Design of a Primary-Amide-Functionalized Highly Efficient and Recyclable Hydrogen-Bond-Donating Heterogeneous Catalyst for the Friedel-Crafts Alkylation of Indoles with β-Nitrostyrenes

Article abstract of DOI:10.1021/acscatal.8b04962

A primary-amide-functionalized metal organic framework, {[Zn₂(2-BQBG)(BDC)₂]·10H₂O}_n (1) (in which 2-BQBG = 2,2′-(butane-1,4-diylbis((quinolin-2-ylmethyl)azanediyl))diacetamide and BDC = 1,4-benzenedicarboxylate

Full text of DOI:10.1021/acscatal.8b04962

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Article
Design of a Primary Amide-Functionalized Highly Efficient and
Re-cyclable Hydrogen-Bond-Donating Heterogeneous Catalyst
for the Friedel-Crafts Alkylation of Indoles with #-Nitrostyrenes
DATTA MARKAD, and Sanjay K. Mandal
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b04962 • Publication Date (Web): 25 Feb 2019
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ACS Catalysis
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Design of a Primary Amide-Functionalized Highly Efficient
and Recyclable Hydrogen-Bond-Donating Heterogeneous
Catalyst for the Friedel-Crafts Alkylation of Indoles with -
Nitrostyrenes
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Datta Markad and Sanjay K. Mandal*
Department of Chemical Sciences, Indian Institute of Science Education and Research Mohali, Sector 81, Manauli PO,
S.A.S. Nagar, Mohali, Punjab 140306, INDIA
ABSTRACT: A primary amide-functionalized Metal Organic Framework, {[Zn2(2-BQBG)(BDC)2].10H2O}n (1) (where, 2-BQBG = 2,2'-
(butane-1,4-diylbis((quinolin-2-ylmethyl)azanediyl))diacetamide and BDC = 1,4-benzenedicarboxylate), has been found to be a highly
efficient Hydrogen-Bond-Donating (HBD) heterogeneous catalyst for the Friedel-Crafts alkylation of indole with β-nitrostyrenes under
mild reaction conditions (catalyst loading: 3 mol% and reaction conditions: 12 h and 35 °C). The catalyst can be easily separated from the
reaction mixture by simple filtration for its reuse in four consecutive cycles with a very little loss of activity. More importantly, the one-pot
.
room temperature synthesis of 1 from the self-assembly of Zn(OAc)2 2H2O and 2-BQBG (in CH3OH) and Na2BDC (in H2O) can be easily
scaled-up for obtaining multi-gram quantities in few hours. In order to showcase its versatility, the substrate scope included a variety of
substituted indoles and different β-nitrostyrene derivatives forming the desired products in good to high yields. For its catalytic action, a
direct proof for the key step in the proposed mechanism, based on the interaction of a primary amide group in the 2-BQBG ligand with the
nitro group of β-nitrostyrene through hydrogen bonding, is provided from the enhancement in fluorescence intensity of 1 upon successive
addition of β-nitrostyrene.
KEYWORDS: primary amide-functionalized MOF, Friedel–Crafts alkylation, heterogeneous catalysis, hydrogen-bond-donating,
flexible bis(tridentate) ligand
conjugate addition reactions,18,19 Diels-Alder reactions,20 1,3-
INTRODUCTION
Dipolar cycloaddition reactions,21 Friedel-Crafts reactions.22 In
Metal-organic frameworks (MOFs) are two- and three-
dimensional crystalline materials comprised of metal ions or
inorganic nodes and polytopic neutral and/or anionic organic
ligands/linkers exhibiting rich topological diversity, high surface
area and porosity.1,2 Based on the careful choice of components,
the structure and properties of MOFs can be tuned. This feature,
which is achieved through incorporation of desired functionalities
into MOFs by tailoring the organic ligands and/or linkers, has
allowed their experimental demonstrations of numerous
applications, such as gas storage and separation,3,4 chemical
sensing,5–7 proton conductivity,8,9 water purification,10,11 drug
delivery,12,13 and heterogeneous catalysis, etc.14,15 In particular,
the use of various functional groups incorporated through the
ligands into the framework has been the key to their application in
catalysis.3,16,17
For our interests in designing new organic ligands and
linkers with suitable functional groups for the development of
new MOFs and their application in heterogeneous catalysis,
we have focussed on the biomimetic Hydrogen-Bond-
Donating (HBD) catalysts for the bond-forming reactions as
an alternative to Lewis acid catalysts. Many research groups
have demonstrated the potential of MOFs for catalyzing
general, homogeneous HBD catalysts containing hydrogen
donor sites can significantly undergo self-quenching, which
greatly decreases the catalyst activity. Recently, it was shown
that an incorporation of hydrogen bond donating site into
MOFs can help to avoid such self-quenching of the catalyst.23–
26
The Friedel–Crafts reaction between aromatic compounds
and electron-deficient alkenes has been used widely in
synthetic organic chemistry.27 For example, the reaction of
indole with β-nitroalkenes, such as β-nitrostyrene, is an
important and most widely used reaction towards the synthesis
of indole-based alkaloids, such as physostigmine,28 melatonin
analogues and tryptamine derivatives.22,29 Nitroalkenes, being
active Michael acceptors, have become very important due to
the fact that the nitro derivatives can be transformed into
amino compounds with a variety of different functionalities.30
The reaction of unsubstituted indole with β-nitroalkenes is
slow compared to that of N-alkylated indole, e.g., 1-
methylindole, for poor nucleophilicity of indole.31,32 For
solving this problem, attempts have been made to use various
catalysts, such as organo-catalysts or metallic-catalysts in
homogeneous phase and porous heterogeneous catalysts.24-29,32-
-
numerous C C bond forming transformations, such as
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Thus, a simple, cost-effective and highly efficient catalyst
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39
–
between –NO2 and NH2 moieties has partly encouraged us to
emphasize this, and (iii) the ligand consists of multiple
coordinating groups that are found to be suitable for
constructing extended frameworks with a large surface area,
also favorable for catalysis. All these points have been
summarized for this work in Scheme 1.
1
2
3
4
5
6
7
8
has been the current target for this organic transformation.
In recent years, numerous efforts have been invested in the
development of homogeneous and heterogeneous catalysts
with hydrogen bond donor site for the Friedel-Crafts
alkylation of indole with nitroalkenes.26,27,32,34–44 HBD
catalysts activate electrophilic substrates (e.g., nitroalkene)
toward nucleophiles (e.g., indole) through hydrogen
bonding,38,41 which lowers down the energy of lowest
unoccupied molecular orbital (LUMO) of the electrophiles and
thus favors the nucleophilic attack smoothly. For the synthesis
of such HBD MOF catalysts, an extensive use of many urea,
thiourea and squaramide based ligands with incorporated
hydrogen bond donor sites has flooded the literature.17,24–26,43–50
These ligands in MOFs activate substrates containing a nitro
group through hydrogen bonding toward nucleophilic attack.49
Urea and thiourea incorporated heterogeneous catalysts form a
푅2(8)
Herein, we report the synthesis and crystal structure of a
new MOF with a novel primary amide based ligand (2-BQBG,
Figure 1) viz. {[Zn2(2-BQBG)(BDC)2].10H2O}n (1) (where
BDC = 1,4-benzenedicarboxylate) and its catalytic application
in Friedel-Crafts alkylation reaction of indole and β-
nitrostyrene under mild reaction conditions. To the best of our
knowledge, this is the first report involving a primary amide-
functionalised MOF as a HBD heterogeneous catalyst. Thus,
our work provides insights into the great potential of primary
amide ligand-based MOFs for the design of HBD
heterogeneous catalysis.
