Thiourea-functionalized MIL-101(Cr) metal-organic framework as a hydrogen-bond-donating heterogeneous organocatalyst for the Friedel-Crafts alkylation and Biginelli reactions

Article abstract of DOI:10.1016/j.catcom.2019.105905

In the present paper, a functionally diverse thiourea-grafted MOF was fabricated via postsynthetic modification process through complexation of MIL-101(Cr) with pyridine containing thiourea ligand. This new modified material overcomes a significant tenden

Full text of DOI:10.1016/j.catcom.2019.105905

Journal Pre-proof
Thiourea-functionalized MIL-101(Cr) metal-organic framework
as a hydrogen-bond-donating heterogeneous organocatalyst for
the Friedel-Crafts alkylation and Biginelli reactions
Reza Mohammadian, Mostafa M. Amini, Ahmad Shaabani
PII:
S1566-7367(19)30366-8
DOI:
https://doi.org/10.1016/j.catcom.2019.105905
CATCOM 105905
Reference:
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
18 September 2019
10 December 2019
10 December 2019
Please cite this article as: R. Mohammadian, M.M. Amini and A. Shaabani, Thiourea-
functionalized MIL-101(Cr) metal-organic framework as a hydrogen-bond-donating
heterogeneous organocatalyst for the Friedel-Crafts alkylation and Biginelli reactions,
Catalysis Communications (2019), https://doi.org/10.1016/j.catcom.2019.105905
This is a PDF file of an article that has undergone enhancements after acceptance, such
as the addition of a cover page and metadata, and formatting for readability, but it is
not yet the definitive version of record. This version will undergo additional copyediting,
typesetting and review before it is published in its final form, but we are providing this
version to give early visibility of the article. Please note that, during the production
process, errors may be discovered which could affect the content, and all legal disclaimers
that apply to the journal pertain.
© 2019 Published by Elsevier.

Journal Pre-proof
Thiourea-functionalized MIL-101(Cr) metal-organic framework as a
hydrogen-bond-donating heterogeneous organocatalystfor the Friedel-
Crafts alkylation and Biginelli reactions
Reza Mohammadian, Mostafa M. Amini,* Ahmad Shaabani*
Faculty of Chemistry, Shahid Beheshti University, G.C., P.O. Box 19396-4716, Tehran, Iran
*Corresponding authors: Tel: +982129903109, Fax: +982122431663, E-mail address: m-pouramini@sbu.ac.ir;
Tel: +982129902800, Fax: +982122431663 E-mail address: a-shaabani@sbu.ac.ir.
CRediT author statement
Reza Mohammadian: Conceptualization, Methodology, Software, Data curation, Writing-
Original draft preparation, Visualization, Investigation.
Mostafa M. Amini: Supervision, Writing- Reviewing and Editing, Software, Validation.
Ahmad Shaabani: Supervision, Writing- Reviewing and Editing.

Journal Pre-proof
Abstract
In the present paper, a functionally diverse thiourea-grafted MOF was fabricated via
postsynthetic modification process through complexation of MIL-101(Cr) with pyridine
containing thiourea ligand. This new modified material overcomes a significant tendency of
hydrogen-bond-donating (HBD) organocatalysts to undergo self-aggregation and subsequent
decrease in their solubility and reactivity. A double Lewis acid-HBD catalysis activation
mechanism causes the synergistic effect and to some extent has a better performance than the
thiourea ligands and the parent MOF in Friedel-Crafts alkylation and Biginelli reactions.
Keywords: Hydrogen-bonding organocatalysis; Metal-organic framework; Thiourea;
Postmodification; Heterogeneous catalyst
1. Introduction
Hydrogen bonding promoted catalysis has been demonstrated to be an appropriate candidate
to fill a substantial gap between enzyme- and metal-catalysis, due to its great advantages such
as availability, non-hazardous nature, simple handling, and low cost [1]. Of the various
hydrogen-bond-donating (HBD) organocatalysts reported so far [2], those containing thiourea
core are a remarkable achievement of modern synthetic strategies designation [3]. By having
double hydrogen-bonding interactions with the substrates, thiourea catalysts are capable of
promotion of various organic transformations such as Mannich-type reactions [4], Michael
additions [5], Claisen rearrangements [6] and aldol reactions [7] in an asymmetric or racemic
fashion. Although the use of thiourea organocatalysts has received much attention from
organic chemists in recent years, several issues need to be addressed into consideration to
take full advantage of the potential of such catalysts. The first problem is the homogeneous
nature of thiourea which prevents its recyclability, and the second one is dimerization and
oligomerization of thiourea organocatalyst through hydrogen bonding which leads to self-

