catalyst
(Scheme 4(B)).
3.3. Influence of amounts of H2O2
3.4. Effect of the amount of Cu-MOF
To optimize reaction conditions, the influence of amounts of H2O2
(30%) was examined using Cu-MOF as the catalyst and acetonitrile as
the solvent under 30 °C for 5 h (Fig. 3). The conversion of PX was in-
creased with increasing amount of H2O2. More than 86.1% PX was
converted once 5.0 mL H2O2 was added into the reaction system.
However, the increase rate was very weak if the amount of H2O2 was
exceeded 3.0 mL. Satisfactorily, the selectivity of HMBA still had 96.4%
as long as the dosage of H2O2 would not be more than 3.0 ml, although
As an important factor, the effect of the amount of Cu-MOF for the
selective conversion of PX to HMBA was investigate at 30 °C for 5 h
using PX (1.0 mL) as the substrate, acetonitrile (10.0 mL) as the solvent,
and 30% H2O2 (3.0 mL) as the oxidant. From Fig. 4, it was found that
the appropriate amount of Cu-MOF would be beneficial to oxidize se-
lectively PX to HMBA. The amount of catalyst was too low to favour the
conversion of PX, although the selectivity of HMBA was satisfactory.
Moreover, the high amount of Cu-MOF was not conducive to convert
selectively to form desired product. The conversion of PX and the se-
lectivity of HMBA were respectively 82.2% and 97.0% when
30.0 mg Cu-MOF was used. Simultaneously, the selectivity of by-pro-
ducts, p-toluic acid, was only 3.0%. However, once amounts of the
catalyst were of more than 30.0 mg, PTA was also appeared in the re-
action system.
3.5. Effect of solvents
Due to the selective oxidation affected importantly by types and
amount of solvents, the solvent effect was discussed. Amounts of acet-
onitrile were first investigated for the selective synthesis of HMBA using
PX (1.0 mL) as the substrate, Cu-MOF (30.0 mg) as the catalyst, and
30% H2O2 (3.0 mL) as the oxidant at 30 °C for 5 h (Fig. 5). Although
there was no significant change in the conversion of PX and the se-
lectivity of HMBA, more suitable dosages of acetonitrile were 20.0 mL.
Under this condition, 85.8% PX was converted and 99.2% HMBA was
obtained in the reaction system. Moreover, p-toluic acid and p-methyl
benzyl alcohol were main by-products under low and high dosages of
Fig. 3. The effect of amounts of H2O2 (Reaction conditions: PX, 1.0 mL
(8.1 mmol); acetonitrile, 10.0 mL; Cu-MOF, 20.0 mg; reaction temperature,
30 °C; reaction time, 5 h).
4

Y. Li, et al.
MolecularCatalysis477(2019)110542
Scheme 4. The oxidation pathway of PX under various amounts of H2O2.
Table 1
The effect of the selective oxidation of PX under various solvents using Cu-MOF
as the catalyst.
a
b
c
Entry
Solvent
CPX (mol%)
SHMBA (mol%)
LC
1
2
water
3.2
59.1
99.2
78.9
65.3
70.2
44.5
50.6
61.8
49.5
98.1
N
N
N
N
N
Y
acetonitrile
methanol
ethanol
85.5
57.5
66.2
68.2
65.4
43.2
42.9
63.8
23.1
3
4
5
acetone
6
acetic acid
chloroform
diethyl ether
ethyl acetate
cyclohexane
7
N
N
8
9
Y (partial)
N
10
Reaction conditions: PX (1.0 mL), H2O2 (3.0 mL), Cu-MOF (30.0 mg), solvent
(20.0 mL), 30 °C, 5 h.
a
b
c
CPX: Conversion of PX.
Fig. 4. The effect of amounts of Cu-MOF (Reaction conditions: PX, 1.0 mL
(8.1 mmol); acetonitrile, 10.0 mL; reaction temperature, 30 °C; reaction time,
5 h).
SHMBA: Selectivity of HMBA.