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cyclic hydrogen bonded motif
, whereas, squaramide
motif with a nitro group of substrates26,51
2
푅22(9)
Catalytic active site
Catalytic active site
forms
(Scheme 1). However, some of procedures reported for such
catalysts suffer from high catalyst loading, long reaction time,
need of additives48 and multi-step synthesis of catalyst through
post synthetic modification (PSM) or post synthetic exchange
(PSE) of MOFs, 49,50 thus limiting their practical applications.
NH2
H2N
N
O
N
O
Coordinating site
Coordinating site
N
N
Figure 1. Structure of 2,2'-(butane-1,4-diylbis((quinolin-2-
ylmethyl)azanediyl))diacetamide (2-BQBG) with its coordinating
sites and catalytic sites labelled.
Scheme 1. Background and Importance of This Work:
Cyclic Hydrogen Bonded Motifs Formed by the Nitro
Group of Substrates and Urea/Thiourea, Squaramide and
Metal Coordinated Primary Amide Group of the Catalysts
RESULTS AND DISCUSSION
This Work
Previous Work
Synthesis and Characterization. A light yellow solid
2-BQBG ligand was obtained from a two-step process in an
overall yield of 66%. The first step involves a Schiff base
condensation reaction of 2-quinoline carboxaldehyde and 1,4-
diaminobutane (in a 2:1 ratio) in CH3OH and the subsequent
reduction of the intermediate by sodium borohydride. In the
second step, the SN2 reaction between the reduced Schiff base
with 2-bromoacetamide in CH3CN (Scheme S1) occurs. Its
high purity was confirmed by NMR and MS data as well as a
N
O
N
N
O
O
H
O
O
O
H
H
H
N
H
H
N
N
N
N
N
R
R
O
R
R
1
sharp melting point. The FT-IR, H and 13C NMR, and MS
M
X
(LD-TOF) spectra of 2-BQBG are reported in Figures S1-S4
of Supporting Information.
O
O
N
X = O or S
R = Aromatic group
Compound 1 was isolated in 79% yield from a three-
M = Metal ion
.
component self-assembly reaction of Zn(OAc)2 2H2O, 2-
Urea/Thiourea
Squaramide
Primary Amide
BQBG and Na2BDC in a 2: 1: 2 ratio under ambient
conditions. Its formula and phase purity were obtained by
elemental analysis, TGA, FT-IR spectroscopy and X-ray
diffraction (single crystal and powder) analysis. In the FTIR
spectrum of 1 (Figure S5), a strong peak at 1676 cm-1 is
observed for the carbonyl group in 2-BQBG while those at
1580 and 1376 cm−1 correspond to asymmetric and symmetric
stretching frequencies for the carboxylate groups of BDC,
respectively. These values with a difference of 204 cm−1 for
the carboxylate groups are indicative of bis(monodentate)
binding of BDC to Zn(II) as is found in its crystal structure
(vide infra). A clear match between the simulated (generated
from the single-crystal data) and experimental PXRD patterns
of 1 (Figure S6) proves that the single crystals (from the
layering method) and bulk material (from the room
temperature synthesis) are the same. It further confirms the
phase purity of 1. Based on the thermogravimetric analysis
(TGA), the first weight loss (between 30-250 °C) of 15.8%
For developing an efficient catalyst in the Friedel-Crafts
reaction, new ligand, namely, 2,2'-(butane-1,4-
diylbis((quinolin-2-ylmethyl)azanediyl))di-acetamide (2-
a
BQBG), shown in Figure 1, has been designed based on the
following reasons: (i) each of the two primary amide
functionalities in the ligand plays a key role through
coordination of the oxygen atom to a metal center, increasing
-
the acidity of N H bond and creating hydrogen bond donating
environment which may facilitate the catalytic reactions, (ii)
the primary amide sidearm can form a six-membered cyclic
푅2(6)
hydrogen bonded motif
with a nitro group of substrates
2
which is more favorable than forming eight-membered (urea
and thiourea contain) or nine-membered (squaramide contain)
cyclic hydrogen bonded motif; the pioneering studies of Etter52
on the definition of a variety of hydrogen-bonding motifs
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(ca. 16.0%) corresponds to ten lattice water molecules and the summarized in Tables S1 and S2, respectively. Two Zn(II)
1
2
3
4
5
6
7
8
second weight loss (between 250-500 °C) of ~53% (ca.
53.4%) corresponds to ligand (2-BQBG) and linkers (BDC).
This result clearly shows the strong hydrogen bonding of
lattice water molecules with amide functionality as well as
framework stability up to 250 °C. The TGA curve of the
activated 1 (obtained by heating at 120 °C under vacuum for 5
h) does not show any weight loss up to 250 °C indicating the
absence of lattice water molecules (Figure S7). Furthermore,
the PXRD pattern for the activated 1 (Figure S6) matches with
that of 1 indicating the retention of its structural integrity upon
the loss of lattice solvent.
centers connected by the BDC linker are separated by 10.950
Å whereas those connected by the spanning ligand (2-BQBG)
are separated by 8.164 Å. Based on this connectivity, six Zn
centers that form a cavity with a dimension of 19.023 Å x
6.517 Å (distances between two BDC linkers on opposite
sides) adopt a chair conformation, extending to a trans-
decaline type 2D polymer structure (Figure 2, right and Figure
S9). Two 2D sheets in 1 are further connected via moderate π–
π interactions54 between the quinoline rings (centroid–centroid
distances are 3.719 Å and 3.808 Å) to form a 3D
supramolecular assembly (Figure 3, left). Furthermore, as
shown in Figure 3 (right) the topological analysis of 1 reveals
that it has a uninodal 3-connected net (topology: hcb and
Schläfli point symbol: {63}).55,56
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Structural Description. Based on the single-crystal X-
ray diffraction analysis, 1 crystallizes in the triclinic space
1
group P and has a 2D coordination polymer structure. One
Catalysis Studies. Prior to its use, 1 was fully activated
under vacuum (120 oC, 5 h) to remove the lattice water
molecules and provide accessible active sites for substrates.
