Sequential Connection of Mutually Exclusive Catalytic Reactions by a Method Controlling the Presence of an MOF Catalyst: One-Pot Oxidation of Alcohols to Carboxylic Acids

Article abstract of DOI:10.1021/acs.inorgchem.0c02809

A functionalized metal-organic framework (MOF) catalyst applied to the sequential one-pot oxidation of alcohols to carboxylic acids controls the presence of a heterogeneous catalyst. The conversion of alcohols to aldehydes was acquired through aerobic oxidation using a well-known amino-oxy radical-functionalized MOF. In the same flask, a simple filtration of the radical MOF with mild heating of the solution completely altered the reaction media, providing radical scavenger-free conditions suitable for the autoxidation of the aldehydes formed in the first step to carboxylic acids. The mutually exclusive radical-catalyzed aerobic oxidation (the first step with MOF) and radical-inhibited autoxidation (the second step without MOF) are sequentially achieved in a one-pot manner. Overall, we demonstrate a powerful and efficient method for the sequential oxidation of alcohols to carboxylic acids by employing a readily functionalizable heterogeneous MOF. In addition, our MOF in-and-out method can be utilized in an environmentally friendly way for the oxidation of alcohols to carboxylic acids of industrial and economic value with broad functional group tolerance, including 2,5-furandicarboxylic acid and 1,4-benzenedicarboxylic acid, with good yield and reusability. Furthermore, MOF-TEMPO, as an antioxidative stabilizer, prevents the undesired oxidation of aldehydes, and the perfect "recoverability"of such a reactive MOF requires a re-evaluation of the advantages of MOFs from heterogeneity in catalytic and related applications.

Full text of DOI:10.1021/acs.inorgchem.0c02809

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Sequential Connection of Mutually Exclusive Catalytic Reactions by
a Method Controlling the Presence of an MOF Catalyst: One-Pot
Oxidation of Alcohols to Carboxylic Acids
Seongwoo Kim,§ Ha-Eun Lee,§ Jong-Min Suh, Mi Hee Lim,* and Min Kim*
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ABSTRACT: A functionalized metal−organic framework (MOF) catalyst applied to the
sequential one-pot oxidation of alcohols to carboxylic acids controls the presence of a
heterogeneous catalyst. The conversion of alcohols to aldehydes was acquired through aerobic
oxidation using a well-known amino-oxy radical-functionalized MOF. In the same flask, a simple
filtration of the radical MOF with mild heating of the solution completely altered the reaction
media, providing radical scavenger-free conditions suitable for the autoxidation of the aldehydes
formed in the first step to carboxylic acids. The mutually exclusive radical-catalyzed aerobic
oxidation (the first step with MOF) and radical-inhibited autoxidation (the second step without
MOF) are sequentially achieved in a one-pot manner. Overall, we demonstrate a powerful and
efficient method for the sequential oxidation of alcohols to carboxylic acids by employing a readily
functionalizable heterogeneous MOF. In addition, our MOF in-and-out method can be utilized in
an environmentally friendly way for the oxidation of alcohols to carboxylic acids of industrial and
economic value with broad functional group tolerance, including 2,5-furandicarboxylic acid and
1,4-benzenedicarboxylic acid, with good yield and reusability. Furthermore, MOF-TEMPO, as an
antioxidative stabilizer, prevents the undesired oxidation of aldehydes, and the perfect “recoverability” of such a reactive MOF
requires a re-evaluation of the advantages of MOFs from heterogeneity in catalytic and related applications.
MOF-based heterogeneous catalysts, however, have been
developed using the chemoselectivity of organic transforma-
tions. In previous studies, the catalytic species for Knoevenagel
condensation did not impact the catalytic cycle of oxidation (the
first step), and the catalytic species and mechanisms of aerobic
oxidation have no effect on Knoevenagel condensation. At the
same time, the catalytic system for epoxidation and ring-opening
should not interfere with or damage the two reactions.
Therefore, the mutually exclusive two or more catalytic reactions
cannot be achieved by a single MOF even with multi-
functionalization.
To connect two incompatible organic reactions following a
mechanistic viewpoint, we focused on the excellent hetero-
geneity of MOFs with the ultimate tunability of organic ligands.