Journal Pre-proof
quenching phenomenon and significant reduction of its performance (Scheme 1)[8]. With
these features in mind, chemical immobilization of thiourea on support [9, 10] would
overcome these problems and provide a unique opportunity for the efficient utilization of
organocatalyst in various reactions.
Scheme 1. Illustration of homogeneous and heterogeneous thiourea organocatalysts performances.
Metal-organic frameworks (MOFs) as novel hybrid materials are three-dimensional buildings
with infinite network structure from metal ions and multipodal organic linkers [11]. These
novel porous solids have attracted great attention due to their extraordinary chemical and
physical properties including high surface area, well-defined pore structure, and peculiar
chemical environments [12, 13]. So far, a wide variety of MOFs with different chemical
properties and porous structures has been reported in which the majority of them suffer from
limitations in their widespread commercial applications, due to their low framework stability
and high cost [14]. One of the most stable MOFs is MIL-101(Cr), consisting of trimetric
Cr(III) clusters and terephthalic acid with large Langmuir surface area, high thermal, and
chemical stability [15]. One important feature of this type of MOF is its coordinatively

Journal Pre-proof
unsaturated metal sites (CUS) formed by the removal of water coordinated with chromium
atoms, providing Lewis acid centers and postsynthetic functionalization via chelating of
active species [16]. This unique property allows the introduction of various functionalities
into MOF and could be the right solution to heterogenization of homogeneous catalysts,
prevention of self-quenching and self-assembly behavior of organocatalyst and creating
synergistic effects in catalyst performance. In this context and concerning the advantages and
drawbacks mentioned for the thiourea organocatalysis reactions and also in the continuation
of our interest in developing catalytic systems based on MOFs for synthetic methodologies
[17, 18], herein, we report a novel strategy to decoration of thiourea ligands onto the CUS of
MIL-101(Cr). The resulting complexes showed remarkable activities in Friedel-Crafts
alkylation and Biginelli reactions by overcoming recycling, self-quenching and solvation
issues that homogeneous thiourea catalysts are faced with them.
2. Result and discussion
Considering that adsorption of pyridine with an unshared electron pair on the CUS of MIL-
101(Cr) could be accomplished due to the strong interaction between electron donors and
acceptors [15, 19, 20], an attempt has been made to synthesize various thiourea
organocatalyst containing pyridine moieties. Next, several organocatalysts were coordinated
onto the CUS of MIL-101(Cr), and a series of functionalized MOF materials by
coordinatively attaching different thiourea ligands were achieved (Scheme 2).

Journal Pre-proof
Scheme 2. Schematic illustration of heterogeneous thiourea-grafted MIL-101(Cr) catalyst preparation.
2.1. Characterization of MIL-101(Cr)@thiourea catalysts
The FT-IR and XRD analyses were employed to characterize the prepared MIL-101(Cr) and
three different thiourea-grafted MIL-101(Cr) materials. The introduction of thiourea moieties
on MIL-101(Cr) in all three catalysts was supported by FT-IR spectroscopy based on the
-1
appearance of three stretching bands at ~1110, 1500 and 1510 cm , related to CN symmetric
and asymmetric stretching modes. Moreover, grafting of the thiourea on the scaffolds was
also confirmed by the emergence of stretching bands at ~650 cm-1, which is associated with
the C=S bands in all three catalyst spectra (Figure 1). In addition, to show the interaction of
Cr-N bond in the catalyst, FT-IR spectra of MIL-101(Cr) and MIL-101(Cr)@thiourea (3)

