Efficient acetalization of benzaldehydes using UiO-66 and UiO-67: Substrates accessibility or Lewis acidity of zirconium

Article abstract of DOI:10.1016/j.apcata.2015.08.028

Porous metal-organic frameworks of Zr₆O₄(OH)₄ clusters connected by organic linkers of 1,4-benzenedicarboxylate (UiO-66) and biphenyl-4,4′-dicarboxylate (UiO-67) were prepared using a solvothermal method and used as efficient catalysts for acetalization of benzaldehydes with alcohols. UiO-66 showed better catalytic activity than UiO-67, (i.e. 91% vs 86%) when the catalyst was employed in the benzaldehyde acetalization in methanol for an hour at r.t. (28 °C). UiO-66 was further explored as the catalyst to observe effects of catalyst concentrations, alcohols, bulkier benzaldehydes, and recyclability. The performance of other catalysts, including the MOF precursor, was also examined to compare the activity and to explain the importance of a MOF structure. Relative Lewis acidity of Zr in UiO-66 and UiO-67 was achieved by natural bond orbital (NBO) analysis using DFT/B3LYP method. It was found that accessibility of substrates to internal active sites might play a dominant role than the Lewis acidity of Zr-MOFs.

Full text of DOI:10.1016/j.apcata.2015.08.028

Accepted Manuscript
Title: Efficient Acetalization of Benzaldehydes using UiO-66
and UiO-67: Substrates Accessibility or Lewis Acidity of
Zirconium
Author: Ubed S.F. Arrozi Husni W. Wijaya Aep Patah Yessi
Permana
PII:
S0926-860X(15)30123-X
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2015.08.028
APCATA 15522
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Applied Catalysis A: General
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Revised date:
Accepted date:
12-6-2015
19-8-2015
22-8-2015
Please cite this article as: Ubed S.F.Arrozi, Husni W.Wijaya, Aep Patah, Yessi
Permana, Efficient Acetalization of Benzaldehydes using UiO-66 and UiO-67:
Substrates Accessibility or Lewis Acidity of Zirconium, Applied Catalysis A, General
http://dx.doi.org/10.1016/j.apcata.2015.08.028
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Efficient Acetalization of Benzaldehydes using UiO-66 & UiO-67:
SubstratesAccessibilityor Lewis Acidity of Zirconium
Ubed S. F. Arrozi, Husni W. Wijaya, Aep Patah*, Yessi Permana*.
Inorganic & Physical Chemistry Research Division, Institut Teknologi Bandung,
Jl. Ganesha 10, Bandung, 40132, Indonesia
* Corresponding authors: aep@chem.itb.ac.id (AP) and yessi@chem.itb.ac.id (YP)
Graphical abstract
fx1
Highlights

UiO-66 and UiO-67 were studied in acetalization of benzaldehydes with alcohols.
Effect of nature of linker ligands on Lewis acidity and catalytic properties was studied.
Relative Lewis acidity of Zr in UiO-67 is higher than that in UiO-66.



Reaction rate of acetalizations catalyzed by UiO-66 is faster than that by UiO-67.
Abstract: Porous metal-organic frameworks of Zr6O4(OH)4(CO2)12 clusters connected by organic linkers of
1,4-benzenedicarboxylate (UiO-66) and biphenyl-4,4′-dicarboxylate (UiO-67) were prepared using a
solvothermal method and used as efficient catalysts for acetalization of benzaldehydes with alcohols. UiO-66
showed better catalytic activity than UiO-67, (i.e. 91% vs 86%)when the catalyst was employed in the
benzaldehyde acetalization in methanol for an hour at r.t. (28 C). UiO-66 was further explored as the catalyst
to observe effects of catalyst concentrations, alcohols, bulkierbenzaldehydes, and recyclability. The
performance of other catalysts, including the MOF precursor, was also examined to compare the activity and
to explain the importance of a MOF structure.RelativeLewis acidity of Zr in UiO-66 and UiO-67 was
achieved by natural bond orbital (NBO) analysis using DFT/B3LYP method. It was found that accessibility of
substrates to internal active sites might play a dominant role than the Lewis acidity ofZr-MOFs.
Keywords: UiO-66, UiO-67, acetalization, catalytic properties, Lewis acidity, NBO analysis.