Although radical-catalyzed reactions and radical-inhibited
mechanisms cannot be connected or performed in a single
pore, the catalytic MOF platform provides the perfect control of
radicals (i.e., catalytically active species) via addition and
removal for each transformation by filtration or centrifugation
INTRODUCTION
■
Metal−organic frameworks (MOFs) are emerging organic−
inorganic hybrid and porous materials for catalytic applica-
tions.1−4 MOFs serve as an excellent platform for designing
heterogeneous catalysts by combining molecular functional
groups into solid-state materials because of their high porosity,
stability, and tunability, and these heterogeneous catalysts have
been utilized for a wide range of organic transformations.5−10
The metal cations or clusters on the node of MOFs could act as a
Lewis acid catalytic site for organic transformations. In addition,
the fine tunability of ligands allows the installation of active
catalytic species such as metal complexes or radical moieties on
the ligand struts of MOFs.9−13 Most importantly, a number of
catalytic species could be strategically introduced into a single
MOF through multifunctionalization or multivalent MOFs.14,15
The well-designed MOF-based catalysts and in-depth mecha-
nistic investigations have been reported to afford catalysts that
outcompete homogeneous catalysts under certain reactions.7
MOF-based heterogeneous catalysts with more than two
different catalytic sites could perform a sequential or a tandem
organic transformation in a single pore.14−25 For example, the
oxidation of alcohols to aldehydes and Knoevenagel con-
densation could be sequentially connected in a single MOF
catalyst,21 and the epoxidation of alkenes followed by epoxide
opening with various nucleophiles could be performed through a
domino reaction type (Scheme 1).23 The tandem reactions with
Received: September 21, 2020
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Scheme 1. MOF-Catalyzed Tandem or Sequential Reactions and the MOF in-and-out Method in the Present Study
(Scheme 1). In this case, the radical-catalyzed reaction as the
first step is performed, and then the reaction medium is changed
for autoxidation by removing the radical-functionalized MOFs.
While this MOF in-and-out method (i.e., MOF catalyst “in” for
the first step and MOF catalyst “out” for the second step) simply
applies to the reaction procedures, two mutually exclusive
transformations can sequentially occur for efficient synthesis. In
this work, for the first time, we report the MOF in-and-out
method that originated from the heterogeneity with fine-
tunability of MOFs and is not based on chemoselectivity, to the
best of our knowledge.
B
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We used the sequential one-pot oxidation reactions of
alcohols to carboxylic acids in a method controlling the presence
of MOF-TEMPO (TEMPO = (2,2,6,6-tetramethylpiperidin-1-
yl)oxyl) (the MOF in-and-out method). The MOF-catalyzed
aerobic oxidation of alcohols to corresponding aldehydes is well-
known chemistry and is widely studied. A variety of strategies
have been incorporated into MOFs to carry out aerobic
oxidation, and they could be generally categorized as amino-
oxy-radical-containing MOFs,26−32 metal-cation-incorporated
MOFs,33−38 and metal-nanoparticle-embedded MOFs.39−42 In
particular, a zirconium-based UiO series of MOFs (UiO =
University of Oslo) with TEMPO have been extensively studied
with respect to aerobic oxidation.30,31 Zhaung and co-workers
successfully developed an efficient aerobic oxidation of alcohols
to aldehydes with MOF-TEMPO in the UiO-68 platform in the
presence of O2, and the synergic effect between Zr nodes of
MOF and TEMPO was investigated.30
application of this study. Moreover, our MOF in-and-out
method was demonstrated to cover a wide range of substrates
producing products in relatively good yields as well as being
recycled for up to eight cycles (for the step with the MOF).