LC: Leach of the catalyst (Cu ion in solution after 1 h was detected by ICP-
AES).
solvents were studied under the same conditions (Table 1). Although PX
was more or less converted to HMBA in these solvents, the conversion
and selectivity were various obviously. The order for the conversion of
PX was as follows: acetonitrile > acetone > ethanol > acetic
acid > ethyl acetate > methanol > chloroform > diethyl ether >
cyclohexane > water. Meanwhile, the order for the selectivity of
HMBA was as follows: acetonitrile > cyclohexane > methanol >
acetone > ethanol > diethyl ether > water > chloroform > ethyl
acetate > acetic acid. Furthermore, to investigate the leaching of ac-
tive sites of the catalyst, copper ion in all solutions reacted after 1 h was
detected by ICP-AES. Copper ions in most solvents were below the
detection limit indicating Cu-MOF was very stable. But, almost all
copper sites of Cu-MOF were leached into the solvent when acetic acid
was used. Simultaneously, partial copper ions were detected using ethyl
acetate as the solvent possible because ethyl acetate was hydrolyzed
catalytically to acetic acid and ethanol under the action of Cu-MOF.
Especially, the lower conversion of PX in water was partially because
the solubility of PX was so low that it interacted difficultly with oxidant
and catalyst. In addition, oxidation products of PX were more oxidized
easily than itself, resulting in PX was extremely difficult to be reacted
with oxidant. All data indicated that acetonitrile as the solvent was
suitable for the selective oxidation of PX to HMBA.
Fig. 5. The effect of amounts of acetonitrile (Reaction conditions: PX, 1.0 mL
(8.1 mmol); Cu-MOF, 30.0 mg; reaction temperature, 30 °C; reaction time, 5 h).
3.6. Test of the stability of Cu-MOF
acetonitrile, respectively. This was because various dosages of solvent
resulted in the difference of the unit concentration of H2O2.
To further understand the effect of other solvents, some common
To understand the thermal stability of Cu-MOF, hot filtration ex-
periments were operated after 2 h at 30 °C and 70 °C (Fig. 6). Obviously,
5

Y. Li, et al.
MolecularCatalysis477(2019)110542
under the optimized conditions. The catalytic activity, as shown
Table 2, remained nearly the same even after the fourth run. And the
efficiency of H2O2 was up to 93.0% even if Cu-MOF was used five times
(Table 2). Moreover, The detection result by ICP-AES revealed copper
ion was not leached from the heterogeneous material. The character-
ization of FT-IR, BET, XPS also displayed Cu-MOF was very stable be-
fore and after reaction (from Figure S1 to Figure S7). All results sug-
gested that Cu-MOF act as a heterogeneous catalyst in the reaction
system.
3.7. Investigation of the amplification of the reaction system
According to abovementioned experimental data, optimized condi-
tions were summarized as follows: 30% H2O2(V):PX(V) = 3:1, CH3CN
(V):PX(V) = 20:1, Cu-MOF(mg):PX(mL) = 30:1, 30 °C and 5 h. To in-
vestigate the possibility of industrial application, selective converting
PX to HMBA was amplified from 1-fold to 15-fold under optimized
conditions (Table 3). Although productivity reduced with the amplifi-
cation of the reaction system, experimental results were satisfactory
(Table 3, Entry 2–5). More than half of PX (65.3%) was oxidized se-
lectively HMBA (89.5%) after amplified 15-fold (Table 3, Entry 5), al-
though the efficiency of H2O2 has significantly decreased from 93.1% to
69.0%. In this reaction system, by-products were p-methyl benzyl al-
cohol, p-toluic acid and PTA. This might be due to the excessive addi-
tion of hydrogen peroxide. To further improve the yield of HMBA, more
solvent (450 mL) was added to impel PX convert selectively HMBA.
Consistent with prediction, the conversion of PX, the selectivity of
HMBA and the efficiency of H2O2 were up to 73.1%, 92.6% and 78.0%,
respectively (Table 3, Entry 6). Furthermore, to cut down target pro-
duct contact with oxidant, H2O2 was added three times (Table 3, Entry
7) and dropped (Table 3, Entry 8) to reduce its’ concentration in 300 mL
acetonitrile. The selective oxidation efficiency of PX was improved
further when 30% H2O2 was dropped in the reaction system (Table 3,
Entry 8). The selectivity of HMBA and the efficiency of H2O2 were al-
most the same with the unamplified experiment. The results indicated
that the catalytic efficiency of Cu-MOF was not significantly decreased.
Simultaneously, scale up experiment proved this method had potential
industrial application.
Fig. 6. The investigation of thermal stability of Cu-MOF (Reaction conditions:
PX, 1.0 mL (8.1 mmol); Cu-MOF, 30.0 mg; acetonitrile, 20.0 mL; reaction tem-
perature, 30 °C; reaction time, 5 h).