1. Introduction
Acetalization is one of widely used synthetic strategies for protecting carbonyl group of ketones and
aldehydes [1,2]. Acetalsareimportant reactants for synthesizing functional compounds including steroids,
pharmaceuticals, and fragrances[3]. Such a reactionwasgenerally carried out by reacting a carbonyl compound
with an alcohol (Scheme 1) and/or corresponding trimethyl orthoformate[4]. Reported catalysts employed in
such reactions include CoCl2[4], LaCl3[5], NCS/thiourea[6], 1,4-dimethyl-1H-1,2,4-triazol-4-ium iodide[7],
ruthenium(III)-polyvinyl pyridine complex[8], indium(III) fluoride[9], 3-methyl-1-
(methoxycarbonylmethyl)imidazolium tetrafluoro-borate[10], hydroxylamine hydrochloride; lithium
carbonate[11], and ruthenium trichloride/trimethyl orthoformate adduct[12]. However, numerous attempts to
improve the atom efficiency have become a great demand. This includes elimination of dehydrating agents
and the use of recyclable catalysts. The utilization of heterogeneous catalysts offers easy catalyst recovery and
recycling, as well as product separations[13]. Indeed, several heterogeneous catalysts have been reported in
acetalization reactions, such as mesoporous aluminosilicates[14], MCM-41, JRC-SiO-4, and silica
gel[15].However, factors affecting their catalytic activities, such as Lewis acidity and substrateaccessibility
into active sites,need to be elaborated.
Metal-organic frameworks (MOFs) have received much attention in recent years due to their wide potential
applications such as gas storages, gas separations, sensors, luminescence, drug deliveries, and catalyses[16-
20]. Their unique properties contribute widely to their applications, i.e. high surface area, tunable pore size,
ease of processability, structural diversity, and geometrical control[21]. In the field of catalyses, MOFs are
able to serve as catalysts or as catalyst-supports for several organic transformations[22], such as Friedel-Crafts
acylations[23], Pall-Knorr reactions[24], Knoevenagel reactions[25], cyanosilylation[26,27], ring-opening of
epoxides[28], aerobic oxidations[29], hydrogenations[30], Suzuki-Miyaura cross-coupling[31], and
transesterifications[32]. Among more than 20,000 known MOFs, there are several transition metal-based
MOFs that have shown stability under liquid-phase reaction conditions[33,34], including porous zirconium-
based MOFs which consist of zirconium clusters (Zr6O4(OH)4) as building units [35] and organic linkers of
1,4-benzenedicarboxylate (UiO-66, UiO = University of Oslo) or biphenyl-4,4′-dicarboxylate (UiO-67). Both
materials were reported to demonstrate good stability at high temperature (up to 540 C) and high mechanical
pressure (up to 10,000 kg/cm2)[35a]. These MOFs are also stable in water and common organic solvents[35a].

UiO-66 was reported to have high activity in various organic reactions, such as epoxidation of
cyclooctene[36], CO2 cycloaddition of styrene oxide[37], and cyclization of citronellal[38]. Timofeeva et
al.[39] has also reported the effect of –NH2or –NO2 group functionalized 1,4-benzenedicarboxylate linker in
the UiO-66 structure and observed its catalytic activity on acetalization of benzaldehyde with methanol. The
results showed that functionalization of an organic linker with an electron withdrawing group (O2N-H2BDC)
increased the catalytic activity, while employment of –NH2 moiety as an electron donating group gave lower
catalytic activity. Employment of MOFs with identical organic linkers yet different metal centers, namely
Cu3(BTC)2 (BTC =1,3,5-benzenetricarboxylate), Fe(BTC), and Al2(BDC)3 (BDC = 1,4-
benzenedicarboxylate),in the same benzaldehyde acetalization showed different catalytic activity, i.e.,catalytic
activity of Cu-based MOF washigher than FeandAlones, with benzaldehyde conversion of 88%, 71% and
66%, respectively[40]. Differences affected by metals and organic linkers suggested the need of a thorough
investigation in this field.
In this work, we report the exploration of UiO-66 and UiO-67 on acetalization of benzaldehydes with
alcohols, includingthe effect of a Zr-MOF structure compared to its precursors (organic linker and ZrCl4),the
effect of pore sizes, andthe effect ofrelative Lewis acidity of Zrat UiO-66 and UiO-67. Relative Lewis acidity
were achieved using a natural bond orbital (NBO) analysis, calculated by Density Functional Theory (DFT)
method. The effect of substrates accessibility was studied from catalytic results and pore sizes of the MOFs.
2. Experimental
2.1 Material and Instrumentation
1,4-Benzenedicarboxylic acid(H2BDC), biphenyl-4,4′-dicarboxylic acid(H2BPDC) and 3,5-di-tert-butyl-2-
hydroxybenzaldehyde were purchased from Sigma-Aldrich. N,N-dimethylformamide (DMF), zirconium(IV)
chloride, benzaldehyde, 2-hydroxybenzaldehyde, methanol, ethanol, CoCl2, naphthalene, and chloroform
were commercially obtained from Merck. All reagents and starting materials were used as received without
any further purification.
X-ray powder diffraction (XRD) patterns were recorded using CuKα radiation source on a Bruker D8
Advance XRD. Nitrogen physisorption measurements were conducted bya Quantachrome Autosorb iQ-AG
system with samples pretreated by heating under vacuum at 200 C for 6 hours and measurement temperature