Journal Pre-proof
-1
were measured in the 4000-100 cm region using CsCl pellet (Figure S1, ESI†). As can be
seen in Figure S1, the coordination of nitrogen atom of pyridine to the Cr(III) site in MIL-
101(Cr)@thiourea (3) is disclosed by the appearance of two stretching bands at ~310 and 389
cm-1 which is in accordance with the previous reports on the coordination of nitrogen atoms
with Cr(III) centers [21, 22].
650
1500, 1510
Figure 1. FT-IR spectra of MIL-101(Cr) (A), Thiourea (1) (B), Thiourea (2) (C), Thiourea (3) (D), MIL-
101(Cr)@thiourea (1) (E), MIL-101(Cr)@thiourea (2) (F), and MIL-101(Cr)@thiourea (3) (G).
Powder X-ray diffraction (PXRD) analysis was performed on synthesized MIL-101(Cr), and
three thiourea-grafted MIL-101(Cr) catalysts and the results illustrated that all four materials
were in good agreement with the simulated one [23]. These results demonstrated the
successful preparation of MIL-101(Cr) and retention of the basic structure of parent MOF in
the final catalysts after postsynthetic pyridine modification (Figure 2).

Journal Pre-proof
Figure 2. XRD patterns of MIL-101(Cr) (A), MIL-101(Cr)@thiourea (1) (B), MIL-101(Cr)@thiourea (2) (C),
and MIL-101(Cr)@thiourea (3) (D).
At this stage, with the assurance of catalysts formation as confirmed by the FT-IR and PXRD
experiments, the synthesized materials were initially tested in the Friedel-Crafts alkylation
reaction between indole and β-nitrostyrene to choose the most appropriate catalyst with the
highest performance for more characterization. The results of the comparisons in Table 1
showed that MIL-101(Cr)@thiourea (3) has the best performance in the reaction, which
1
maybe is due to the presence of more acidic hydrogens (δ = 11.5-12.5 ppm in H NMR,
ESI†) as a result of the electron-withdrawing groups presence in its structure.
Table 1. Comparison of synthesized thiourea-grafted MIL-101(Cr) materials in the Friedel-Crafts alkylation
reaction between indole and β-nitrostyrenea
Entry
Catalyst
Yieldb (% )
1
2
3
4
MIL-101(Cr)
17
65
53
81
MIL-101(Cr)@thiourea (1)
MIL-101(Cr)@thiourea (2)
MIL-101(Cr)@thiourea (3)
a
Reaction conditions: indole (1 mmol), β-nitrostyrene (1 mmol), CH3CN (7 mL), and catalyst under reflux
conditions for 48 h.
b Isolated yield.

Journal Pre-proof
After finding the most efficient catalyst (MIL-101(Cr)@thiourea (3)), TGA, BET, SEM, and
EDS analyses were performed to complete characterization. The thermal stability of parent
MOF (MIL-101(Cr)) and MIL-101(Cr)@thiourea (3) was assessed by thermogravimetric
analysis (TGA) in air. As Figure S2 (ESI†) shows, the TGA curve of MIL-101(Cr) indicates
o
an initial mass loss at the temperature ranges of ~25-350 C due to the loss of the coordinated
water and solvent molecules in its structure. In the case of MIL-101(Cr)@thiourea (3), a
lower mass loss has occurred in the temperature ranges of ~25-350 °C, which indicates that
water in parent MOF could have been replaced by the thiourea molecules. Both MIL-101(Cr)
o
and MIL-101(Cr)@thiourea (3) represent the second weight loss between ~350-500 C due to
the collapse of the MIL-101(Cr) framework and decomposition of the dicarboxylate linkers.
A higher overall mass loss (~4%) in MIL-101(Cr)@thiourea (3) diagram reflects the presence
of additional organic (thiourea) moieties.
Nitrogen porosimetry experiments of the samples revealed that BET surface areas and total
pore volumes of MIL-101(Cr)@thiourea (3) are substantially decreased in comparison with
parent MOF, due to the thiourea ligands occupying the cavities of the MIL-101(Cr) (Table
S1, ESI†). However, the surface areas of the thiourea functionalized MOF are still larger than
those reported for silicas or zeolites (generally less than 1000 m2/g) [24].
The morphology and nanostructure of the parent MOF and prepared catalyst were visualized
by scanning electron microscopy (SEM) analyses (Figure S3, ESI†). The regular shapes and
monodispersity of the MIL-101(Cr) are visible from Figure S3A. Similar octahedral-shaped
crystals and morphology are also observed from SEM images of MIL-101(Cr)@thiourea (3)
(Figure S3B, C), demonstrating that postsynthetic modification of MIL-101(Cr) by thiourea
did not affect the structural integrity of parent MOF.