Zn(II) ion, one BDC, half of 2-BQBG ligand and five lattice
water molecules are present in the asymmetric unit. Each
Zn(II) center adopts a pentacoordinated square pyramidal
geometry, based on the value of  parameter 0.194 (Figure S8,
left), with an N2O3 environment and is surrounded by one
oxygen and two nitrogen atoms of 2-BQBG ligand and two
carboxyl oxygen atoms from two different BDC linkers
(Figure 2 (left) and Figure S8 (right)). The Zn−N1(quinoline)
distance (2.129(5) Å) is shorter than Zn−N2(alkyl) distance
(2.154(5) Å). The two Zn−Ocarb distances are found to be
almost similar, Zn−O2 (2.007(4) Å) and Zn−O4 (1.954(4) Å),
and are in similar range reported in the literature.53
Crystallographic data along with structure refinement
parameters, and selected bond distances and angles are
For assessing the catalytic activity of
1 as a solid
heterogeneous catalyst in the Friedel-Crafts reaction of indole
with β-nitrostyrene, the formation of product was analyzed by
1
1H NMR spectroscopy. Both H NMR spectra and relevant
calculation for the conversion of this transformation by
catalyst 1 are presented in Figure S10. In order to establish the
optimized reaction conditions, the catalytic performance of 1
was assessed in the presence of various solvents as well as
without solvent at room temperature (27 °C) using 3 mol%
(2.8 mg) of 1 for 24 h (Table 1, entries 1-6). The reaction rate
was found to be solvent dependent in the following order with
O
NH2
O
O
N
Zn
N
O
O
N
N
O
O
Zn
O
O
H2N
O
Figure 2. Left: Schematic representation of the coordination environment of Zn(II) in 1. Right: 2D sheet of the 1 in the crystallographic ab
plane.
Figure 3. Left: A 3D supramolecular assembly formed between the 2D sheets in 1 (π-π interactions between the 2D layers are represented
by blue arrows). Right: Node-and-linker-type representation showing AB-AB stacked 2D sheets of 1 (color codes: zinc nodes = green, BDC
linkers = red and 2-BQBG ligands = blue).
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Table 1. Optimization of Reaction Conditions for the The catalytic activity was also compared under identical
1
2
3
4
5
6
7
8
Friedel-Crafts Alkylation Reaction of Indole and β-
conditions without 1 and each component used for making 1,
i.e., Zn(OAc)2 2H2O, 2-BQBG and H2BDC (Table 1, entries
.
Nitrostyrenea
17-20). Interestingly, there was no reaction at all in the
absence of catalyst while a very low conversion (5.6%) in the
HN
NO2
Catalyst
presence of H2BDC was observed. With 2-BQBG,
a
+
NO2
N
H
conversion of 29% was observed after 12 h. The improved
activity of 1 suggests that it prevents primary amide self-
aggregation, which is likely responsible for the sluggish
activity of the free 2-BQBG ligand. This clearly shows the
importance of coordination of the carbonyl group of 2-BQBG
0.15 mmol
0.1 mmol
TONc
21
28
04
09
20
19
33
33
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25
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02
00
9
Entry
1
Time
(h)
Temp
(°C)
Solvent
CHCl3
CH2Cl2
Toluene
CH3CN
CH3OH
neat
Catalyst
mol (%)
Yield
(%)b
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to the Zn(II) center promoting the increase in acidity of N H
24
24
24
24
24
24
24
12
10
8
27
27
27
27
27
27
35
35
35
35
35
35
35
35
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35
35
35
35
35
3
62
83
12
26
60
58
100
100
83
76
63
58
46
30
11
10
29
10
6
bond and creating hydrogen bond donating environment more
favourable (vide supra). In order to support our hypothesis, we
have made two more derivatives of 1 in 77-79% yield
following its synthesis procedure: one with a –C(O)NEt2
group to show an effect of N-H groups ({[Zn2(2-
Et2BQBG)(BDC)2].4H2O}n (1a) (where, 2-Et2BQBG = 2,2'-
2
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
---
3
4
(butane-1,4-diylbis((quinolin-2-ylmethyl)
diethylacetamide)) and the other with a pyridyl group to show
an effect of the carbonyl group ({[Zn2(2-
QPBN)(BDC)2].7H2O}n (1b) (where, 2-QPBN
N',N''-
azanediyl))bis(N,N-
5
6
=
bis(pyridin-2-ylmethyl)-N',N''-bis(quinolin-2-ylmethyl)butane-1,4
-di-mine) (Scheme S2 and Figure S12 and S13). Under the
same catalysis conditions, only 11% and 10% conversions
were obtained for 1a and 1b, respectively (Table 1, entry 15
and 16; Figure S14 and S15). This observation unequivocally
confirms the novelty of the primary amide groups in 1. On the
other hand, only 10% of product formation was observed
7
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
8
9
10
11
12
13
14
15
16
17
18
19
20
.
using Zn(OAc)2 2H2O (Figure S16).
6
Based on the results presented in Table 1 and discussed
above, the substrate scope for 1 with indole and various β-
nitrostyrene derivatives was expanded under the optimized
reaction conditions (Table 2). As expected, β-nitrostyrenes
containing electron-donating or electron-withdrawing groups
could undergo the desired transformation to result the
corresponding alkylated product with satisfactory conversions
(Figure S17 and S18).
4
2
1
12
12
12
12
12
12
Next, the substituents on the indolyl scaffold were also
considered (Table 3). The catalytic efficiency of 1 varied
significantly for differently substituted indoles. A slight
decrease in yield (95%) for 2-methylindole is due to the steric
factor. In order to prove this point, the 2-phenyl substituted
substrate was used where the yield further reduced to 88%.
The electron rich indoles, such as 5-methyl-indole and 5-
methoxy-indole, resulted in the respective products in 100%
yield. This is consistent with the fact that electron-donating
methyl or methoxy groups facilitates activation of the indole
ring towards the nucleophilic attack. On the other hand, an
electron withdrawing group bearing indole, such as 5-chloro-
indole, results in 72% yield of the corresponding product.
More importantly, N-alkylated indole gave dramatically
decreased yield (41%) versus the free indole. This result
clearly supports our proposed mechanism (discussed below)
validating an interaction of N-H group with the catalyst
(Figure S19). Overall, these results demonstrate that 1 is a
heterogeneous, efficient and recyclable catalyst for the
Friedel–Crafts reaction.
No
reaction
aEntries 1-14 were performed using catalyst 1. Entries 15 and 16
were performed using catalyst 1a and 1b, respectively. Entries 17-
19 were performed in presence of 2-BQBG, Zn(OAc)2 2H2O and
H2BDC, respectively. Entry 20 was carried out without any
catalyst. bDetermined by 1H NMR spectroscopy. cNumber of
moles of product per mole of catalyst.
.
respect to conversion: dichloromethane (83%) > chloroform
(62%) > methanol (60%) > acetonitrile (26%) > toluene (12%).
Using dichloromethane as the solvent, the reaction was then
performed with an increase in temperature to 35 °C to obtain
100% conversion in 24 h (Table 1, entry 7). On the other hand,
the reaction was found to be time dependent where a significant
decrease in the conversion was observed for less time (Table 1,
entries 8-14). A plot of % conversion vs time presented in Figure
S11 depicts this trend. Thus, the optimized conditions were found
to be as follows: 3 mol% catalyst, CH2Cl2, 35 °C and 12 h.