of 196C. Thermogravimetric measurements were conducted by a thermal analyzer NetzschSTA 449 F1
Jupiter with heating rate of 40 K/min in argon atmosphere. A Bruker Alpha instrumentwas used to collect
Fourier transform infrared (FTIR) spectra with samples being dispersed on potassium bromide pellets. The
spectrum was generated in resolution of 2 cm1, collected 16 times, and corrected for a background noise.
Scanning electron microscope (SEM) analysis was carried out by JEOL-JSM-6510LV. Gas chromatography
(GC) analyses were performed using a Techcomp GC-7900 with a flame ionization detector (FID) and a
Kromat KB-1 (100% polydimethylsiloxane)capillary column (length = 15m, inner diameter = 0.25mm, and
film thickness = 0.25µm). Temperature program for GC analyses was set at 100C for 1 min and raised to 190
C at rate of 30 C/min and from 190 C to 210 C at rate of 10 C/min. The temperature was finally kept for
5 min at 210 C. Naphthalene (0.078 mmol) was used as an internal standard to calculate reaction
conversions. 1HNMR spectra were recorded on a JEOL JNM ECA 500 spectrometer.
2.2 Synthesis of UiO-66 and UiO-67
UiO-66 was synthesized by a solvothermal method according toreported procedures[35] with some changes in
molar ratio of ZrCl4: H2BDC: DMF. In our typical preparation, ZrCl4 (0.208 g, 0.893 mmol) was dissolved in
20 ml of DMF, then the mixture was added by 0.148 g of H2BDC(0.893 mmol) under nitrogen atmosphere at
r.t. (28 C). The obtained mixture was sealed in a solvothermal autoclave and placed in a pre-heated oven at
120 C for 24 hours. Crystallization was allowed in a static condition. After cooling to r.t., the mixture was
filtered and washed three times with 5 ml of DMF at r.t. and filtered to give white solid precipitates. The
precipitates wereimmersed in 10 mL of chloroform at r.t.and replaced daily for 3 times. The materials
weredried in vacuo at 140 C for 8 hours, yielding white powder crystals. UiO-67 was synthesized with the
same procedure as above by replacing H2BDC to H2BPDC as the organic linker. Formations of UiO-66 and
UiO-67 were confirmed from their XRD patterns (supplementary material; Fig. S2) as reported in the
literature [35, 41].
2.3 Catalytic studies
Prepared Zr-MOF catalysts were activated prior to catalytic test by drying the catalyst in vacuo at 140 C for 8
hours. A 50 ml Schlenk tube was charged with 50 mg of the catalyst, 3 mL of methanol(74 mmol), 0.98
mmol of substrate (benzaldehydes), and 0.078 mmol of naphthalene as an internal standard. The reaction

mixture was then stirred at 500 rpm atr.t.(28 C) and for a required time. Reaction conversions were
monitored by taking aliquots from the reaction mixture at different time intervals and analyzed by GC with
naphthalene as an internal standard.The product was also confirmed by 1H NMR (analyses of the product by
GC and 1H NMR are available in the supplementary material; Fig. S8 and S9). The catalyst wasseparated by
centrifugation and dried in vacuo at 140 C for 3 hours and reemployedfor recyclability tests.
2.4 Computational Details
The calculation of geometry optimizations and NBO analyses were performed on High Performance
Computing (HPC) system of Institut Teknologi Bandung (ITB). All calculations in this work were performed
using Gaussian 09 software package. Becke three-parameter hybrid method combined with the LYP
correlation function (B3LYP) was used for the DFT calculations [42]. The LANL2DZ basis set was used for
Zr atom [43], while 6-31G(d) basis set was used for C, H, and O atoms. The NBO (natural bond orbital) 3.1
program included in the Gaussian 09 package was used to analyze the Lewis acidity of Zr-MOFs.
3. Results and discussion
3.1 Preparation of UiO-66 and UiO-67
UiO-66 and UiO-67 were initially reported by the Lillerud group from University of Osloto havea cubic close
packed (CCP) structure, of which the cluster wasa 12-coordinated complex, resulting in nanosized pore-
materials [35]. The utilization of MOFs in many applications, particularly as catalysts such as the one in our
work, requires evacuation of guest molecules especially trapped-solventsderived from the synthesis process.
This activation becomes an important point not only to avoid pore blockage [44], but also to expose more
active sites in the frameworks. For that reasons, solvent-exchange inas-synthesized UiO-66 and UiO-67 was
carried out by replacing DMF (bp = 152 C) with excessive chloroform (bp = 61 C). Immersing the Zr-MOFs
in chloroform and heating them under reduced pressure allowed the removal of DMF[13].
The obtained powder was characterized by FTIR, XRD, TGA, SEM, and N2 physisorption (provided in the
supplementary material). The high crystalline phase of synthesized Zr-MOFs were confirmed by powder
XRD analysis to be UiO-66 and UiO-67 as indicated from characteristic diffractions at2θ of 7.4 and 8.5
degrees for UiO-66 and 5.7 and 6.5 degrees for UiO-67 (supplementary material; Fig. S2). Lower angle-shifts
of d111 and d200 reflections in UiO-67compared to ones in UiO-66were indicated the employment of longer