Journal Pre-proof
The energy dispersive X-ray spectroscopy (EDS) analysis disclosed the chemical
composition of the final catalyst, and result showed the simultaneous presence of chromium,
sulfur, and nitrogen elements (Figure S4A, ESI†). Furthermore, EDS elemental mapping
demonstrated a homogeneous distribution of the chromium and sulfur in the structure MIL-
101(Cr)@thiourea (3) material (Figures S4B, ESI†). Finally, CHNS analysis of MIL-
101(Cr)@thiourea (3) showed 0.96 mmol.g-1 thiourea loading in the prepared catalyst.
2.2.Catalytic performance of thiourea-functionalized MOF
Due to the importance of tryptamine derivatives, the Friedel-Crafts alkylation of indole via β-
nitrostyrene has received considerable attention [25]. Unfortunately, lower nucleophilicity of
indole causes the Friedel-Crafts reaction became relatively slow. Developing heterogeneous
catalysts, which activates the electrophilic nature of β-nitrostyrene through hydrogen
bonding, is one of the possible solutions to overcome this issue. The catalytic activity of
MIL-101(Cr)@thiourea (3) in the Friedel-Crafts reaction between β-nitrostyrene and indole
as model substrates was evaluated and various parameters such as catalyst loading, reaction
temperature, and reaction medium were optimized (Table 2). At the outset, acetonitrile was
used as a reaction medium, and various amounts of catalyst were explored in the model
reaction. In the absence of the catalyst, no desired product was obtained under reflux
conditions for 24 h (Table 2, entry 1). When the reaction was run in the presence of MIL-
101(Cr)@thiourea (3) (10 mg) at room temperature, only 16% yield was achieved, but by
o
raising the temperature to 80 C, 44% yield was obtained within 48 h (Table 2, entries 2, 3).
The amount of catalyst was optimized to be 30 mg due to a higher yield than the other
catalyst loading (Table 2, entry 5). The model reaction was also tested in the presence of
other catalysts such as thiourea (3) and MIL-101(Cr) to confirm the catalytic efficiency of
MIL-101(Cr)@thiourea (3). The results of the comparisons demonstrated that both catalysts
could partially promote the reaction which maybe is due to the non-solubility of thiourea (3)

Journal Pre-proof
in the reaction medium and the absence of effective active sites in parent MOF (Table 2,
entries 7, 8). Moreover, the physical mixture of MIL-101(Cr) and thiourea (3) with similar
loading of each component (1.00 g of MIL-101(Cr) and 0.50 g of thiourea (3)) under solvent-
free conditions was also tested in the model reaction. The result demonstrated that this
catalyst could not promote the reaction significantly (Table 2, entry 9). This phenomenon can
be attributed to the self-aggregation of thiourea molecules since the physical mixing of MIL-
101(Cr) and thiourea under solvent-free conditions is not able to separate thiourea oligomers
from each other. Finally, screening different solvents revealed that the most suitable reaction
medium is toluene due to a much shorter reaction time (Table 2, entry 12).
Table 2. Optimization of reaction conditions for the Friedel-Crafts alkylation reactiona
Entry
Catalyst (mg)
-
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Temperature (o C)
Time (h)
Yieldb (% )
1
2
3
4
5
6
7
8
reflux
r.t.
24
48
48
48
48
48
48
48
Trace
16
MIL-101(Cr)@thiourea (3) (10)
MIL-101(Cr)@thiourea (3) (10)
MIL-101(Cr)@thiourea (3) (20)
MIL-101(Cr)@thiourea (3) (30)
MIL-101(Cr)@thiourea (3) (40)
MIL-101(Cr) (30)
reflux
reflux
reflux
reflux
reflux
reflux
44
69
81
83
17
Thiourea (3) (30)
29
Physically mixed MIL-101(Cr) and
thiourea (3) (30)
9
CH3CN
reflux
48
24
10
11
12
13
14
15
MIL-101(Cr)@thiourea (3) (30)
MIL-101(Cr)@thiourea (3) (30)
MIL-101(Cr)@thiourea (3) (30)
MIL-101(Cr)@thiourea (3) (30)
MIL-101(Cr)@thiourea (3) (30)
MIL-101(Cr)@thiourea (3) (30)
water
toluene
toluene
toluene
neat
reflux
70
48
24
18
18
48
48
-
76
80
84
reflux
80
85
Trace
53
CH2Cl2
25