Compared to the MOFs reported in the literature, which act as
HBD catalysts for this kind of reaction,24,26,45–48 the efficiency of
catalyst 1 is noteworthy (Table 4) in terms of reaction time,
catalyst loading, solvent, temperature, yield and recyclability
(vide infra). A urea-derived post-modified 3D MOF, Cr-MIL-
101-UR324 boosted the reaction yield up to 93% with 15 mol%
catalyst in 24 h at 60 °C (solvent: acetonitrile). Another hydrogen-
4
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1
2
Table 2. Substrate Scope of β-Nitrostyrene in the Friedel-
Crafts Alkylation Reaction Catalysed by 1
Table 3. Substrate Scope of Indole in the Friedel-Crafts
Alkylation Reaction Catalysed by 1
R1
3
4
5
HN
HN
NO2
3 mol% catalyst
NO2
3 mol% catalyst
R1
+
+
NO2
N
H
O2N
N
H
12 h, 35 °C, CH2Cl2
12 h, 35 °C, CH2Cl2
R
6
0.15 mmol
0.1 mmol
0.15 mmol
0.1 mmol
R
7
8
9
Yielda
(%)
Yielda
(%)
TONb
Entry
1
R1
Product
TONb
Entry
1
R
Product
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HN
HN
H3C
O2N
2-CH3
2-Ph
95
88
32
29
33
33
H
100
71
33
NO2
HN
Ph
O2
HN
2
3
4
N
2
3
4
4-OCH3
4-CH3
4-F
24
25
18
NO2
H3CO
H3C
F
HN
CH3
5-CH3
5-OCH3
100
100
O2
N
HN
76
NO2
HN
OCH3
O2N
HN
53
NO2
HN
Cl
5
6
5-Cl
72
41
24
14
O2N
HN
H3C
5
6
7
4-Cl
4-Br
95
96
80
32
32
27
NO2
NO2
NO2
N
1-CH3
Cl
O2N
HN
aDetermined by 1H NMR spectroscopy. bNumber of moles of
product per mole of the catalyst.
Br
bond-donating squaramide moiety incorporated in UiO-67 MOF
is also inferior to catalyst 1, even after the use of deuterated
solvents.26 Very recently, a solvothermally synthesized urea
functionalized Cu(II) 2D MOF, catalyzed this reaction up to 98%
yield at 60 °C in 18 h (solvent: acetonitrile).45 Furthermore, using
a high loading (22 mol%) of a Zn(II) 3D MOF of 4,4’-ureylene-
benzene dicarboxylate about 90% product was obtained
(toluene/24 h/60 °C).46 Similarly, a postsynthetic exchanged urea
functionalized Cu(II) MOF by Cohen et al. afforded good yield47
(conditions: 5 mol% catalyst, 24 h at 50 °C in chloroform).
Interestingly, Scheidt et al. employed a large amount of Lewis
acid (trimethylsilyl chloride, 18 mol%) to enhance catalytic
activity of urea-based Zn(II) MOF (NU-GRH-1)48 to get 98%
yield (conditions: 3 mol% catalyst, 4 h at 60 °C and toluene-d8 as
solvent). Furthermore, catalyst 1 is synthesized from readily
available and cheap starting materials under ambient conditions,
providing added advantages over other expensive catalysts.
A leaching experiment for 1 was performed to prove its
heterogeneous nature in the reaction between indole and β-
nitrostyrene. As shown in Figure S11, the progress of reaction
was measured after 1 h, and then 1 was removed via filtration.
Upon following the progress of reaction for another 11 h, it was
evident that the removal of catalyst from the reaction mixture
halted the formation of product. Thus, 1 is needed for the
promotion of this reaction. Additionally, after the separation of 1
from the reaction, the filtrate was evaporated to dryness to
determine the amount of zinc in it by EDX. There was no Zn
detected (Figure S20). These results clearly indicate that the
HN
4-NO2
O2N
HN
8
9
2-Br
95
62
32
21
NO2
Br
HN
2-NO2
NO2
NO2
HN
NO2
10
11
3-F
95
96
32
32
F
HN
NO2
3- OCH3
OCH3
aDetermined by 1H NMR spectroscopy. bNumber of moles of
product per mole of the catalyst.
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active species is not leached into product, which is a strong
evidence for the heterogeneous nature of the reaction.
interacts with the nitro group of the β-nitrostyrene through
1
2
3
4
5
6
7
8
hydrogen bonding, increasing the electrophilic character of the
aliphatic carbon atom, and thus favoring the attack from the
indole. Similarly, the interaction of an indole (N-H group)
with 1 not only increases the nucleophilicity but also brings
two substrates efficiently close for the formation of the
alkylated product (Figure 4). In order to support the
mechanism, we studied the interaction of β-nitrostyrene with 1
through fluorescence spectroscopy. A finely ground sample of
1 was used for facilitating close contact between the host
framework and β-nitrostyrene in the sensing experiment. For
investigating its luminescent properties, 2 mg of 1 was well
dispersed in dichloromethane (2 mL) placed in a cuvette by
stirring for 10 minutes. To the stable suspension of 1, a freshly
prepared β-nitrostyrene solution (1 mM in dichloromethane)
was incrementally added. As shown in Figure 4b, 1 shows
enhancement in fluorescence (at 396 nm) upon successive
addition of a β-nitrostyrene (20 µL each time) solution (ex=
315 nm). However, with an incremental addition of indole to 1
did not show such noticeable change in intensity (Figure S24).
One of the advantages of heterogeneous catalysts is its
reusability. Based on the performance of 1 under the optimized
reaction conditions up to four cycles, its reusability has been
found to be very good with a very little loss in its activity (Figure
S21). During the recycling of 1, its loss actually caused a slight
decrease in yield. Comparing the PXRD patterns of fresh and
recovered catalyst, it is clear that 1 does not lose its crystallinity
during the reaction (Figure S22). Furthermore, FT-IR spectra and
solid-state UV-Visible spectra of fresh and recovered catalyst
(after four cycles) showed no significant changes (Figure S23).
Its high catalytic activity can be explained through a
proposed mechanistic cycle, where the ligand containing a
primary amide sidearm of 1 forms a six-member cyclic
푅2(6)
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hydrogen bonded motif
This is more favorable than
with nitro group of substrates.
푅2(8) 푅2(9)
2
or
cyclic hydrogen
2
2
bonded motif formed by urea/thiourea and squaramide based
catalysts, respectively. In addition, 1 has two primary amide
functionality which increases the rate of reaction. In the
catalytic process it is assumed that the primary amide group
(a)
(b)
1
Addition of -nitrostyrene to catalyst
HN
NO2
N
N
O
H
O
H
H
O
N
N
O
O
O
O
Zn
N
O
N
O
N
Zn
O
O
N
O
H
H
Figure 4. (a) Proposed mechanism of the Friedel-Crafts alkylation reaction between indole and β-nitrostyrene catalyzed by 1. (b) Change
in emission spectrum of 1 (dispersed in dichloromethane) upon incremental addition of a solution of β-nitrostyrene in dichloromethane (1
mM).