Table 2
Recycling experiment of Cu-MOF.
Entry
Run
CPX (mol%)a
SHMBA (mol%)b
E (mol%)c
1
2
3
4
5
fresh
85.5
85.6
85.5
85.5
85.4
99.2
99.1
99.3
99.2
99.3
93.1
93.2
93.1
93.1
93.0
1
2
3
4
Reaction conditions: PX (1.0 mL), H2O2 (3.0 mL), Cu-MOF (30.0 mg), acetoni-
trile (20.0 mL), 30 °C, 5 h.
a
b
c
CPX: Conversion of PX.
SHMBA: Selectivity of HMBA.
E: Efficiency of H2O2.
PX reaction with 30% H2O2 has been stopped at 30 °C once the catalyst
would be filtrated from the reaction medium. In contrast with lower
temperature (30 °C), the reaction continued after Cu-MOF filtrated at
70 °C. Experimental results proved again the conversion of PX affected
seriously by the reaction temperature.
Compared with other porous materials [23,24], Cu-MOF displayed
high performance in the selective functionalization of diverse C–H
bonds of PX to C–O bonds. Either one methyl was oxidized selectively
or two methyl groups were converted to same C–O group when Au-Pd/
MIL-101 [23] and Au-Pd/C [24] were used as catalysts. Simultaneously,
the lower selective conversion of PX was still existed although higher
To further verify the stability of the catalyst at 30 °C, recycle tests of
Cu-MOF was studied during the selective conversion of PX to HMBA
Table 3
Scale-up experiment of Cu-MOF.
CH3CNb (mL)
Cu-MOFc (mg)
CPX (mol%)
SHMBA (mol%)
Ef (mol%)
a
d
e
Entry
Fold
PX (mL)
H2O2 (mL)
1
–
1.0
3.0
20.0
30.0
85.5
85.3
82.9
75.7
65.3
73.1
77.7
84.8
99.2
98.9
96.4
93.1
89.5
92.6
94.2
97.6
93.1
93.0
90.0
81.0
69.0
78.0
84.0
92.0
2
1
2.0
6.0
40.0
60.0
3
5
5.0
15.0
30.0
45.0
45.0
45.0
45.0
100.0
200.0
300.0
450.0
300.0
300.0
150.0
300.0
450.0
450.0
450.0
450.0
4
10
15
15
15
15
10.0
15.0
15.0
15.0
15.0
5
6g
7h
8i
Reaction conditions: reaction temperature, 30 °C; reaction time, 5 h.
a
b
c
d
e
f
g
h
V(H2O2):V(PX) = 3:1.
V(CH3CN):V(PX) = 20:1.
M(Cu-MOF, mg):V(PX, mL) = 30:1.
CPX: Conversion of PX.
SHMBA: Selectivity of HMBA.
E: Efficiency of H2O2.
V(CH3CN):V(PX) = 30:1.
H2O2 was added in the three time (15.0 mL/time, 0 h, 2 h and 4 h).
i
H2O2 was dropped.
6

Y. Li, et al.
MolecularCatalysis477(2019)110542
Table 4
Compared with references during the selective functionalization of P X .
Entry
Catalyst
Temperature (oC)
Time (h)
CPX (mol%)a
Smp (mol%)b
Ref.
1
2
3
Cu-MOF
30
5
85.5
40.2
6.8
99.2c
65.0d
67.9e
——
28
Au-Pd/MIL-101
Au-Pd/C
120
160
48
48
29
a
b
c
d
e
CPX: Conversion of PX.
Smp: Selectivity of main product.
Selectivity of HMBA.
Selectivity of 4′-methylbenzyl 4-methylbenzoate.
Selectivity of C-C products/Esters.
temperature and longer time were given (Table 4, entry 2 and 3).
Furthermore, in addition to p-toluic acid, among of by-products were p-
toluyl alcohol and p-tolualdehyde in these reaction systems. These data
proved Cu-MOF displayed excellently selective conversion of in-
activated C–H bond to C–O bond under mild conditions.
XRDs (Figure S2) discovered the crystalline form of Cu-MOF was pur-
ified after reaction because of interaction with solvent and the catalyst.
This conjecture was verified by surface area, pore volume, and pore size
(Table S1). Adsorption and desorption isothermal curves (Figure S3)
displayed the similar structure of Cu-MOF at before and after reaction.