Journal Pre-proof
aReaction conditions: indole (1 mmol), β-nitrostyrene (1 mmol), solvent (7 mL), and catalyst.
bIsolated yield.
After optimizing the reaction conditions, the scope of the Friedel-Crafts alkylation reaction
was explored using various nucleophiles and β-nitrostyrene with electron-donating and
withdrawing substitutes (Table S2, ESI†). As shown in Table S2, β-nitrostyrene with
electron-donating groups such as Me and OMe are more reactive in this reaction, and
electron-withdrawing substitute (NO2) did not produce any product. This phenomenon can be
due to the greater ability of the electron donor groups to form hydrogen bonds with the
catalyst in the reaction mechanism. Other nucleophiles such as pyrrole and N,N-
dimethylaniline gave products in moderate to good yields, while acetylacetone and N-methyl-
N-phenylformamide did not proceed the reaction.
Based on published reports on the formation of hydrogen bonding between thiourea and nitro
groups [26], a plausible mechanism for the Friedel-Crafts alkylation of indole with β-
nitrostyrene in the presence of MIL-101(Cr)@thiourea (3) is illustrated in Scheme 3. Initially,
the interaction between β-nitrostyrene and catalyst through the formation of hydrogen
bonding is led to electron deficiency in the C=C double bond of β-nitrostyrene. Next, the
nucleophilic attack of indole to β-nitrostyrene from C3 carbon atom and subsequent 1,3-H
shift are led to the final product.

Journal Pre-proof
Scheme 3. Plausible mechanism for the Friedel-Crafts alkylation of indole with β-nitrostyrene in the presence of
catalyst.
Inspired by the success of reaction mentioned above, and literature reports of catalytic
applications of HBD organocatalysts in the biginelli reaction [27, 28], we decided to extend
the study to examine the efficiency of using of thiourea-grafted MOF catalyst for the
Biginelli reaction (Table S3, ESI†). The best reaction conditions were 30 mg catalyst in
ethanol under reflux condition.
With the optimized conditions established, the scope of the reaction was explored with
different substrates (Table S4, ESI†). As can be seen, also, in this case, the aromatic aldehyde

Journal Pre-proof
with electron donor substituent is more reactive than the one with electron-withdrawing
groups.
To investigate the heterogeneity of the catalyst, hot filtration test was conducted by removing
the catalyst through filtration after ~50% completion of the Friedel-Crafts alkylation of indole
with β-nitrostyrene under specified optimized conditions. The filtrates were further stirred in
the absence of catalyst under the same initial reaction conditions and sampling at different
time intervals revealed no considerable progress was achieved after 24 h.
The reusability of catalyst was explored in four consecutive runs of Friedel-Crafts alkylation
of indole with β-nitrostyrene. Figure S5 (ESI†) represents the catalytic data of reusability
experiments, and as can be seen, the activity of the catalyst is retained up to next three runs
with a slight decrease in the catalytic performance which can be attributed to the loss of
catalyst during the recovery process and somewhat leaching of thiourea moieties from the
catalyst in every catalytic run. For further clarification of the leaching phenomenon, CHNS
analysis of the fresh and 3rd cycle recovered catalysts were carried out (Table S5, ESI†).
Interestingly and unexpectedly, the used catalyst showed higher nitrogen content for the fresh
one in contrast to sulfur, which disclosed the deposition of organic components (product or
unreacted substrates) in the solid. Therefore, the leaching was obtained on the base of sulfur
values in the fresh and used catalyst. On the worth scenario, the amount of leaching was
below 6.5 wt.%.
The stability of the corresponding catalyst during the reactions was supported by comparison
of the PXRD pattern of the recovered catalyst with the fresh one. Figure S6 (ESI†)
demonstrates that no significant changes in the PXRD pattern of recovered catalyst are
visible, and the crystalline nature of it is still retained.