Table 4. Comparison of Various HBD Catalysts in the Friedel-Crafts Alkylation Reaction of Indole and β-nitrostyrenea
Entry
1
Catalyst
Mol (%)
15
Time (h)
24
Solvent
CH3CN
Temp (oC)
Yield (%)
93
Ref.
24
Cr-MIL-101-UR3
60
26
26
45
2
3
4
Uio-67-Squar/bpdc
Uio-67-Squar/bpdc
[CuL1·H2O].2DMF·H2O
10
10
1.5
24
24
18
24
24
4
CD2Cl2
Toluene-d8
CH3CN
RT
50
60
78
95
98
46
47
48
5
6
7
8
[Zn4O(L2)(DMF)2]·3DMF
Cu4(dbda)2 (CH3OH)4
NU-GRH-1 + TMS-Cl (18 mol%)
{[Zn2(2-BQBG)(BDC)2].10H2O}n
22
5
3
Toluene
CHCl3
Toluene-d8
60
50
60
35
90
>99
98
.
3
12
CH2Cl2
100
This work
aH4dbda = 5,5’-(3,4-dioxocylcobut-1-ene-1,2-diyl)bis(azanediyl)diisophthalic acid, L1 = 5-(3-phenylureido)-benzene-1,3-di(4-phenylcarbo
xylate), L2 = 4,4’-ureylene-benzene dicarboxylate.
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ACS Catalysis
Synthesis of 2,2'-(butane-1,4-diylbis((quinolin-2-
CONCLUSION
1
ylmethyl)azanedi-yl))diacetamide (2-BQBG). It is
prepared in two steps where N,N’-bis(quinolin-2-
ylmethyl)butane-1,4-diamine, 2-BQBD, is an intermediate.
Step 1, Synthesis 2-BQBD: To a methanolic solution of 2-
quinolinecarboxaldehyde (3.14 g, 20 mmol; 10 mL methanol)
In summary, we demonstrated the novelty of a MOF
{[Zn2(2-BQBG)(BDC)2].10H2O}n (1), based on a spanning
ligand with primary amide groups, in a hydrogen bond
donating heterogeneous catalysis. Its performance in the
Friedel–Crafts alkylation of indoles with various β-
nitrostyrenes was found to be much better than other
heterogeneous catalysts reported so far in the literature. In
particular, an improvement in its catalyst loading over MOFs
with secondary amide groups (3 mol% vs 15 mol%,
respectively) supported the importance of binding of the
primary amide oxygen atom with Zn, enhancing the acidity of
N-H bonds to create stronger hydrogen bond donating
environment in the catalysis process. Its broad substrate scope
included six substituted indoles and eleven substituted β-
nitrostyrenes (2-, 3- or 4-substituted with both electron
donating and electron withdrawing groups). Moreover, the
loss of activity of 1 is very little after four consecutive cycles.
Based on two derivatives of catalyst 1, the importance of the
primary amide groups in it was further shown through drastic
decrease in product yields. For its catalytic action, a direct
proof for the key step in the proposed mechanism - the
interaction of a primary amide group in the 2-BQBG ligand
with the nitro group of β-nitrostyrene through hydrogen
bonding - was provided from the enhancement in fluorescence
intensity of 1 upon successive addition of β-nitrostyrene. Due
to the combined contributions of the ordered 2D structure and
highly accessible catalytic active sites, this work with catalyst
1 therefore not only depicts MOFs as a new type of
multifunctional catalysts but also provides a new perspective
for developing highly efficient and robust heterogeneous
catalysts promoting reactions via a hydrogen bond donating
functionality. Further studies toward the design and synthesis
of more rigid primary amide-based MOF catalysts are
underway in our laboratory.
2
3
4
5
6
7
8
9
placed in
a 50 mL two-neck RBF under dinitrogen
atmosphere, 1,4-diaminobutane (1 mL, 10 mmol) was added at
room temperature in a dropwise manner. Upon stirring the
mixture for 4 h, the resulting yellow solution was then reacted
with an excess of sodium borohydride (1.14 g, 1.5 equiv.) at 0
°C. The reaction mixture was stirred further for another 6 h. A
light yellow semi-solid was isolated from the reaction mixture
by extracting with chloroform followed by drying with
anhydrous MgSO4 and removal of solvent under vacuum.
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46
47
48
49
50
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53
54
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60
1
Yield: 3.53 g (96%). H NMR (400 MHz, CDCl3, δ ppm): δ
8.01-8.08 (4H, m), 7.75 (2H, d), 7.66 (2H, d), 7.43 (4H, m),
4.06 (4H, s), 2.70 (4H, m), 1.63 (4H, m). Selected FT-IR
peaks (KBr, cmˉ1): 3350 (br), 2936 (m), 2856 (m), 1595 (s),
1573 (s), 1474 (m), 1438 (m), 1310 (m), 1119 (m), 1050 (s),
1001 (s), 763 (s), 635 (m).
Step 2, To a solution of 2-BQBD (740 mg, 2 mmol; 10 mL
dry acetonitrile) placed in a 50 mL RBF, solid K2CO3 (5.52 g,
40 mmol) was added through a funnel at once and the mixture
was stirred for 30 minutes under N2 atmosphere.
Subsequently, the dropwise addition of 2-bromoacetamide
(555 mg, 4 mmol; dry 15 mL acetonitrile) to it was carried
out. Upon refluxing the mixture for 12 h, it was cooled to
room temperature and filtered through a G-4 crucible to
collect the liquid phase (10 mL x 2 methanol was used to wash
the solid). A solid residue that was obtained upon evaporation
of solvents was re-dissolved in dry methanol. After removal of
redundant K2CO3 and KBr (by-product) via filtration,
methanol was evaporated under vacuum to get an oily
substance. The desired product as a light yellow solid was
obtained by dissolving the oily substance in 10 mL CHCl3 at 0
°C followed by filtration and evaporation of the solvent.
EXPERIMENTAL SECTION
1
Yield: 695 mg (72%). H NMR (400 MHz, CDCl3, δ ppm):
8.12 (2H, d), 7.99 (2H, d), 7.82 (2H, d), 7.72 (2H, t), 7.55 (2H,
t) 7.35 (2H, d), 3.90 (4H, s), 3.19 (4H, s), 2.56 (4H, m), 1.48
(4H, m). 13C NMR (100 MHz, CDCl3, δ ppm): 25.00, 55.61,
58.47, 61.71, 120.77, 126.52, 127.33, 127.65, 128.98, 129.82,
136.79, 147.71, 159.05, 174.73. Selected FT-IR peaks (KBr,
cmˉ1): 3375 (s), 3182 (m), 2943 (m), 1654 (s), 1590 (m), 1405
(m), 1342 (m), 1121 (m), 989 (m), 757 (m), 544 (w). M.P.:
162-164 °C. MS (LD-TOF): m/z calcd. for [(2-BQBG)K]+,
523.221; found, 523.222.