RESULTS AND DISCUSSION
■
Screening of Catalytic Conditions and Control Experi-
ments. We rationally selected a well-known, simple, stable
zirconium-based UiO-68-TEMPO (MOF-TEMPO, Scheme 2)
Scheme 2. Synthetic Scheme of MOF-TEMPO
Molecular dioxygen (O2) is commonly utilized as the final
oxidant for all the three types of MOF catalysts (Scheme 1), and
water is produced as the only byproduct. However, the oxidation
of alcohols to aldehydes has not been successful with most of the
functionalized MOFs. Until now, the overoxidation of aldehydes
to carboxylic acids by employing such MOF-based catalysts has
not been reported. This is because the second step in oxidation,
autoxidation, is inhibited by radicals such as TEMPO.43−46
Therefore, neither aerobic oxidation nor autoxidation can occur
sequentially from alcohols to carboxylic acids in the same flask or
in a single MOF pore. In the homogeneous system, the
dehydrogenation and oxidation processes have been developed
to convert alcohols to carboxylic acids with transition-metal
systems47−50 and metal-free systems.51−53 It should be noted
that the amino-oxy-radical-catalyzed aerobic oxidation of
alcohols to carboxylic acids through iron-catalyzed reactions
[the Fe(NO3)3/TEMPO system and TEMPO-consumption
process] and the electrochemical methods (with amine-
functionalized TEMPO) has been recently illustrated in the
case of homogeneous catalysis.54−62 Finally, a TEMPO-
functionalized polymer was also utilized for the oxidation of
alcohols to carboxylic acids in mechanochemical systems.63 This
polymer-based catalyst, however, is the combinatorial system
between TEMPO and another oxidant: Oxone. TEMPO is used
in the aerobic oxidation of alcohols to aldehydes followed by the
Oxone-catalyzed second oxidation to carboxylic acids. The
catalysis is not able to be recycled without refilling Oxone.
To achieve selective transformation from alcohols to
carboxylic acids using heterogeneous, well-known, TEMPO-
functionalized MOFs, our MOF in-and-out method was
thoroughly investigated via optimization and control experi-
ments. Research on the MOF-catalyzed oxidation of alcohols to
carboxylic acids has been sluggish, relative to that of other
available catalytic systems, due to multiple limitations, including
the incorporation of the produced carboxylic acids into the
structures of MOF catalysts,27 the difficulty of controlling the
selectivity,64,65 the inhibition of overoxidation by amino-oxy
radicals,26−32 the detachment of oxy species from MOFs
through N−O cleavage (by Fe catalysts),66,67 the accumulation
of salts in MOFs (by excess amounts of OCl sources),60−62 and
the narrow scope of aliphatic substrates.68,69 Indeed, we
confirmed the facile recoverability of the MOF used for this
study, which is a significant advantage of MOFs and has not
received as much attention as their reusability in the literature.
The deterrence of MOF-TEMPO to autoxidation was also
verified to efficiently stabilize benzaldehyde in air as a practical
as a TEMPO-functionalized MOF catalyst and tert-butyl nitrite
(TBN) to design our method for continuous two-step oxidation
processes from alcohols to carboxylic acids.30,31 The main
ligand, TPDC-TEMPO (TPDC = p-terphenyl-4,4″-dicarboxylic
acid), and MOF-TEMPO (from the reaction with ZrCl4) were
prepared by previously reported procedures with minor
modifications, as illustrated in Scheme 2.30,31 MOF-TEMPO
as the main MOF catalyst was obtained by isolating pale-pink
octahedral crystals. The structure of MOF-TEMPO was
confirmed by powder X-ray diffraction (PXRD) patterns (Figure
S1). The TEMPO functionality in MOF was characterized by
1H nuclear magnetic resonance (NMR) spectroscopy after acid
digestion (Figure S2). Finally, N2 adsorption/desorption
experiments were conducted to determine the porosity and
surface area of MOF-TEMPO (Figure S3). The BET
(Brunauer−Emmett−Teller) surface area was calculated to be
871 m2/g, and the pore size distribution analysis through the
NLDFT (nonlock density functional theory)70 model displayed
12 and 15 Å for the main contributions (Figure S3). Since the
TEMPO moiety connected to an amide group is quite large, the
surface area and the pore size were decreased, compared to those
of pristine UiO-68 (2143 m2/g for the BET surface area and 16.4
to 17.7 Å for the pore size).71,72
As the first step, the aerobic oxidation of benzyl alcohol (1a)
to benzaldehyde (2a) was first optimized through a combination
of MOF-TEMPO and TBN, as summarized in Table 1 (entries
1−3). No significant conversion of 1a to 2a was observed by
MOF-TEMPO or TBN alone in acetonitrile (CH3CN) under an
O2 atmosphere. When both MOF-TEMPO and TBN were
introduced into the reaction solution (entry 4), 1a was nearly
fully oxidized to 2a at room temperature within 2 h. Notably, in
the presence of MOF-TEMPO, the overoxidation of 2a to
benzoic acid (3a) was not indicated under any conditions, as
confirmed by TLC (thin-layer chromatography), GC (gas
chromatography), and 1H NMR spectroscopy (Table 1, entry 4
and Table S1, entry 5). It should be noted that 3a was not
produced in the previous study for the aerobic oxidation of 1a to
2a by elevating the temperature to 80 °C under the same
catalytic condition (UiO-68-TEMPO and TBN).30 As men-
tioned earlier, the optimized conditions involve two steps: (i) 2a
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a
Table 1. Optimization of the Reaction Conditions
Scheme 3. Control Experiments (I) to Identify the
a
Involvement of the Radical Species in the Second Step
c
conv (%)
b
b
entry MOF-TEMPO (5 mol %) TBN (20 mol %) 1a to 2a 2a to 3a
1
2
3
4
5
6
X
O
X
O
O
O
X
X
O
O
O
O
<1
<1
4
99
99
3
n.r.