linker of BPDC between the building unit of Zr6O4(OH)4in UiO-67. These results were ingood agreement
with previously reported UiO-66 & 67 by the group of Lillerud [35,45].FTIR spectra showed that the carbonyl
vibration at free ligands has shifted to weaker wavenumbers at Zr-MOFs and vibrations of hydroxyl moety at
free ligand were no longer presence at Zr-MOFs (supplementary material; Fig. S1). The spectra also showed
the presence of Zr-O vibrations[35b]in UiO-66 (668 cm1) and UiO-67 (663 cm1).
Thermal gravimetric analysis (TGA) profiles of these MOFs also showeda thermal resistance up to 600C
which was in good agreement with reportedliteratures[35,45]. The SEM images of UiO-66 & 67 showed that
those materials were in the form of agglomerates as seen in the previously reported morphology [35,45,46].
Surface area measurement is a significant parameter in MOFs. Therefore, the MOFs were tested by N2
physisorption. The BET (Brunauer-Emmett-Teller) surface areas of synthesized UiO-66 and UiO-67 were 901
and 490 m²/g, respectively, while pore size (BJH method)of these MOFs were 3.17 nm (UiO-66) and 3.01 nm
(UiO-67). Here, the synthesized UiO-66 was higher in surface area and pore size than the reported literature
by Ebrahim et al[46], while the synthesized UiO-67 showed a reverse result [45, 46]. Heating the as-
synthesized UiO-67 at 170 C in vacuo for 6 days resulted in surface area of 140 m2/g. Prolonged activation
of synthesized UiO-67 for additional 4 days only increased the surface area to 490 m2/g. Thus, no further
attempt was conducted to increase the surface area of the synthesized UiO-67 by such a method. The lower
surface area and pore size of synthesized UiO-67 was likely caused by trapped-DMF molecules inside the
UiO-67 structure or coordination of the solvent to Zr vacant sites. We then employed these MOFs as catalysts
in acetalization reactions of several aldehydes and alcohols with various parameters affecting the catalytic
activity.
3.2 Catalytic activities of UiO-66 and UiO-67
Initial study was conducted by comparing catalytic activities of UiO-67 and its precursors (a mixture of ZrCl4
and H2BPDC)(Fig. 1). This study addressed the importance of MOF structure as a catalyst in acetalization
reactions. Benzaldehyde and methanol were used as a model reaction. Reaction conditions (r.t. of 28 C, 0.98
mmol benzaldehyde, 74 mmol methanol)and concentrations of MOF precursors were set to be the same
asconcentration of UiO-67 catalyst (a mixture of 0.09 mmol ZrCl4 and 1.7 mol eq. of H2BPDC,that was
equivalent to the preparation of 50 mg UiO-67). Figure 1 shows that in the absence of a catalyst, the reaction

at 28 C for 1 hour gave 19% benzaldehyde conversion (Fig 1, f). Such a reaction was probably catalyzed by a
proton in the reaction mixture. The acidity of the mixture (pH = 5) confirmed this phenomenon.
Catalytic tests were further investigated using ZrCl4 as zirconium precursor for Zr-MOFs. Methanolysis of
benzaldehyde by 30 mg of ZrCl4(0.13 mmol) in fact gave higher conversion than the reaction without catalyst
(Fig. 1; c vs f). The conversion was even higher with the increase of ZrCl4 concentration (Fig. 1; b vs c).
However, an increase of ZrCl4 concentration up to 70 mg (0.30 mmol; 30.6 mol% based on benzaldehyde)
was still lower than the employment of 50 mg of UiO-67, which was prepared from ZrCl4 of 0.09 mmol(Fig.
1; b vs a). To observe a contributed effect of free ligand, the reaction was also tested using H2BPDC as a
catalyst. The result showed that in an hour, 12mol%H2BPDC was able to convert 43% of benzaldehyde into
benzaldehydedimethylacetal. This can be rationalized by the presence of Bronsted protons at H2BPDC. In
fact, the pH of this free ligand in wet methanol was 4.
Employment of UiO-67 precursors, i.e. a mixture of ZrCl4 and H2BPDC, in equivalent amounts of those
required to generate 50 mg of UiO-67, was also performed (Fig. 1, e). Such a mixture gave benzaldehyde
conversion of only 35%, lower than that of UiO-67 (85%; Fig. 1; e vs a). Thus, the highest conversion was
achieved when the structure of a catalyst was as a framework of UiO-67 rather than as its precursor. Such a
fact was possibly attributed by electron withdrawing character of H2BPDC linker which therefore reduced
electron density at Zr cluster in comparison to ZrCl4. The electron density reduction at Zr is ascribed to the
increase of Lewis acidity of UiO-67 as a whole. Possible active sites at UiO-67 are exchangeable
coordination positions around the Zr ion clusters [47] and unsaturated site at Zr ion clusters. In fact, in the
structure of UiO-66, not all of Zr ions were reported to be fully coordinated[35b]. This results in unsaturated
sites of Zr ions which act as vacant sites.
The kinetic and reaction mechanism of acetalization catalyzed by heterogeneous catalysts with Lewis
acidicactive sites have been studied, for examples, with the employment of zeolites and MIL-101/PTA
[48,49]. In this work, we attempted to observekinetic profile of the catalyst during the reaction by taking
aliquots from the mother liquor at different time intervals and analyzed them by GC. Conversion profiles and
kinetic profiles of UiO-66 and UiO-67 in benzaldehydes acetalization with alcoholsare provided in Fig. 2 and
3.