General Methods. All chemicals and solvents that were
obtained from commercial sources were used without further
purification. All reactions were carried out under aerobic
conditions. 1H and 13C NMR spectra of 2-BQBD and 2-BQBG
were obtained in CDCl3 at 25 °C on a Bruker ARX-400
spectrometer, where chemical shifts are reported relative to the
residual solvent signals. Thermogravimetric analysis was
carried out from 25 to 500 °C (at a heating rate of 10 °C/min)
under dinitrogen atmosphere on a Shimadzu DTG-60H
instrument. The elemental analysis (C, H, N) was carried out
using a Leco TruSpec Micro analyzer. FT-IR spectra were
measured in the 4000-400 cm-1 range on a Perkin-Elmer
Spectrum I spectrometer with samples prepared as KBr
pellets. Solid state UV-Vis spectra were recorder on Agilent
Technologies Cary series (Cary–5000) UV-Vis-NIR
spectrophotometer. Melting points were determined with a
Büchi M-565. For catalyst leaching during the reaction, the
amount of Zn was estimated by Energy Dispersive X-ray
spectroscopy (EDX, HORIBA EX-250, 15 kV). Powder XRD
data were recorded on a Rigaku Ultima IV diffractometer,
which was described earlier from this laboratory, with a 2-
theta range between 5° to 50° with a scanning speed of 2° per
minute with a 0.01° step. For the single crystal X-ray
diffraction study, see details in the Supporting Information.
Synthesis of {[Zn2(2-BQBG)(BDC)2].10H2O}n (1).
.
Using a 10 mL RBF, Zn(OAc)2 2H2O (22.7 mg, 0.10 mmol)
and 2-BQBG (25 mg, 0.05 mmol) were dissolved in CH3OH
(3 mL) and disodium-1,4-benzenedicarboxylate (17 mg, 0.10
mmol; 2 mL water) was subsequently added, leading to the
formation of a white precipitate. After stirring it at room
temperature for 4 h, an off-white solid was isolated in dry
form by washing it with methanol under vacuum. Yield: 44
mg (79%). Anal. Calcd. (%) for C44H60N6O20Zn2 (MW
1123.7): Calc. C, 47.03; H, 5.38; N, 7.48. Found: C, 46.70; H,
5.73; N, 7.69. Selected FT-IR peaks (KBr, cm-1): 3350 (br),
1676 (s), 1580 (s), 1376 (s), 1135 (m), 1202 (w), 826 (m), 801
(m), 744 (s), 689 (s). In a thin test tube, single crystals of 1
.
were grown as follows: a clear solution of Zn(OAc)2 2H2O (9
mg, 0.041 mmol) and 2-BQBG (10 mg, 0.020 mmol)
dissolved in 0.8 mL of C2H5OH/H2O (1:1, v/v) was layered
with a solution of disodium-1,4-benzenedicarboxylate (6.6
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(4) Li, B.; Wen, H.-M.; Zhou, W.; Chen, B. Porous Metal–Organic
Frameworks for Gas Storage and Separation: What, How, and Why? J.
Phys. Chem. Lett. 2014, 5, 3468–3479.
(5) Kreno, L. E.; Leong, K.; Farha, O. K.; Allendorf, M.; Van Duyne,
R. P.; Hupp, J. T. Metal–Organic Framework Materials as Chemical
Sensors. Chem. Rev. 2012, 112, 1105–1125.
mg, 0.041 mmol) in 0.8 mL H2O, keeping a middle layer of
0.2 mL of C2H5OH/H2O (1:1, v/v). Colourless needle shaped
crystals that were obtained after four days were found to be
suitable for single crystal X-ray diffraction.
1
2
3
4
5
6
7
8
General protocol used for the Friedel-Crafts reaction.
Indole (18 mg, 0.15 mmol), β-nitrostyrene (15 mg, 0.1 mmol),
and 3 mol% (2.8 mg) of 1 were added to 200 µL of CH2Cl2 in
a 5 mL glass screw cap vial. The reaction mixture was stirred
at 35 °C for 12 h. After cooling to room temperature, the
reaction mixture was filtered, washed with 0.5 mL CH2Cl2 and
solvent was evaporated under vacuum to get a dry product. To
(6) Zhang, M.; Feng, G.; Song, Z.; Zhou, Y.-P.; Chao, H.-Y.; Yuan, D.;
Tan, T. T. Y.; Guo, Z.; Hu, Z.; Tang, B. Z.; Liu, B.; Zhao D. Two-
Dimensional Metal–Organic Framework with Wide Channels and
Responsive Turn-On Fluorescence for the Chemical Sensing of Volatile
Organic Compounds. J. Am. Chem. Soc. 2014, 136, 7241–7244.
(7) Hu, Z.; Deibert, B. J.; Li, J. Luminescent Metal–Organic
Frameworks for Chemical Sensing and Explosive Detection. Chem. Soc.
Rev. 2014, 43, 5815–5840.
(8) Bureekaew, S.; Horike, S.; Higuchi, M.; Mizuno, M.; Kawamura,
T.; Tanaka, D.; Yanai, N.; Kitagawa, S. One-Dimensional Imidazole
Aggregate in Aluminium Porous Coordination Polymers with High Proton
Conductivity. Nat. Mater. 2009, 8, 831–836.
(9) Shigematsu, A.; Yamada, T.; Kitagawa, H. Wide Control of Proton
Conductivity in Porous Coordination Polymers. J. Am. Chem. Soc. 2011,
133, 2034–2036.
(10) Wang, C.; Liu, X.; Chen, J. P.; Li, K. Superior Removal of
Arsenic from Water with Zirconium Metal-Organic Framework UiO-66.
Sci. Rep. 2015, 5, 16613.
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this 400 µL CDCl3 was added for H NMR analysis. The
reaction was monitored by 1H NMR spectroscopy via the
integration of α-vinyl and β-vinyl proton of β-nitrostyrene (δ
8.01 - 8.06 ppm) and the resulting aliphatic proton of the
product 3-(2-nitro 1-phenylethyl)-1H-indole (δ 4.92 - 5.25
ppm). In order to perform the catalyst recycling experiments,
the used catalyst (separated by centrifugation and filtration)
was washed with MeOH and dried under vacuum. It was then
reused for the next run of the reaction as described above.
(11) Hasan, Z.; Jhung, S. H. Removal of Hazardous Organics from
Water Using Metal-Organic Frameworks (MOFs): Plausible Mechanisms
for Selective Adsorptions. J. Hazard. Mater. 2015, 283, 329–339.
(12) Ke, F.; Yuan, Y.-P.; Qiu, L.-G.; Shen, Y.-H.; Xie, A.-J.; Zhu, J.-
F.; Tian, X.-Y.; Zhang, L.-D. Facile Fabrication of Magnetic Metal–
organic Framework Nanocomposites for Potential Targeted Drug
Delivery. J. Mater. Chem. 2011, 21, 3843–3848.