n.r.
n.r.
n.r.
n.r.
97/96
d
e
f
a
Reaction conditions: 1a (0.5 mmol, 54 mg), MOF-TEMPO (0.025
mmol, 16 mg), TBN (0.1 mmol), and solvent (1 mL) were used. The
reaction was stirred under an O2 balloon at 25 °C for 2 h, followed by
the filtration of MOF-TEMPO and additional stirring under an O2
b
c
balloon at 80 °C for 10 h. O = used; X = not used. GC conversion;
d
e
n.r. = no reaction. No MOF-TEMPO filtration. After the filtration
of MOF-TEMPO, the reaction was stirred under an O2 balloon at 60
f
°C for 10 h. Isolated yield (%).
a
was first generated by performing the first step at 25 °C for 2 h;
(ii) after MOF-TEMPO was easily separated by centrifugation,
3a was acquired in the second step by heating the reaction
mixture to 80 °C. Interestingly, MOF-TEMPO was recovered
after oxidation of the alcohol to the aldehyde, and an
approximately quantitative amount of 3a was obtained (entry
6) via oxidation of 2a in the presence of O2 at 80 °C for 10 h. The
conversion of 2a to 3a was sensitive to the variation in the
reaction temperature (Table 1, entries 5 and 6 and Table S1,
entries 1−4). On the basis of the boiling point of CH3CN, 80 °C
was appropriate for autoxidation (Table 1, entry 6). The nature
of the solvent substantially influenced the outcome of the
autoxidation of the aldehyde to the carboxylic acid. For example,
when 1,2-dichloroethane (1,2-DCE) was used instead of
CH3CN, the conversion was lowered (83%; Table S1, entry
6). Additionally, other solvents such as ethyl acetate, toluene,
water, and 1,4-dioxane were not effective for the oxidation of 1a
to 2a, along with no formation of 3a (Table S1, entries 7−10). In
addition to the transformation of 2a to 3a, the autoxidation
reaction of 2a to 3a was significantly affected by the solvents
(Table S2, entries 4−8).
n.d., not detected.
Scheme 4. Control Experiments (II) to Determine If the
Alcohol and O2 Affect the Second Step
a
To identify the sequential oxidation better, a series of control
experiments were conducted, as shown in Scheme 3. The
presence of homogeneous or heterogeneous TEMPO species
notably suppressed the generation of carbonyl compound 3a
(Scheme 3a,c), implying that the autoxidation as the second step
was inhibited by an additional radical species or a solid catalyst in
solution. Furthermore, as depicted in Scheme 3d,e, the presence
of MOF-TEMPO was altered for direct comparison. First, when
the conversion of 1a to 2a was completed and the second step
was carried out by recovering MOF-TEMPO, a conversion rate
of 52% to 3a was formed after 4 h. Not surprisingly, upon
reintroduction of MOF-TEMPO into the reaction, the
conversion was stopped (after both 6 and 8 h, 51%). Again,
the formation of 3a was increased after 10, 12, and 14 h (72, 87,
and 96%, respectively) by removing MOF-TEMPO from the
reaction.
a
n.d., not detected.
1a can quench free radicals that are involved in autoxidation.73
Basically, the full conversion of alcohols to aldehydes is required
for the efficient second step. In addition, tert-butyl alcohol (t-
BuOH) generated as a byproduct of TBN, as shown in Scheme
4b, did not inhibit the radical reaction, as expected because it is a
tertiary alcohol.73 Finally, the requirement of O2 in the second
step was verified by conducting the reaction under an N2
atmosphere (Scheme 4c,d). In the absence of O2, the aldehyde
was not oxidized to the carboxylic acid, confirming that such a
conversion occurs through autoxidation.