Slow induction period of UiO-67 (16% conversion within 15 min) in comparison to UiO-66 (86% conversion
within 15 min) showed a diffusion limitation of substrates into active sites likely because of pore blockages in
UiO-67. Prolonged reaction up to 24 hours gave lower benzaldehyde conversion than that of an hour reaction
(Fig. 2), indicating a reverse hydrolysis of the acetal product. To avoid such a reverse reaction, we monitored
reactions within an hour.In contrast to the finding by Timofeeva and co-workersthatreported a much lower
UiO-66 activity on benzaldehyde acetalization within 1 hour (conversion of ca. 13%) [39], we observed that
UiO-66 was very active in the same reactioncondition (conversion of 91% within an hour). This was
probablybecause ofthe presence of nitrobenzene as an internal standard in the Timofeeva’s reaction. Initial
experiments employing naphthalene in the absence of catalysts showed no effect of naphthalene as an internal
standard to our reactions (supplementary material; Table S2).
The presence of Lewis acidic sites was confirmed by addition of pyridine in equimolar amount to
benzaldehyde in the reaction mixture. As pyridine may strongly coordinate to Lewis acidic metals, thus the
active site is likely to be at Zr atoms when Lewis acidity attributed by Zr was poisoned[40,52]. Here,
poisoning of UiO-66 by pyridine indeed decreased the activity of the MOF drastically to 21% for an hour
reaction (Fig. 2-c).
Figure 3 describes the reaction to be second order to benzaldehyde, and thus it gives straight lines in the plot
of 1/[benzaldehyde] (M1) vs t (minutes). On the other hand, assuming the reaction was first order to
benzaldehyde and approaching it as a pseudo-first order rate, we obtained non-linear lines from the graphic of
[ꢀꢁꢂꢃꢄꢅꢆꢁꢇꢈꢆꢁ]
ln
ꢉvs t (minutes) (supplementary material, Fig. S6).
[ꢀꢁꢂꢃꢄꢅꢆꢁꢇꢈꢆꢁ]
ꢊ
Rate constants (kobs)thus can be calculated by a slope resulted from each line in Fig. 3, i.e., 1.05 M1·min1 for
reaction catalyzed by UiO-66 and 0.05 M1·min1 for UiO-67. These rate constants can be used further to
determine turnover number (TON) by using expression of TON = [ꢀꢁꢂꢃꢄꢅꢆꢁꢇꢈꢆꢁ] . %ꢌꢍꢂꢎꢁꢏꢐꢑꢍꢂmeasured at 1
ꢋ
[ꢌꢄꢒꢄꢅꢈꢐꢒ]
hour.[49] Approximating Zr content in UiO-66 and UiO-67 are equally 30% [50], TON of benzaldehyde
acetalization with methanol catalyzed by UiO-66 and UiO-67 are 556 and 523, respectively.