Journal Pre-proof
The catalytic performance of MIL-101(Cr)@thiourea (3) has been assessed in comparison
with other reported heterogeneous HBD organocatalysts in the Friedel-Crafts alkylation
(Table S6, ESI†) [29-31]. The results clearly showed that the activity of MIL-
101(Cr)@thiourea (3) is comparable or even better to some extent than several reported
hydrogen bond donating catalysts due to shorter reaction time. Furthermore, a small amount
of catalyst is sufficient enough to promote the reactions, and the catalyst can be recycled up
to four runs with easy separation and work-up. To the best of our knowledge, this work is the
first report of heterogeneous HBD organocatalyst in the Biginelli reaction. For this reason,
the catalytic performance of MIL-101(Cr)@thiourea (3) was compared with homogeneous
HBD catalysts and MOF catalytic systems [27, 28, 32-34].
3. Conclusions
In summary, a novel functionally diverse thiourea-grafted MOFs as heterogeneous catalysts
were achieved via postsynthetic modification process. The complexation of MIL-101(Cr) and
pyridine containing thiourea ligands resulted in performance superior to that of the ligand or
the parent MOF acting alone in Friedel-Crafts alkylation and biginelli reactions. The
synergistic effect observed in these reactions suggests a double Lewis acid-HBD catalysis
activation mechanism. Future works could be on the path of chiral HBD organocatalyst
grafted MOFs and their application to the asymmetric organic synthesis.
4. Materials and Methods
All reagents were purchased from Sigma-Aldrich and used without further purification. The
β-nitrostyrene derivatives were synthesized according to the previously reported method [35].
The FT-IR spectra were recorded on a Bomem MB-Series FT-IR spectrometer. The X-ray
powder diffraction (XRD) patterns were recorded on an STOE diffract meter with Cu-Kα
radiation (λ = 1.5418 Å). Scanning electron microscopy (SEM) observations were carried out

Journal Pre-proof
with a Philips XL-30 FESEM electron microscope equipped with an energy-dispersive
spectrometer (EDS). All samples were sputtered with gold before the inspection.
Thermogravimetric analysis (TGA) was carried out using STA-1500 instrument at a heating
rate of 10 °C min-1 in the air. Adsorption/desorption isotherm measurement was performed at
77 K (BELSORP-mini II, Japanese). The specific surface areas of the samples were
calculated by the Brunauer-Emmett-Teller method in the P/P0 range of 0.05–0.1. The total
1
pore volume was obtained at the relative pressure (p/p0) of 0.990 in the isotherm. The H
NMR spectra were recorded on a BRUKER DRX-300 AVANCE spectrometer at 300.13
MHz using CDCl3 and DMSO-d6 as solvents and tetramethylsilane (TMS) as an internal
standard. Elemental analysis was performed by an Elementar Analysensysteme GmbH
VarioEL.
Acknowledgements
We gratefully acknowledge financial support from Shahid Beheshti University.
Declaration of interests
The authors declare thatthey have no known competing financial interests orpersonal relationships
that could have appeared to influence the work reported in this paper.
References
[1] M.S. Taylor, E.N. Jacobsen, Asymmetric catalysis by chiral hydrogen‐ bond donors, Angew. Chem., Int.
Ed. 45 (2006) 1520-1543.
[2] A.G. Doyle, E.N. Jacobsen, Small-molecule H-bond donors in asymmetric catalysis, Chem. Rev. 107 (2007)
5713-5743.
[3] X. Fang, C.-J. Wang, Recent advances in asymmetric organocatalysis mediated by bifunctional amine–
thioureas bearing multiple hydrogen-bonding donors, Chem. Commun. 51 (2015) 1185-1197.
[4] M.S. Taylor, N. Tokunaga, E.N. Jacobsen, Enantioselective Thiourea‐ Catalyzed Acyl‐ Mannich Reactions
of Isoquinolines, Angew. Chem., Int. Ed. 44 (2005) 6700-6704.
[5] C.-J. Wang, Z.-H. Zhang, X.-Q. Dong, X.-J. Wu, Chiral amine-thioureas bearing multiple hydrogen bonding
donors: highly efficient organocatalysts for asymmetric Michael addition of acetylacetone to nitroolefins, Chem.
Commun. (2008) 1431-1433.
[6] M. Kirsten, J. Rehbein, M. Hiersemann, T. Strassner, Organocatalytic claisen rearrangement: theory and
experiment, J. Org. Chem. 72 (2007) 4001-4011.