Substrate Scope for Sequential One-Pot Oxidation.
Our MOF in-and-out method involved in controlling the
presence of MOF-TEMPO was tested for the sequential one-pot
oxidation of diverse substrates. Under our optimized conditions,
the conversion of alcohols to aldehydes (first step) was
monitored by TLC. When alcohols were completely trans-
As displayed in Scheme 4a, 3a was not produced when the first
step was not completed by the indication of the remaining 1a
(Scheme 4a). This result is consistent with the observation that
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formed to aldehydes, MOF-TEMPO was removed and the
second step was conducted. As illustrated in Scheme 5,
dioxane. As shown in Scheme 5, sequential oxidation reactions
of 2-furanmethanol (1q), 2-thiophenemethanol (1s), and 3-
thiophenemethanol (1t) were performed by forming the
corresponding carboxylate acids in good to excellent yields
(80−90%). Biomass-derived 5-(hydroxymethyl)furfural (1r,
HMF) was tested to be oxidized to 2,5-furandicarboxylic acid
(3r, FDCA), which has been the subject of many studies in both
homogeneous and heterogeneous catalysis. Notably, the
oxidation of 1r at para positions occurred, and 2,5-furandi-
carboxylic acid (3r) was generated in 88% yield.75 These overall
observations regarding the substrate scope highlight that our
MOF in-and-out method is useful for producing a variety of
carboxylic acids. Finally, the substrate scope was extended to
aliphatic alcohols by changing the solvent from CH3CN to ethyl
acetate. The conversion from alcohols to carboxylic acids was
observed in both CH3CN and ethyl acetate. Note that the
system using ethyl acetate achieved full conversion in a shorter
time, relative to that using CH3CN. 1-Hexanol (1u) and 1-
dodecanol (1w) were oxidized by our method affording the
desired hexanoic acid (3u) and dodecanoic acid (3w) (89 and
92%, respectively). In our previous study, the reactivity of the
TEMPO species onto the surface of MOFs was intensively
studied.34 Since the present MOF-TEMPO has active TEMPO
species on the surface, the substrate size discrimination with
large substrates was not attempted in this MOF in-and-out
method for the synthesis of carboxylic acids.
Scheme 5. Substrate Scope Tested for Producing Various
Carboxylic Acids via Our MOF in-and-out Method
Mechanistic Studies Employing 1H NMR and EPR
Spectroscopy. To identify the involvement of TBN in the
sequential oxidation reactions, we performed in situ NMR
studies in CD3CN, as depicted in Figure 1. We first found that
substituted benzyl alcohols with a wide range of functional
groups, heterocyclic alcohols, and aliphatic alcohols underwent
two-step oxidation to yield the desired carboxylic acids. Using
benzyl alcohols with distinct electronic (1a, 1b, 1e-1h, 1I, and
1p) and steric (1c, 1d, 1i, and 1j) properties, the corresponding
benzoic acids were obtained in very good to excellent yields
(83−99%). Unfortunately, functional moieties, including differ-
ent halogens (3k), amines (3m), and boronic esters (3n),
resulted in relatively moderate yields (50−65%).
It should be emphasized that the production of boronic ester-
substituted benzoic acid (3n) through sequential oxidation
reactions of 1n is very important. Compound 3n is not easily
generated via traditional oxidation reactions using strong
oxidants because the C−B bond is fragile.74 In addition,
terephthalic acid (3o), which is a representative ligand for
general MOFs and is industrially useful, was obtained in 81%
yield upon oxidation of 1,4-benzenedimethanol (1o) at para
positions. Given that the efficiency of the autoxidation of
heterocyclic aldehydes was not good under our optimized
conditions, these substrates were prepared under modified
conditions where the solvent was changed from CH3CN to 1,4-
Figure 1. In situ NMR studies of the second step. Experimental
conditions: [1a] = 0.25 M, [MOF-TEMPO] = 12.5 mM, [TBN] = 50
mM, and CD3CN.