This result indicates that although Zr at UiO-67 has a relativelybetter Lewis acidity, UiO-66 showed better
catalytic activity in the first hour of reaction. This is probably caused by a poor accessibility of substrates into
active sites of UiO-67 than into UiO-66.It is noteworthy to mention that although the BET surface area of
UiO-67 (491 m2/g) was measured to be lower than that of UiO-66 (901 m2/g), the high crystalline of the two
MOFs and lower-angle shifts of characteristicd111 and d200 reflections in UiO-67 XRD patterns(which
described the lengthening of d spacing, supplementary material; Fig. S2)explained that the drop in surface
area was suggested due to a pore blockage likely by trapped- or coordinated-DMF solvent instead of a
significant drop in number of Zr clusters per identical mass. This, therefore, suggested that the employment of
the same mass of 50 mg Zr-MOFs in the catalytic test by which the surface area of UiO-67 is about half of
UiO-66 does not directly describe a drop ofZr content in UiO-67.
3.3 Relative Lewis acidity of Zr and substrate accessibilityin UiO-66 and UiO-67
A comparison of two MOFs with the same metal, yet with different length of linkers has also been studied by
Nguyen L. T. L., et al.[23] They compared Zn-based MOFs containing 1,4-benzenedicarboxylate (MOF-5)
with 2,6-naphthalenedicarboxylate organic linker (IRMOF-8) for a Friedel-Crafts acylation of toluene, of
which the surface area of MOF-5 was reported to be higher than that of IRMOF-8, while the pore size of
MOF-5 was in reverse [23]. The result showed that IRMOF-8 gave higher conversion than MOF-5 in the
same reaction condition. This described that accessibility of substrate to active sites was more pronounced
than surface areas. However, limited knowledge is available on the effect of those different ligands with
Lewis acidity.
Herein we attempted to distinguish the Lewis acidity of Zr in UiO-66 and UiO-67by means of a
computational approach. TheseMOFshave the same metal anda similar structure. They only differ in linkers.
Computational study to examine Lewis aciditiesof MOFs containing copper and 2 different linkers (5-
methylisophtalate and 1,3,5-benzenetricarboxylate)were reported by the group of Zhong [42]. The structure
of perfect Zr-MOFs contain 12-coordinated ligands for each clusters of Zr6O4(OH)4.[35b] In fact, the group of
Lillerud observed that as-synthesized UiO-66 showed a weaker thermal strength compared to a modeled UiO-
66 of perfect 12-coordinated MOF, which indicated a defect structure of UiO-66 [35b]. Therein they proposed
11 ligands were coordinated in the zirconium framework. Here we calculated the Lewis acidity of UiO-66 and
UiO-67with structures of 11-coordinated ligands in each cluster and lefta vacant site at Zr atom. Geometry

optimizations of these Zr-MOFs were performed by considering cationic structure of +1 charge and
multiplicity of singlet for all models. After acquiring optimized geometry of these models using B3LYP
methodwith basis sets of LANL2DZ for Zr and 6-31G(d) for C, H, and O atoms(Fig. 4), analysis of Lewis
acidity of such MOFs were further performed using natural bond orbital (NBO) analysis. Different ligands
mayprovide different electron density at each metal centers. Higher electron withdrawing character of a ligand
may lowerelectron density atZr, and thus increase Lewis acidity of aZr-MOF. We found that thenatural charge
of Zr in11-coordinated UiO-66 was higher than that in UiO-67 (Table 1). Thus, relative Lewis acidity of Zr in
UiO-67 is higher than that inUiO-66, by which theoretical activities of such Zr-MOFs were inreverse to
experiments. As UiO-66 experimentally gavehigher catalytic activity and pore size distribution than UiO-67,
the reverse result between experimental activitiesandcalculated Lewis acidityindicated a dominant factor of
substrate accessibilitiesintoactive sitesoverthe Lewis acidity of the catalyst.
As catalyst concentration plays an important role towardshigh yield of products, we also studied the effect of
UiO-66 quantity in the benzaldehyde acetalization. Employment of 5, 10, and 50 mg of UiO-66 to the reaction
showed that the smallest concentration gave the lowest conversion (Fig.5c). Increasing the quantity of the
catalyst indeed enhanced the conversion (Fig. 5b). However, a further increase of the catalyst did not further
increase significantly the catalytic conversion(Fig. 5; b vs a). Thus, herein we employed UiO-66 of 10 mg to
further investigate other parameters affecting catalytic reaction.
We were also interested in investigating the effect of ethanol as anothertype of alcohol in this reaction.
Ethanol was used in equimolarin the reaction, carried out with UiO-66. Significant decrease of conversion
was observed when ethanol was used as an alcohol source (13%),in comparison to that of methanol (93%)
(Fig. 6, a vs d). Such results indicated that the longer alkyl carbon of ethanol likely reduced its diffusion into
internal surface of UiO-66 at which the reaction likely took place predominantly, and hence the reaction rate
and benzaldehyde conversion decreased significantly [13,40]. The fact also implies that the entrance of
substrates to active sites plays a dominant role in determining the overall rate.
Anhydrous cobalt chloride has been reported to be active in benzaldehyde acetalization [4]. To provide a
comprehensive understandingof a reaction site at UiO-66, we then conductedanalog reactions with anhydrous
CoCl2 either for benzaldehyde methanolysis or benzaldehyde ethanolysis (Fig. 6b and c).The catalytic activity
of UiO-66 clearly showed a great superiority than CoCl2 for benzaldehyde methanolysis(Fig. 6a vs b).