Meanwhile, the unchanged structure of Cu-MOF was also proved by
XPSs of Cu-MOF (from Figure S4 to Figure S7). All characterizations
indicated Cu-MOF was a heterogeneous catalyst and was not changed
during the selective oxidation of PX to HMBA.
3.8. Comparison of physicochemical properties before and after reaction
To discover the unparalleled properties, the structure of Cu-MOF
before and after reaction was compared by FT-IR, XRD, BET, and XPS
(from Figure S1 to Figure S7, Table S1). Spectrums of FT-IR were
consistently whether before reaction or after reaction (Figure S1), in-
dicating the structure and ligand of Cu-MOF was almost unchanged.
3.9. Proposed reaction mechanism
According to the experimental data and characterizations of Cu-
Scheme 5. The proposed mechanism.
7

Y. Li, et al.
MolecularCatalysis477(2019)110542
MOF, the proposed mechanism was as follows. On the one hand, LnCu
(Cu-MOF, Ln = benzene-1,3,5-tricarboxylic acid) coordinated easily
with hydrogen peroxide to generate Cu-O-O-H complex with functional
ligand (Scheme 5(1)). LnCu-O-O-H was very important as active in-
termediates in biological oxygenases such as dopamine β-hydroxylase
(DβH) [25,26]. LnCu-O-O-H reacted with the C–H bond of PX by hy-
drogen abstract to form water and Cu(II) alkoxide (Scheme 5(2)) [27].
One the other hand, homolytic cleavage of hydrogen peroxide brought
under the action LnCu (Cu-MOF) to produce hydroxyl radical (Scheme
5(3)). The hydroxyl radical would be abstract one hydrogen of methyl
of Cu(II) alkoxide to water and Cu(II) alkoxide radical (Scheme 5(4))
[28–30]. Cu(II) alkoxide radical reacted continuously with hydroxyl
radical until the carbonyl group was formed (Scheme 5(5)-(10)). Fi-
nally, acid derivative of Cu(II) alkoxide was acidolysed to obtain HMBA
and LnCu (Cu-MOF) [31].
[4] R.A. Tomas, J.C. Bordado, J.F. Gomes, p-Xylene oxidation to terephthalic acid: a
literature review oriented toward process optimization and development, Chem.
Rev. 113 (2013) 7421–7469.
[5] J. Bussenius, C.M. Blazey, N. Aay, N.K. Anand, A. Arcalas, T. Baik, O.J. Bowles,
C.A. Buhr, S. Costanzo, J.K. Curtis, S.C. Defina, L. Dubenko, T.S. Heuer, P. Huang,
C. Jaeger, A. Joshi, A.R. Kennedy, A.I. Kim, K. Lara, J. Lee, J. Li, J.C. Lougheed,
S. Ma, S. Malek, J.C. Manalo, J.F. Martini, G. Mcgrath, M. Nicoll, J.M. Nuss,
M. Pack, C.J. Peto, T.H. Tsang, L. Wang, S.W. Womble, M. Yakes, W. Zhang,
K.D. Rice, Discovery of XL888: a novel tropane-derived small molecule inhibitor of
HSP90, Bioorg. Med. Chem. Lett. 22 (2012) 5396–5404.
[6] J.H. Lee, Y. Yao, A. Mahendran, L. Ngo, G. Venta-Perez, M.L. Choy, R. Breslow,
P.A. Marks, Creation of a histone deacetylase 6 inhibitor and its biological effects,
PNAS 112 (2015) E5899.
[7] C.C. Seaton, A. Parkin, Making benzamide cocrystals with benzoic acids: The in-
fluence of chemical structure, Cryst. Growth Des. 11 (2011) 1502–1511.
[8] S. Imm, S. Bahn, M. Zhang, L. Neubert, H. Neumann, F. Klasovsky, J. Pfeffer,
T. Haas, M. Beller, Improved ruthenium-catalyzed amination of alcohols with am-
monia: synthesis of diamines and amino esters, Angew. Chem. Int. Ed. 50 (2011)
7599–7603.
[9] K. Toyota, H. Cui, K. Abe, M. Habara, K. Toko, H. Ikezaki, Sweetness sensor with
lipid/polymer membranes: sweet-responsive substances, Sens. Mater. 23 (2011)
465–474.
4. Conclusions
[10] P. Rajakumar, K. Visalakshi, S. Ganesan, P. Maruthamuthu, S.A. Suthanthiraraj,
Pyreno-chalcone dendrimers as an additive in the redox couple of dye-sensitized
solar cells, J. Mater. Sci. 47 (2011) 1811–1818.