TBN could form t-BuOH (after 0 h, ▽, Figure 1) in the first
step. Upon performing the second step, a new peak in the
aliphatic region was shown (▼, Figure 1). The intensity of the
new peak (▼) increased as the reaction progressed, and this
1
peak in the H NMR was not assigned to any known, tert-
butoxide-related compounds such as peroxides (Figure S4). As
expected, it was difficult to confirm the exact structure due to the
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unstable behavior of NOx,76 but in situ 1H NMR and GC−MS
analyses indicated the molecular species carrying the fragments
of tert-butyl and NxOx (Figures S4−S6). The peak (▼) was
observed only by elevating the reaction temperature, and the
second oxidation was initiated at 80 °C. Thus, both TBN and the
radical-terminating step could be activated by heating, and t-
next step. Finally, the aldehydes produced from the first step are
oxidized to their corresponding carboxylic acids through
autoxidation.73,87−91
Applications of the MOF in-and-out Method: Recy-
cling and the Antioxidative Effect. To confirm the
applicability of our method of oxidizing alcohols to carboxylic
acids of industrial and economic value in an environmentally
friendly manner, we designed gram-scale reaction conditions.
This testing can also verify the recovery and reusability of the
MOF catalyst employed in this work. As shown in Figure 2, the
1
BuONxOx may be monitored by H NMR. Regardless of the
change in the behavior of TBN, we detected 2a (◇) and 3a
(◆) when the reactions proceeded, and the peaks correspond-
ing to the expected byproducts such as peroxybenzoic acid were
not observed.
To determine the presence of active radical species at room
temperature as well as their elimination at 80 °C, additional
studies were conducted. The experiments with an NHC (N-
heterocyclic carbene) ligand, published by Lee and co-
workers,77 for trapping active radical species from TBN in the
second step were performed by employing EPR (electron
paramagnetic resonance) and NMR spectroscopy, as presented
in Figures S7 and S8. The 1H NMR studies confirmed that NHC
captured radicals and generated paramagnetic species when
TBN derivatives were exposed to O2 at 25 °C. When the TBN
derivative was exposed at 80 °C (the thermal treatment for the
1
second step), NHC showed inherent signals in both H NMR
and EPR. The EPR studies verified that TBN derivatives
maintained their radical character (expected for NHC-NO
species) when being exposed to O2 at room temperature, and
radical-free conditions from TBN derivatives could be obtained
at an elevated temperature of 80 °C. The observations of a
chemical shift in 1H NMR and distinct EPR signals by changing
the temperature, along with multiple control experiments
(Schemes 3 and 4), demonstrated that active radical species in
the reaction without MOF-TEMPO could be eliminated by
thermal activation. This alteration of the reaction environment
allowed the second step (the autoxidation of aldehydes to
carboxylic acids).
Figure 2. Recycling test of MOF-TEMPO for the sequential oxidation
of benzyl alcohol to benzoic acid.
recovered MOF-TEMPO was used for at least eight additional
cycles without the loss of its catalytic activity in the conversion of
1a to 2a. The autooxidation of 2a to 3a was successfully achieved
under an O2 atmosphere on the gram scale for each cycle. After
each run for aerobic oxidation (the first step), the MOF-
TEMPO solids were recovered by centrifugation, washed with
organic solvents such as CH3OH and CH3CN, and dried to
monitor their stability. The microscope and SEM (scanning
electron microscope) images of MOF-TEMPO (before the
reaction) after recovery showed no significant change in the
morphology (Figure S9). Then, the recovered MOF-TEMPO
solids were structurally analyzed by PXRD after several cycles, as
compared to the original MOF-TEMPO. The PXRD patterns of
the recovered MOF-TEMPO after one, three, four, five, and
eight cycles, as depicted in Figure S10, indicated that the main
peaks were retained, although the overall patterns were
broadened. This analysis suggested that the structural integrity
of MOF-TEMPO was relatively stable over several cycles. It
should be noted that similar PXRD patterns after recovery were
frequently observed with TEMPO-functionalized MOFs in the
literature.31,36,92 After the eighth run, the conversion of the first
step (aerobic oxidation) was slightly decreased (i.e., no full
conversion of the alcohol to the aldehyde). Since the remaining
alcohol can prevent the second step (autoxidation; Scheme 3),
the recycling test was not carried out further.