However, a homogeneous phase of CoCl2gave better conversion than UiO-66 when longer chain of ethanol
was selected as the substrate(Fig. 6c and d; conversion of 37% and 25%, respectively). As the size of
catalystpores and the size of substrates gave a significant influence to the reactivity, this result implies that the
reaction catalyzed by UiO-66 was taken place at internal surfaces.
We also assessed how the size of benzaldehydesaffectedto the reactivity. Herein, we examined
otherbenzaldehyde derivatives, i.e. 2-hydroxybenzaldehydeand 3,5-di-tert-butyl-2-hydroxybenzaldehyde.
Reactions were carried out using 10 mg of UiO-66 in methanol for an hour. As shown in Fig. 7, the smallest
benzaldehyde gave the highest conversion(Fig. 7-a), while 2-hydroxybenzaldehyde resulted in lower
conversion (53%; Fig. 7-b). In addition, larger size of 3,5-di-tert-butyl-2-hydroxybenzaldehyde only
gave1%of conversion(Fig. 7-e).This explains that bulkier substrates hardly diffuse to internal active sites of
UiO-66. To further support our conclusion, we examined the same reaction usingCoCl2, a complex that has
been reported to be active in acetalization of benzaldehydes[4]. Graphic b and c in Fig. 7gave comparison of
2-hydroxybenzaldehyde acetalization with methanol using UiO-66 and CoCl2. Here we still observed a
superiority of UiO-66 in comparison to homogeneous phase of CoCl2. However, acetalization of a larger
benzaldehyde of 3,5-di-tert-butyl-2-hydroxybenzaldehydeusing UiO-66 gave lower catalytic activity than
CoCl2(Fig. 7e). This supports our previous conclusion that the reaction site was at internal surface of UiO-66
and not at external surface.
To consider UiO-66 as an efficient catalyst, we compared it to other homogenous and heterogeneous catalysts.
The experiments were adjusted to have similar reaction conditions with UiO-66 (Table 2). At
first,conventional Lewis acid such as ZnCl2 and CoCl2 in the same phase with the reaction mixture were
employed for this acetalization of benzaldehyde and methanol. These catalysts gave lower activities than UiO-
66 with conversion of 40% and 34%, respectively. A reaction catalyzed by ZnCl2 for 24 hours gave lower
conversion (39%). Compared to other reported MOFs as heterogeneous catalysts, UiO-66 also shows higher
catalytic efficacy than Cu3(BTC)2, Fe(BTC), Al2(BDC)3,[38] InF3,[9] and mesoporous aluminosilicate[14] in
1 hour of reactions. To further enhance the catalytic activity of UiO-66, functionalization of the organic linker
with electron withdrawing group, [39,52] and the addition of dehydrating agent such as trialkyl
orthoformate[53] become alternative routes to be studied.

In the field of heterogeneous catalyst, a metal leaching during the reaction is considered as an
important issue. In this respect, Timofeeva and co-workers[39] has confirmed the absence of a leaching
process in UiO-66,by which a catalytic reaction using UiO-66 resulted no change ofconversion when the
catalyst was separated from the solution and the reaction was continued to longer reaction time.
3.4 Recyclability of UiO-66 and UiO-67
One of the advantageous of heterogeneous catalyst is the ease of separation and its recyclability. A test of
recyclability of UiO-66 in the acetalization of benzaldehyde and methanol was performed up to 4 runs. After
the initial run, UiO-66 was separated bycentrifugation and dried under vacuum in 140 C for 6 hours. The
recycled UiO-66 was then reused in the same reaction and monitored by GC for an hour. Here UiO-66 was
observed to demonstrate no significant loss in activitywhen it was recycled up to 4 runs(Fig 8), which was
identical with a work by Timofeeva[39].
To observe a possibility of structural deformation and its effect on catalytic activity, the recycled UiO-66was
characterized by FT-IR and PXRD. FT-IR analysisshowed no change of characteristic vibrationsbefore and
after being employedin the reaction(Fig. 9). However broaden peaks around 5001000 cm1and 15001750
cm1 indicated the presence of remained organic compounds from the reaction which might blockage the pore
and explained a slight reduction in activity of the following runs. The PXRD analysisalso demonstrated a drop
of structural crystallinity in the second run ofUiO-66 (41%) compared to the fresh one (71%)(Fig. 10). This
significant structural deformation however gave no dramatic effect to its catalytic activity, of which the
second run catalyst still achieved 91% conversion in the reaction. This phenomenon thus reflects no
significant influence of substrate diffusion into deformed catalyst.
4. Conclusions
UiO-66 and UiO-67 were preparedusing a solvothemal method with a slight modificationon molar ratio of
ZrCl4:H2BDC/H2BPDC:DMF. The MOFs were characterized by FT-IR, PXRD, TGA, and N2 physisorption
and employed in acetalization reactions of benzaldehydes with alcohols. Active sites of the MOF were