Journal Pre-proof
[7] N. El‐ Hamdouni, X. Companyó, R. Rios, A. Moyano, Substrate‐ Dependent Nonlinear Effects in Proline–
Thiourea‐ Catalyzed Aldol Reactions: Unraveling the Role of the Thiourea Co‐ Catalyst, Chem.: Eur. J. 16
(2010) 1142-1148.
[8] J.V. Alegre-Requena, E. Marqués-López, R.P. Herrera, D.D. Díaz, Metal–organic frameworks (MOFs) bring
new life to hydrogen-bonding organocatalysts in confined spaces, CrystEngComm, 18 (2016) 3985-3995.
[9] Y. Luan, N. Zheng, Y. Qi, J. Tang, G. Wang, Merging metal–organic framework catalysis with
organocatalysis: A thiourea functionalized heterogeneous catalyst at the nanoscale, Catal. Sci. Technol. 4 (2014)
925-929.
[10] A. Puglisi, M. Benaglia, R. Annunziata, J.S. Siegel, Immobilization of chiral bifunctional organocatalysts
on poly (methylhydrosiloxane), ChemCatChem, 4 (2012) 972-975.
[11] M.Y. Masoomi, A. Morsali, A. Dhakshinamoorthy, H. García, Mixed‐ Metal MOFs: Unique Opportunities
in Metal‐ organic Framework Functionality and Design, Angew. Chem., Int. Ed. 58(2019) 15188-15205.
[12] A. Dhakshinamoorthy, A.M. Asiri, H. Garcia, 2D Metal–Organic Frameworks as Multifunctional Materials
in Heterogeneous Catalysis and Electro/Photocatalysis, Adv. Mater. 31 (2019) 1900617.
[13] A. Dhakshinamoorthy, Z. Li, H. Garcia, Catalysis and photocatalysis by metal organic frameworks,
Chem.Soc. Rev. 47 (2018) 8134-8172.
[14] U. Mueller, M. Schubert, F. Teich, H. Puetter, K. Schierle-Arndt, J. Pastre, Metal–organic frameworks-
prospective industrial applications, J. Mater. Chem. 16 (2006) 626-636.
[15] Z.Y. Gu, X.P. Yan, Metal–organic framework MIL‐ 101 for high‐ resolution gas‐ chromatographic
separation of xylene isomers and ethylbenzene, Angew. Chem., Int. Ed. 49 (2010) 1477-1480.
[16] S. Wang, L. Bromberg, H. Schreuder-Gibson, T.A. Hatton, Organophophorous ester degradation by
chromium (III) terephthalate metal–organic framework (MIL-101) chelated to N, N-dimethylaminopyridine and
related aminopyridines, ACS Appl. Mater. Interfaces, 5 (2013) 1269-1278.
[17] R. Mohammadian, M.K. Alavijeh, N. Kamyar, M.M. Amini, A. Shaabani, Metal–organic frameworks as a
new platform for molecular oxygen and aerobic oxidation of organic substrates: Recent advances, Polyhedron,
156 (2018) 174-187.
[18] A. Shaabani, R. Mohammadian, H. Farhid, M.K. Alavijeh, M.M. Amini, Iron-Decorated, Guanidine
Functionalized Metal-Organic Framework as a Non-heme Iron-Based Enzyme Mimic System for Catalytic
Oxidation of Organic Substrates, Catal. Lett. 149 (2019) 1237-1249.
[19] M.J. Kim, S.M. Park, S.-J. Song, J. Won, J.Y. Lee, M. Yoon, K. Kim, G. Seo, Adsorption of pyridine onto
the metal organic framework MIL-101, J. Colloid Interface Sci. 361 (2011) 612-617.
[20] F. Yang, C.-X. Yang, X.-P. Yan, Post-synthetic modification of MIL-101 (Cr) with pyridine for high-
performance liquid chromatographic separation of tocopherols, Talanta, 137 (2015) 136-142.
[21] Y. Saito, J. Takemoto, B. Hutchinson, K. Nakamoto, Infrared studies of coordination compounds
containing low-oxidation-state metals. I. Tris (2, 2'-bipyridine) and tris (1, 10-phenanthroline) complexes, Inorg.
Chem. 11 (1972) 2003-2011.
[22] J. Shirahata, T. Ohori, H. Asami, T. Suzuki, T. Nakayama, H. Suematsu, K. Niihara, Fourier-Transform
Infrared Absorption Spectroscopy of Chromium Nitride Thin Film, Jpn. J. Appl. Phys. 50 (2011) 01BE03.
[23] D. Jiang, A.D. Burrows, K.J. Edler, Size-controlled synthesis of MIL-101 (Cr) nanoparticles with enhanced
selectivity for CO2 over N2, CrystEngComm, 13 (2011) 6916-6919.
[24] G. Férey, C. Mellot-Draznieks, C. Serre, F. Millange, J. Dutour, S. Surblé, I. Margiolaki, A chromium
terephthalate-based solid with unusually large pore volumes and surface area, Science, 309 (2005) 2040-2042.
[25] S. Lancianesi, A. Palmieri, M. Petrini, Synthetic approaches to 3-(2-nitroalkyl) indoles and their use to
access tryptamines and related bioactive compounds, Chem. Rev. 114 (2014) 7108-7149.
[26] G. Dessole, R.P. Herrera, A. Ricci, H-bonding organocatalysed Friedel-Crafts alkylation of aromatic and
heteroaromatic systems with nitroolefins, Synlett, 2004 (2004) 2374-2378.
[27] X.-H. Chen, X.-Y. Xu, H. Liu, L.-F. Cun, L.-Z. Gong, Highly enantioselective organocatalytic Biginelli
reaction, J. Am. Chem. Soc. 128 (2006) 14802-14803.
[28] S. Saha, J.N. Moorthy, Enantioselective organocatalytic Biginelli reaction: dependence of the catalyst on
sterics, hydrogen bonding, and reinforced chirality, J. Org. Chem. 76 (2010) 396-402.
[29] A. Das, N. Anbu, A. Dhakshinamoorthy, S. Biswas, Highly Active Urea-Functionalized Zr (IV)-UiO-67
Metal–Organic Framework as Hydrogen Bonding Heterogeneous Catalyst for Friedel–Crafts Alkylation, Inorg.
Chem. 58 (2019) 5163-5172.
[30] P.C. Rao, S. Mandal, Friedel–Crafts Alkylation of Indoles with Nitroalkenes through
Hydrogen‐ Bond‐ Donating Metal–Organic Framework, ChemCatChem, 9 (2017) 1172-1176.
[31] X.-J. Wang, J. Li, Q.-Y. Li, P.-Z. Li, H. Lu, Q. Lao, R. Ni, Y. Shi, Y. Zhao, A urea decorated (3, 24)-
connected rht-type metal–organic framework exhibiting high gas uptake capability and catalytic activity,
CrystEngComm, 17 (2015) 4632-4636.
[32] I. Suzuki, Y. Iwata, K. Takeda, Biginelli reactions catalyzed by hydrazine type organocatalyst, Tetrahedron
Lett. 49 (2008) 3238-3241.