Selective oxidation of p-xylene to 4-hydroxymethylbenzoic acid was
studied. Reaction temperature, amounts of H2O2, types and amounts of
solvents, amounts and thermal stability and amounts of catalyst were in-
vestigated. The conversion of p-xylene and the selectivity of 4-hydro-
xymethylbenzoic acid were respectively 85.5% and 99.2% using Cu-MOF
as the catalyst and acetonitrile as the solvent at 30 ° C for 5 h, indicating
Cu-MOF was a high performance oxidation catalyst under mild conditions.
Thermal filtration experiment, recycle tests, and physical characterizations
displayed Cu-MOF was very stable under given reaction conditions. Under
optimized conditions, the selectivity of 4-hydroxymethylbenzoic acid
(97.6%) and the conversion of p-xylene (84.8%) were even though the
experiment was amplified 15-folds. Simultaneously, the efficiency of
H2O2 was up to 92.0%. All data displayed that Cu-MOF shows great po-
tential as a catalyst for highly selective oxidation of stable C–H to high
value-added compounds containing two diverse C–O bands under mild
conditions. It also opens a new way to use of p-xylene.
[11] M.B. Andrews, C.L. Cahill, Uranyl hybrid material derived from in situ ligand
synthesis: formation, structure, and an unusual phase transformation, Angew.
Chem. Int. Ed. 51 (2012) 6631–6634.
[12] S. Annen, T. Zweifel, F. Ricatto, H. Grützmacher, Catalytic aerobic dehydrogenative
coupling of primary alcohols and water to acids promoted by a rhodium (I) amido
N-heterocyclic carbene complex, ChemCatChem 2 (2010) 1286–1295.
[13] M. Brumucci, V. Nagarajan, S. Thomas, Microbial production of terephthalic acid
and isophthalic acid, U.S. Patent No. 6,187,569. 13 Feb. 2001.
[14] H.C. Zhou, J.R. Long, O.M. Yaghi, Introduction to metal–organic frameworks,
Chem. Rev. 112 (2012) 673–674.
[15] Y. Chen, S. Ma, Biomimetic catalysis of metal–organic frameworks, Dalton Trans. 45
(2016) 9744–9753.
[16] A. Dhakshinamoorthy, M. Alvaro, H. Garcia, Metal–organic frameworks as het-
erogeneous catalysts for oxidation reactions, Catal. Sci. Technol. 1 (2011) 856–867.
[17] A.H. Chughtai, N. Ahmad, H.A. Younus, A. Laypkov, F. Verpoort, Metal–organic
frameworks: versatile heterogeneous catalysts for efficient catalytic organic trans-
formations, Chem. Soc. Rev. 44 (2015) 6804–6849.
[18] G. Zi, Z. Yan, Y. Wang, Y. Chen, Y. Guo, F. Yuan, W. Gao, Y. Wang, J. Wang,
Catalytic hydrothermal conversion of carboxymethyl cellulose to value-added
chemicals over metal–organic framework MIL-53 (Al), Carbohydr. Polym. 115
(2015) 146–151.
Acknowledgements
[19] A. Cdhakshinamoorthy, A.M. Asiri, H. Garcia, Metal–organic frameworks as cata-
lysts for oxidation reactions, Chem. Eur. J. 22 (2016) 8012–8024.
[20] O.A. Kholdeeva, Liquid-phase selective oxidation catalysis with metal organic fra-
meworks, Catal. Today 278 (2016) 22–29.
The work was supported by National Natural Science Foundation of
China (Project 21573193, 21603188 and 21773204). The authors also
thank the Key Projects for Research and Development of Yunnan Province
(2018BA065), the Scientific Research Fund of Department of Yunnan
Education (Project 2016CYH04 and 2017ZZX223), < GS4 > Yunnan
[21] Y. Li, D. Duan, M. Wu, J. Li, Z. Yan, W. Wang, G. Zi, J. Wang, One-step synthesis of
2,5-dihydroxyterephthalic acid by the oxidation of p-xylene over M-MCM-41 (M=
Fe, Fe/Cu, Cu) catalysts, Chem. Eng. J. 306 (2016) 777–783.
[22] J. Fraga-Dubreuil, M. Poliakoff, Organic reactions in high-temperature and super-
critical water, Pure Appl. Chem. 78 (2006) 1971–1982.