Scheme 6. Proposed Mechanisms for Sequential Oxidation
Reactions by Controlling the Presence of MOF-TEMPO
On the basis of the overall experimental results and previous
reports,78−86 Scheme 6 illustrates the proposed mechanisms for
the sequential one-pot oxidation reactions. Controlling the
presence of MOF-TEMPO is a critical factor in achieving such
oxidation reactions. TBN or TBN derivatives do not affect the
autoxidation in the second step after thermal treatment. As the
first step with MOF-TEMPO, the aerobic oxidation of alcohols
to aldehydes is in general thought to proceed via two previously
reported cooperative redox cycles: the oxidation cycle of an
external oxidant and the NO cycle associated with O2 and
water.69 After MOF-TEMPO is removed, the remaining TBN
naturally decomposes or becomes inactive adducts at 80 °C
(Scheme S1),76 which provides radical-free conditions for the
As an opposite approach, the protective effect of MOF-
TEMPO against the autoxidation of aldehydes to the
corresponding carboxylic acids was evaluated. This application
would be useful for keeping aldehydes relatively pure under
ambient conditions. After the incubation of 2a at 25 °C for 7
days in a scintillation vial without a cap, a total 45% conversion
to 3a was determined by 1H NMR, as illustrated in Figure 3. In
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(monitored by TLC), the desired product was isolated by silica
gel column chromatography with ethyl acetate and n-hexane.
CONCLUSIONS
■
The development of multifunctional MOF-based catalysts,
especially for tandem or sequential organic transformations, is
the important topic in heterogeneous catalysis. The fine-
tunability of MOFs opens up many possibilities for tandem
organic reactions in a single MOF pore; however, the
combinations of organic transformations are limited to chemo-
selective reactions. Although various heterogeneous catalytic
reactions directed by MOFs have been extensively studied with
respect to the aerobic oxidation of alcohols to aldehydes,
sequential two-step oxidation reactions from alcohols to
carboxylic acids in an MOF platform remain very challenging.
The two representative oxidations of organic molecules, the
aerobic oxidation of alcohols to aldehydes, and the autoxidation
of aldehydes to carboxylic acids cannot occur sequentially due to
their distinct mechanistic cycles, and this discontinuity has been
considered to be the benzaldehyde oxidation paradox in
common organic chemistry laboratories.
To achieve such challenging sequential oxidation reactions
without the consumption of catalytic TEMPO species, we
developed the MOF in-and-out method on the basis of carefully
analyzing the mechanisms of both the TEMPO-catalyzed
aerobic oxidation of alcohols to aldehydes and the radical-
inhibited autoxidation of aldehydes to carboxylic acids. The two-
step oxidation of alcohols to carboxylic acids succeeded under
mild conditions simply by managing the presence or absence of a
heterogeneous MOF-TEMPO catalyst and radical species. Our
MOF in-and-out method demonstrates a broad substrate scope
and is easily utilized in industrially applicable gram-scale
reactions. Additionally, the catalyst MOF-TEMPO can be
recycled multiple times by maintaining its catalytic activity. It
should be noted that previous homogeneous one-pot Fe-
TEMPO and electrochemical methods for the oxidation of
alcohols to carboxylic acids are not recyclable.
Our MOF in-and-out method also overcomes the incompat-
ibility of MOF catalysts with carboxylic acids produced from the
reactions. As the two main concerns regarding the compatibility
of carboxylic acids with MOF catalysts, trapping carboxylic acids
into the MOF pores and the additional coordination of
carboxylic acids to the MOF nodes are much less relevant in
our MOF in-and-out system than in previously reported studies.
Furthermore, MOF-TEMPO used as a catalytic platform in this
work highlights its recoverability from the solution because of
the heterogeneous characteristics of MOFs. The recoverability
of MOFs with excellent tunability and stability has not been fully
revealed as a great advantage, compared to their reusability and
reactivities in catalytic applications. Moreover, on the basis of
mechanistic studies of MOF-TEMPO, this MOF catalyst is
confirmed to be an excellent antioxidative stabilizer against the
undesired oxidation of aldehydes in reagent containers of
general laboratories.
1
Figure 3. H NMR spectra and pictures obtained from testing the
oxidation of benzaldehyde (top) with and (bottom) without MOF-
TEMPO.
the optical observation, the massive colorless precipitates (3a)
were detected after the incubation of 2a without MOF-TEMPO.