Journal Pre-proof
[33] S. Rostamnia, A. Morsali, Basic isoreticular nanoporous metal–organic framework for Biginelli and
Hantzsch coupling: IRMOF-3 as a green and recoverable heterogeneous catalyst in solvent-free conditions, RSC
Adv. 4 (2014) 10514-10518.
[34] T.K. Pal, D. De, S. Senthilkumar, S. Neogi, P.K. Bharadwaj, A Partially Fluorinated, Water-Stable Cu (II)–
MOF Derived via Transmetalation: Significant Gas Adsorption with High CO2 Selectivity and Catalysis of
Biginelli Reactions, Inorg. Chem. 55 (2016) 7835-7842.
[35] A. McAnda, K. Roberts, A. Smallridge, M. Trewhella, Mechanism of the yeast mediated reduction of
nitrostyrenes in light petroleum, J. Chem. Soc., Perkin Trans. 1, (1998) 501-504.

Journal Pre-proof
Graphical abstract

Journal Pre-proof
Highlights
 Thiourea moieties were homogeneously decorated on MIL-101(Cr).
 The as-decorated MOF was explored as a heterogeneous organocatalyst.
 The catalyst overcomes the essential shortcomings of homogeneous hydrogen-bond-
donating catalysts.

A double Lewis acid-HBD catalysis activation mechanism creates a synergistic effect
in the reactions.