(13) Horcajada, P.; Serre, C.; Maurin, G.; Ramsahye, N. A.; Balas, F.;
Vallet-Regí, M.; Sebban, M.; Taulelle, F.; Férey, G. Flexible Porous
Metal-Organic Frameworks for a Controlled Drug Delivery. J. Am. Chem.
Soc. 2008, 130, 6774–6780.
(14) Jiang, H.-L.; Xu, Q. Porous Metal–organic Frameworks as
Platforms for Functional Applications. Chem. Commun. 2011, 47, 3351–
3370.
(15) Lee, J.; Farha, O. K.; Roberts, J.; Scheidt, K. A.; Nguyen, S. T.;
Hupp, J. T. Metal–organic Framework Materials as Catalysts. Chem. Soc.
Rev. 2009, 38, 1450–1459.
(16) Valvekens, P.; Vermoortele, F.; De Vos, D. Metal–organic
Frameworks as Catalysts: The Role of Metal Active Sites. Catal. Sci.
Technol. 2013, 3, 1435–1445.
(17) Chughtai, A. H.; Ahmad, N.; Younus, H. A.; Laypkov, A.;
Verpoort, F. Metal–organic Frameworks: Versatile Heterogeneous
Catalysts for Efficient Catalytic Organic Transformations. Chem. Soc.
Rev. 2015, 44 , 6804–6849.
(18) Li, H.; Wang, Y.; Tang, L.; Deng, L. Highly Enantioselective
Conjugate Addition of Malonate and β-Ketoester to Nitroalkenes:
Asymmetric C−C Bond Formation with New Bifunctional Organic
Catalysts Based on Cinchona Alkaloids. J. Am. Chem. Soc. 2004, 126,
9906–9907.
(19) Malerich, J. P.; Hagihara, K.; Rawal, V. H. Chiral Squaramide
Derivatives Are Excellent Hydrogen Bond Donor Catalysts. J. Am. Chem.
Soc. 2008, 130, 14416–14417.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acscatal.0000000
Synthesis of compounds 1a and 1b, FT-IR spectra,
PXRD patterns, TGA thermograms, NMR spectra,
Mass spectrum, EDX analysis, Solid state UV-Vis
spectra, NMR calculations, Emission spectrum (Figures
S1−S24, Scheme S1-S2 and Tables S1-S2) (PDF)
X-ray crystallographic data for 1 in CIF format (CCDC
No. 1860145) (CIF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: sanjaymandal@iisermohali.ac.in
ORCID
Sanjay K. Mandal: 0000-0002-5045-6343
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
IISER, Mohali provided the financial assistance for this work. D.
M. is grateful to the UGC, India, for a research fellowship. The
central facilities (X-ray, NMR and SEM) and other departmental
facilities at IISER Mohali are acknowledged. We also thank an
anonymous reviewer for his suggestions.
(20) Rajaram, S.; Sigman, M. S. Design of Hydrogen Bond Catalysts
Based on
a Modular Oxazoline Template: Application to an
Enantioselective Hetero Diels−Alder Reaction. Org. Lett. 2005, 7, 5473–
5475.
(21) Chen, W.; Du, W.; Duan, Y.-Z.; Wu, Y.; Yang, S.-Y.; Chen, Y.-C.
Enantioselective 1,3-Dipolar Cycloaddition of Cyclic Enones Catalyzed
by Multifunctional Primary Amines: Beneficial Effects of Hydrogen
Bonding. Angew. Chemie Int. Ed. 2007, 46, 7667–7670.
(22) Lancianesi, S.; Palmieri, A.; Petrini, M. Synthetic Approaches to
3-(2-Nitroalkyl) Indoles and Their Use to Access Tryptamines and
Related Bioactive Compounds. Chem. Rev. 2014, 114, 7108–7149.
(23) McGuirk, C. M.; Stern, C. L.; Mirkin, C. A. Small Molecule
Regulation of Self-Association and Catalytic Activity in a Supramolecular
Coordination Complex. J. Am. Chem. Soc. 2014, 136, 4689–4696.
(24) Dong, X.-W.; Liu, T.; Hu, Y.-Z.; Liu, X.-Y.; Che, C.-M. Urea
Postmodified in a Metal–organic Framework as a Catalytically Active
Hydrogen-Bond-Donating Heterogeneous Catalyst. Chem. Commun.
2013, 49, 7681–7683.
REFERENCES
(1) Cook, T. R.; Zheng, Y.; Stang, P. J. Metal–Organic Frameworks
and Self-Assembled Supramolecular Coordination Complexes:
Comparing and Contrasting the Design, Synthesis, and Functionality of
Metal–Organic Materials. Chem. Rev. 2013, 113, 734–777.
(2) Furukawa, H.; Cordova, K. E.; O’Keeffe, M.; Yaghi, O. M. The
Chemistry and Applications of Metal-Organic Frameworks. Science 2013,
341, 1230444.
(3) Functional Metal-Organic Frameworks: Gas Storage, Separation
and Catalysis; Schröder, M., Ed.; Topics in Current Chemistry; Springer
Berlin Heidelberg: Berlin, Heidelberg, 2010; Vol. 293.
(25) Roberts, J. M.; Fini, B. M.; Sarjeant, A. A.; Farha, O. K.; Hupp, J.
T.; Scheidt, K. A. Urea Metal–Organic Frameworks as Effective and Size-
8
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Page 9 of 10
ACS Catalysis
Selective Hydrogen-Bond Catalysts. J. Am. Chem. Soc. 2012, 134, 3334–
3337.
(26) McGuirk, C. M.; Katz, M. J.; Stern, C. L.; Sarjeant, A. A.; Hupp,
J. T.; Farha, O. K.; Mirkin, C. A. Turning On Catalysis: Incorporation of a
Hydrogen-Bond-Donating Squaramide Moiety into a Zr Metal–Organic
Framework. J. Am. Chem. Soc. 2015, 137, 919–925.
(27) Rueping, M.; Nachtsheim, B. J. A Review of New Developments
in the Friedel–Crafts Alkylation – From Green Chemistry to Asymmetric
Catalysis. Beilstein J. Org. Chem. 2010, 6.
(28) Longmore, R. B.; Robinson, B. The Absolute Configurations of
the Alkaloids of Physostigma Venenosum Seeds. J. Pharm. Pharmacol.
1969, 21, 118S–125S.
(50) Siu, P. W.; Brown, Z. J.; Farha, O. K.; Hupp, J. T.; Scheidt, K. A.
A Mixed Dicarboxylate Strut Approach to Enhancing Catalytic Activity of
a de Novo Urea Derivative of Metal–organic Framework UiO-67. Chem.
Commun. 2013, 49, 10920–10922.
(51) Hamza, A.; Schubert, G.; Soós, T.; Pápai, I. Theoretical Studies on
the Bifunctionality of Chiral Thiourea-Based Organocatalysts: Competing
Routes to C−C Bond Formation. J. Am. Chem. Soc. 2006, 128, 13151–
13160.