[23] H. Liu, Y. Li, H. Jiang, C. Vargas, R. Luque, Significant promoting effects of Lewis
acidity on Au–Pd systems in the selective oxidation of aromatic hydrocarbons,
Chem. Commun. 48 (2012) 8431–8433.
Applied
Basic
Research
Projects < \GS4 > (< GN4 > 2016F-
D009 < \GN4 > , < GN4 > 2018FB013 < \GN4 >), the Program for
Innovation Team of Yunnan Province and Key Laboratory of Advanced
Materials for Wastewater Treatment of Kunming for financial support, New
technology promotion Program of Chongqing Municipal Education
Commission (GZTG201607), Yubei District science and technology program
of Chongqing (No. 201606), and scientific and technological innovation
team of Chongqing Industry Polytechnic College (GZY2017CXT02) for fi-
nancial support.
[24] L. Kesavan, R. Tiruvalam, M.H.A. Rahim, M.I. Saiman, D.I. Enache, R.L. Jenkins,
N. Dimitratos, J.A. Lopez-Sanchez, S.H. Taylor, D.W. Knight, C.J. Kiely,
G.J. Hutching, Solvent-free oxidation of primary carbon-hydrogen bonds in toluene
using Au-Pd alloy nanoparticles, Science 331 (2011) 195–199.
[25] T. Loiseau, C. Serre, C. Huguenard, G. Fink, F. Taulelle, M. Henry, T. Bataille,
G. Ferey, A rationale for the large breathing of the porous aluminum terephthalate
(mil-53) upon hydration, Chem. Eur. J. 10 (2004) 1373–1382.
[26] S. Yamaguchi, S. Nagatomo, T. Kitagawa, Y. Funahashi, T. Ozaw, K. Jitsukawa,
H. Masuda, Copper hydroperoxo species activated by hydrogen-bonding interaction
with its distal oxygen, Inorg. Chem. 42 (2003) 6868–6970.
[27] S. Gentil, D. Serre, C. Philouze, M. Holzinger, F. Thomas, A.L. Goff, Electrocatalytic
Appendix A. Supplementary data
O
2 reduction at a bio-inspired mononuclear copper phenolato complex immobilized
on a carbon nanotube electrode, Angew. Chem. Int. Ed. 55 (2016) 2517–2520.
[28] J.Y. Lee, R.L. Peterson, K. Ohkubo, I. Garcia-Bosch, R.A. Himes, J. Woertink,
C.D. Moore, E.I. Solomon, S. Fukuzumi, K.D. Karlin, Mechanistic insights into the
oxidation of substituted phenols via hydrogen atom abstraction by a cupric–su-
peroxo complex, J. Am. Chem. Soc. 136 (2014) 9925–9937.
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.mcat.2019.110542.
References
[29] Y. Wang, H. Liu, X. Zhang, Z. Zhang, D. Huang, Experimental and mechanistic in-
sights into copper (ii)–dioxygen catalyzed oxidative N-dealkylation of N-(2-pyr-
idylmethyl) phenylamine and its derivatives, Org. Biomol. Chem. 15 (2017)
9164–9168.
[1] G. Kamil, S. Dalibor, C-H bond functionalization in complex organic synthesis,
Science 312 (2006) 67–72.
[30] S. Kim, J.W. Ginsbach, J.Y. Lee, R.L. Peterson, J.J. Liu, M.A. Siegler, A.A. Sarjeant,
E.I. Solomon, K.D. Karlin, Amine oxidative N-dealkylation via cupric hydroperoxide
Cu-OOH homolytic cleavage followed by site-specific Fenton chemistry, J. Am.
Chem. Soc. 137 (2015) 2867–2874.
[2] A.R. Dick, K.L. Hull, M.S. Sanford, A highly selective catalytic method for the
oxidative functionalization of C-H bonds, J. Am. Chem. Soc. 126 (2004)
2300–2301.
[3] A.C. Lindhorst, S. Haslinger, F.E. Kühn, Molecular iron complexes as catalysts for
selective C–H bond oxygenation reactions, Chem. Commun. 51 (2015)
17193–17212.
[31] S. Marx, W. Kleist, A. Baiker, Synthesis, structural properties, and catalytic behavior
of Cu-BTC and mixed-linker Cu-BTC-PyDC in the oxidation of benzene derivatives,
J. Catal. 281 (2011) 76–87.
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