In contrast, the addition of 2 wt % MOF-TEMPO into the vial
containing 2a exhibited more than 99% purity of the compound
under the same conditions. Moreover, the TEMPO ligand and
Zr(IV) from MOF-TEMPO were not dissociated after the
reactions, as confirmed by 1H NMR and ICP-OES, respectively
(Figure 3; inductively coupled plasma−atomic emission spec-
troscopy (ICP-OES)). Together, the applications of MOF-
TEMPO shown in this study include the sequential two-step
catalytic oxidation reactions and the stabilization of aldehydes
against autoxidation. Such utilization is useful and practical
because MOFs are perfectly heterogeneous and their structures
and excellent stability can be fine-tuned through the
functionalization of organic ligands.
EXPERIMENTAL SECTION
■
Preparation of MOF-TEMPO. TPDC-TEMPO (214 mg,
0.42 mmol), ZrCl4 (96 mg, 0.42 mmol), and benzoic acid
(BzOH, 760 mg, 6.2 mmol) were placed in a 250 mL round-
bottomed flask with a magnetic stirring bar (3 mm × 6 mm), and
the solid mixtures were fully dissolved in DMF (DMF = N,N-
dimethylformamide, 16 mL). The mixture was stirred (300
rpm) at 120 °C in a heating mantle for 48 h and then cooled to
room temperature. The pale-pink octahedral crystals were
isolated by filtration and washed five times with fresh DMF (5 ×
10 mL), washed five times with MeOH (5 × 10 mL), and
washed five times with CH3CN (5 × 10 mL). Then heating to 40
°C under vacuum for 12 h yielded the activated MOF-TEMPO.
General Procedure for the MOF-TEMPO in-and-out
Method. Alcohol reagent (0.25 mmol), MOF-TEMPO (8 mg,
0.0125 mmol), and CH3CN (1 mL) were added to a scintillation
vial. tert-Butyl nitrite (5 mg, 0.05 mmol) was added to the
solution mixture, and then the mixture was stirred at 25 °C for
2−24 h under an O2 balloon (1 atm). The reaction was
monitored by TLC (thin-layer chromatography). When the
conversion of alcohol to aldehyde was complete (by TLC
monitoring), subsequently MOF-TEMPO was recovered from
the reaction mixture by a syringe filter. Approximately 2 × 0.25
mL of solvent (mainly CH3CN, 1,2-dichloroethane, or 1,4-
dioxane by a substrate) was used to prevent yield loss. Then the
reaction mixture was stirred for the second step under an O2
balloon (1 atm) at 80 °C for 10−24 h. After completion
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c02809.
Additional figures, schemes, and characterization data for
the obtained compounds (PDF)
G
https://dx.doi.org/10.1021/acs.inorgchem.0c02809
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
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AUTHOR INFORMATION
Corresponding Authors
■
Min Kim − Department of Chemistry, Chungbuk National
University, Cheongju 28644, Korea; orcid.org/0000-0002-
1710-2682; Email: minkim@chungbuk.ac.kr
Mi Hee Lim − Department of Chemistry, Korea Advanced
Institute of Science and Technology (KAIST), Daejeon 34141,
Korea; orcid.org/0000-0003-3377-4996;
Email: miheelim@kaist.ac.kr
Authors
Seongwoo Kim − Department of Chemistry, Chungbuk
National University, Cheongju 28644, Korea; orcid.org/
0000-0002-8929-3932
Ha-Eun Lee − Department of Chemistry, Chungbuk National
University, Cheongju 28644, Korea
Jong-Min Suh − Department of Chemistry, Korea Advanced
Institute of Science and Technology (KAIST), Daejeon 34141,
Korea
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Frameworks as Multifunctional Solid Catalysts. Trends Chem. 2020, 2,
454−466.
Complete contact information is available at:
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Author Contributions
§S.K. and H.-E.L. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Basic Science Research
Program (2019R1A2C4070584) and the Science Research
Center (2016R1A5A1009405) through the National Research
Foundation of Korea (NRF) funded by the Ministry of Science
and ICT. S.K. was supported by the NRF Global Ph.D.
Fellowship Program (2018H1A2A1062013) funded by the
Ministry of Education. The EPR experiment was supported by
the Institute for Basic Science (IBS-R010-D1) in Korea. We
thank Prof. Eunsung Lee (POSTECH, Korea) and Prof. Jinho
Kim (Incheon National University, Korea) for mechanistic
discussions with EPR and radicals. We also thank Younghu Son
and Prof. Minyoung Yoon (Kyungpook National University,
Korea) for assistance with MOF characterization.
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