identified bya pyridine test, by which pyridine likely poisoned the exisiting Lewis acidic site of
zirconium.UiO-67 gavehigher catalytic activity compared to its precursors (ZrCl4 and H2BPDC), showing the
importance of MOF structure formation in catalysis. Yet,UiO-67has a lower catalytic activity compared to
UiO-66. An NBO analysis using DFT/B3LYP method gave information on relative Lewis acidities of Zr in
UiO-66 and UiO-67. The relative Lewis acidity order was observed to be UiO-67 > UiO-66. Although Zr in
UiO-67 was observed to have higher Lewis acidity than that in UiO-66, we observed that accessibility of
substrates into active sites was likely more dominant than the Lewis acidity in this catalytic reaction. Further
studies using UiO-66 as the catalyst showed that the reaction took place predominantly inside the pore, and
therefore bulkier substrates was catalyzed slower. Recyclability studies of UiO-66 also shows that UiO-66
may act as a Lewis acid catalyst up to 4 runswith no significant loss in activity.
Acknowledgement
USFAthanks to BU-DIKTIscholarship for Master Program at Chemistry Department of ITB.AP and YP
acknowledge Hibah IA-ITB 2011 and Hibah Desentralisasi Dikti 2015 for financial support on Zr-MOFs
research and also for Hibah Kerma-LN DIKTI 2012 for partial support on catalysis research using
organic/inorganic hybrid materials. Authors acknowledge HPC (High Performance Computing) facilities at
ITB and thank to Dr. Muhamad Abdulkadir Martoprawiro,Dr. Muhammad Yusuf, Mr. Raden Aditya
Wibawafor fruitful discussion on DFT-NBO calculations.

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Scheme 1. Acetalization of benzaldehyde in methanol solvent.
Figure 1. Conversion profiles for benzaldehyde acetalization in an hour, catalyzed by (a) 50 mg UiO-67; (b)
70 mg ZrCl4 (0.30 mmol); (c) 30 mg ZrCl4(0.13 mmol); (d) 30 mg H2BPDC (0.12 mmol); (e) a mixture of
ZrCl4 (21 mg, 0.09 mmol) and H2BPDC (28 mg,0.16 mmol) (equivalent to the preparation of 50 mg UiO-67);
and (f) blank (no catalyst). Reaction condition: benzaldehyde (0.98 mmol), methanol 3 mL (74 mmol), r.t. of
28 C.
Figure 2. Conversion profiles of benzaldehyde acetalization within an hour,catalyzed by (a) UiO-66; (b) UiO-
67; and (c) pyridine/UiO-66. Conversion by UiO-66 and UiO-67 after 24 hours were also taken (a and
b).Reaction condition: benzaldehyde (0.98 mmol), methanol 3 mL (74 mmol), r.t. of 28 C.
Figure 3. Initial reaction rate of benzaldehyde acetalization with methanol catalyzed by(a) UiO-66 and (b)
UiO-67.
Figure4. (a) Modeled structures of (a) UiO-66 and (b) UiO-67 optimized by DFT/B3LYP method.
Figure5. Effect of catalyst concentrationonacetalization of benzaldehyde, catalyzed by UiO-66, (a) 50 mg, (b)
10 mg, and (c) 5 mg. Reaction condition: r.t., benzaldehyde (0.98 mmol), alcohols (74 mmol).
Figure6. Plot of conversion within 60 minute reactionfor the acetalization of benzaldehyde with (a, b)
methanol; (c, d) ethanol. Reaction condition: benzaldehyde (0.98 mmol), alcohols (74 mmol ), CoCl250 mg
(0.39 mmol), UiO-66 10 mg, r.t.(28 C).
Figure7. Effect of molecular sizes of benzaldehydes on catalytic activities by UiO-66 and CoCl2. (a)
Benzaldehyde;(b, c) 2-Hydoxybenzaldehyde; and (d, e) 3,5-Di-tert-butyl-2-hydroxybenzaldehyde. Reaction
condition: benzaldehyde (0.98 mmol), methanol (74 mmol), CoCl2 50 mg (0.39 mmol), UiO-66 10 mg, r.t.
(28 C).
Figure8. Recycling studies of the catalyst (a) monitored per 10 minutes and compared with the fresh one, (b)
examined up to 4 runs for 1 h each.
Figure9. FT-IR spectra of fresh UiO-66 and recycled UiO-66.
Figure10. PXRD of fresh UiO-66 and recycled UiO-66.
Table 1. The NBO natural charge of UiO-66 and UiO-67
Natural Charge│e│
No Zr-MOF
Ligand
Zr (0)
Zr (3)
1
2
UiO-66
UiO-67
H2BDC
0.86189 0.86282
H2BPDC 0.85691 0.85769

Table 2. Comparison of UiO-66 with other catalysts in acetalization of benzaldehyde with methanola
Time
(h)
Conversionb
(%)
Entry Catalyst
Remark
1
2
3
4
5
6
7
UiO-66
ZnCl2
1;24
1; 24
1; 24
1
91; 83
40; 39
11; 9
34
This work
This work
This work
This work
Ref [38]
LiTNc
CoCl2
Cu3(BTC)2
Fe(BTC)
Al2(BDC)3
2; 24
2; 24
24
63; 88
49; 71
66
Ref [38]
Ref [38]
aReaction conditions: r.t. (28 C), benzaldehyde (0.98 mmol), methanol 3 mL (74 mmol), catalysts (50 mg).
bDetermined by GC using naphthalene as an internal standard, except for entries 57 (taken from ref. 38).
cLiTN: Anionic interlayer structures of Taeniolite with host cation of Li+ (ref. 54).