(52) Panunto, T. W.; Urbanczyk-Lipkowska, Z.; Johnson, R.; Etter, M.
C. Hydrogen-Bond Formation in Nitroanilines: The First Step in
Designing Acentric Materials. J. Am. Chem. Soc. 1987, 109, 7786–7797.
(53) Wang, J.-J.; Hu, T.-L.; Bu, X.-H. Cadmium(II) and Zinc(II)
Metal–organic Frameworks with Anthracene-Based Dicarboxylic
Ligands: Solvothermal Synthesis, Crystal Structures, and Luminescent
Properties. CrystEngComm 2011, 13, 5152–5161.
1
2
3
4
5
6
7
8
9
(29) Majchrzak, M. W.; Zobel, J. N.; Obradovich, D. J. A Facile
Synthesis of Racemic N α -FMOC-2-Phenyltryptophan. Synth. Commun.
1997, 27, 3201–3211.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(30) Berner, O. M.; Tedeschi, L.; Enders, D. Asymmetric Michael
Additions to Nitroalkenes. European J. Org. Chem. 2002, 2002, 1877–
1894.
(31) Jia, Y.-X.; Zhu, S.-F.; Yang, Y.; Zhou, Q.-L. Asymmetric
Friedel−Crafts Alkylations of Indoles with Nitroalkenes Catalyzed by
Zn(II)−Bisoxazoline Complexes. J. Org. Chem. 2006, 71, 75–80.
(32) Dessole, G.; Herrera, R. P.; Ricci, A. H-Bonding Organocatalysed
Friedel-Crafts Alkylation of Aromatic and Heteroaromatic Systems with
Nitroolefins. Synlett 2004, 13, 2374–2378.
(54) Janiak, C. A Critical Account on π–π Stacking in Metal
Complexes with Aromatic Nitrogen-Containing Ligands. J. Chem. Soc.
Dalton Trans. 2000, 21, 3885–3896.
(55) Blatov, V. A.; Carlucci, L.; Ciani, G.; Proserpio, D. M.
Interpenetrating Metal–organic and Inorganic 3D Networks: A Computer-
Aided Systematic Investigation. Part I. Analysis of the Cambridge
Structural Database. CrystEngComm 2004, 6, 378–395.
(56) Blatov, V. A.; Shevchenko, A. P.; Proserpio, D. M. Applied
Topological Analysis of Crystal Structures with the Program Package
ToposPro. Cryst. Growth Des. 2014, 14, 3576–3586.
(33) Tanaka, K.; Sakuragi, K.; Ozaki, H.; Takada, Y. Highly
Enantioselective Friedel–Crafts Alkylation of N , N -Dialkylanilines with
Trans -β-Nitrostyrene Catalyzed by
a Homochiral Metal–organic
Framework. Chem. Commun. 2018, 54, 6328–6331.
(34) Kim, H. Y.; Kim, S.; Oh, K. Orthogonal Enantioselectivity
Approaches Using Homogeneous and Heterogeneous Catalyst Systems:
Friedel-Crafts Alkylation of Indole. Angew. Chemie Int. Ed. 2010, 49 ,
4476–4478.
(35) Ganesh, M.; Seidel, D. Catalytic Enantioselective Additions of
Indoles to Nitroalkenes. J. Am. Chem. Soc. 2008, 130, 16464–16465.
(36) Singh, P. K.; Bisai, A.; Singh, V. K. Enantioselective Friedel–
Crafts Alkylation of Indoles with Nitroalkenes Catalyzed by
a
Bis(Oxazoline)–Cu(II) Complex. Tetrahedron Lett. 2007, 48, 1127–1129.
(37) Herrera, R. P.; Sgarzani, V.; Bernardi, L.; Ricci, A. Catalytic
Enantioselective Friedel-Crafts Alkylation of Indoles with Nitroalkenes by
Using a Simple Thiourea Organocatalyst. Angew. Chemie Int. Ed. 2005,
44, 6576.
(38) Schreiner, P. R. Metal-Free Organocatalysis through Explicit
Hydrogen Bonding Interactions. Chem. Soc. Rev. 2003, 32, 289–296.
(39) Ian Storer, R.; Aciro, C.; Jones, L. H. Squaramides: Physical
Properties, Synthesis and Applications. Chem. Soc. Rev. 2011, 40, 2330.
(40) Schreiner, P. R.; Wittkopp, A. H-Bonding Additives Act Like
Lewis Acid Catalysts. Org. Lett. 2002, 4, 217–220.
(41) Takemoto, Y. Recognition and Activation by Ureas and
Thioureas: Stereoselective Reactions Using Ureas and Thioureas as
Hydrogen-Bonding Donors. Org. Biomol. Chem. 2005, 3, 4299–4306.
(42) Doyle, A. G.; Jacobsen, E. N. Small-Molecule H-Bond Donors in
Asymmetric Catalysis. Chem. Rev. 2007, 107, 5713–5743.
(43) Fleming, E. M.; McCabe, T.; Connon, S. J. Novel Axially Chiral
Bis-Arylthiourea-Based Organocatalysts for Asymmetric Friedel–Crafts
Type Reactions. Tetrahedron Lett. 2006, 47, 7037–7042.
(44) Wan, N.; Hui, Y.; Xie, Z.; Wang, J. Friedel-Crafts Alkylation of
Indoles with Nitroalkenes Catalyzed by Zn(II)-Thiourea Complex.
Chinese J. Chem. 2012, 30, 311–315.
(45) Zhu, C.; Mao, Q.; Li, D.; Li, C.; Zhou, Y.; Wu, X.; Luo, Y.; Li, Y.
A Readily Available Urea Based MOF That Act as a Highly Active
Heterogeneous Catalyst for Friedel-Crafts Reaction of Indoles and
Nitrostryenes. Catal. Commun. 2018, 104, 123–127.
(46) Rao, P. C.; Mandal, S. Friedel-Crafts Alkylation of Indoles with
Nitroalkenes
through
Hydrogen-Bond-Donating
Metal-Organic
Framework. ChemCatChem 2017, 9 , 1172–1176.
(47) Zhang, X.; Zhang, Z.; Boissonnault, J.; Cohen, S. M. Design and
Synthesis of Squaramide-Based MOFs as Efficient MOF-Supported
Hydrogen-Bonding Organocatalysts. Chem. Commun. 2016, 52, 8585–
8588.
(48) Hall, E. A.; Redfern, L. R.; Wang, M. H.; Scheidt, K. A. Lewis
Acid Activation of a Hydrogen Bond Donor Metal–Organic Framework
for Catalysis. ACS Catal. 2016, 6, 3248–3252.
(49) Alegre-Requena, J. V; Marques-Lopez, E.; Herrera, R. P.; Diaz, D.
D. Metal-Organic Frameworks (MOFs) Bring New Life to Hydrogen-
Bonding Organocatalysts in Confined Spaces. CrystEngComm 2016, 18,
3985–3995.
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