MIL-101-SO3H metal-organic framework as a Br?nsted acid catalyst in Hantzsch reaction: An efficient and sustainable methodology for one-pot synthesis of 1,4-dihydropyridine

Article abstract of DOI:10.1039/c9nj00990f

A straightforward and efficient methodology for the one-pot multicomponent synthesis of 1,4-dihydropyridine has been developed using MIL-101-SO₃H metal-organic framework as a solid Br?nsted acid. The presence of the uniformly distributed Br?nsted acidic sulfonic acid sites throughout the framework and the high stability bestow the catalyst with excellent reactivity towards the synthesis of 1,4-dihydropyridine under simple reaction conditions using renewable ethanol as the solvent. The present methodology tolerates various functional groups and allows the synthesis of 1,4-dihydropyridine derivatives in good to excellent yields through Hantzsch reaction. The developed methodology proceeds under mild conditions, avoids corrosive reagents and special reaction conditions, and is amenable to gram scale synthesis. The sustainable nature of the catalyst was proved by the easy recovery and the reusability of the catalyst, as it was reused several times without loss in activity, which was confirmed from the FTIR, PXRD and SEM analyses of the reused catalyst.

Full text of DOI:10.1039/c9nj00990f

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Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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MIL-101-SO3H Metal-Organic Framework as a Brønsted Acid
Catalyst in Hantzsch Reaction: An Efficient and Sustainable
Methodology for One-Pot Synthesis of 1,4-Dihydropyridine
Received 00th January 20xx,
Accepted 00th January 20xx
Nainamalai Devarajan and Palaniswamy Suresh*
DOI: 10.1039/x0xx00000x
www.rsc.org/
A straightforward and efficient methodology for the one-pot multicomponent synthesis of 1,4-dihydropyridine has been
developed using MIL-101-SO3H Metal-Organic Framework as a solid Brønsted acid. The presence of the uniformly
distributed Brønsted acidic sulfonic acid sites throughout the framework and high stability bestow excellent reactivity of
the catalyst towards the synthesis of 1,4-dihydropyridine under simple reaction conditions using renewable ethanol as a
solvent. The present methodology tolerates various functional groups and allows the synthesis of 1,4-dihydropyridine
derivatives in good to excellent yield through Hantzsch reaction. The developed methodology proceeds under a mild
condition, avoid corrosive reagents and special reaction conditions, also amenable to gram scale synthesis. Sustainable
nature of the catalyst was proved by the easy recovery and reused for several times without loss in activity and which was
confirmed from the FTIR, PXRD and SEM analyses of the reused catalyst.
construction of heterocyclic motifs with the reusable
heterogenous catalytic system has recently been emerged as a
thrust area.5 Notably, the development of non-corrosive,
environmentally friendly and multi-reusable acid catalyst is a
contemporary requirement for the pharma industry for the
synthesis of drugs and fine chemicals owing to their need for
more environment concern. Efforts have been made for the
development of strongly acidic, readily separable and
recyclable solid Brønsted acid catalyst to carry out hassle-free
organic transformations.
Introduction
1,4-dihydropyridines (1,4-DHPs) are pivotal and privileged class
of heterocyclic compound which has many significant
biological and pharmacological activities.1 More than twelve
medicinally important 1,4-DHPs based drugs are available in
the market.2 Fig. 1.
Metal–Organic Frameworks (MOFs) are organic-inorganic
hybrid materials that have gained broad scope in
heterogeneous catalysis owing to the presence of large surface
Fig. 1 Drugs containing 1,4-DHP moieties.
area,
extra-high
porosity,
and
tunable
chemical
functionalities.6 MOFs are well known for their Lewis7 and
Brønsted acidity8/basicity9 which originates from the
coordinatively unsaturated metal sites and functional groups
present on the organic linkers respectively. Recently the
application of sulfonic acid functionalized catalyst exotically
employed in organic synthesis for selective construction of
organic motifs and identified as a potential alternate to the
conventional acid catalyst. Brønsted acidity arose from the
active sites suspended on the organic linkers of MOF which
shows exceptional activity and versatile solid acidic catalytic
performance in the synthetic transformations.8 Among, the
pre-sulfonic acid functionalized MIL-101-SO3H MOF possess
highly dense and uniform acidic sites, exhibits high activity
with good stability than the post-synthetically functionalized
acidic MOFs.10 The Lewis acidity of the MIL-101-SO3H is
relatively negligible, and Brønsted acidic sulfonic acidic sites
are more pronounced and used as a solid acid catalyst for
Most of the 1,4-DHPs were achieved through multicomponent
strategy using homogeneous3 and heterogeneous4 catalysts.
However, reported catalysts and methodologies has
associated with inherent demerits like tedious catalyst
preparation, toxic nature, harsher conditions, longer reaction
time, unwanted by-products, inferior in yields, and difficulties
in recovery and reusability of the catalysts. Though
multicomponent reactions have developed as an efficient and
powerful tool in modern synthetic organic chemistry, the
Supramolecular and Catalysis Lab, Dept. of Natural Products Chemistry,
School of Chemistry, Madurai Kamaraj University, Madurai-625021, India.
E-mail: ghemistry@gmail.com, suresh.chem@mkuniversity.org
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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various organic transformations such as esterification,10b,11 polar solvents toluene and 1,2-dichloroethane leVaidewtAorticalegOonolinde
deacetalization–nitroaldol reaction,12 alcoholysis of epoxides13 yield, meanwhile mid-polar solvents sucDhOaI:s10T.H10F3,9c/Ch9loNrJo0f0o9r9m0F,
and acetalization.14 In the synthesis of bioactive heterocycles, and 1,4-dioxane gave moderate yield. In the case of high polar
the potential of MOF has scantly been investigated as a Lewis protic and aprotic solvents such as methanol, ethanol, IPA, n-
acid catalyst,15 albeit, not gained much attention due to their butanol, ACN, DMF, DMSO and ethylene glycol promotes
poor chemical stability of the framework metals. Though, post- reaction with comparable yield than the other solvents. In
synthetically functionalized sulfonic acid containing MOFs order to improve the greener context of the synthesis,
employed in the heterocycles synthesis,16 however, owing to reactions were performed using ethanol-water mixture and as
the complex preparation methods and poor stability impetus well under the neat conditions, but the results were not
to identify a robust and acidic MOFs as catalyst.16b Therefore, impressive and gave moderate yield (entries 9, 10 and 16,
in the present work, using pre-sulfonic acid functionated MIL- Table 1). Based on the reaction progress and with green
101-SO3H MOF has been employed as a solid Brønsted acid chemistry recommendations,17 readily available renewable
catalyst for the synthesis of 1,4-DHPs through Hantzsch solvent, ethanol was chosen as the reaction medium. Further
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reactions under benign reaction condition.
aqueous ammonia was used as an alternate nitrogen source
instead of ammonium acetate to avoid the formation of acetic
acid during the course of the reaction; however, the yield was
decreased (entry 8, Table 1). Though the reaction temperature
was fixed arbitrarily at 60 °C to choose suitable solvent,
additional reactions were performed at different temperatures
ranges (entry 8, Table 1) which reveal that the change in
temperature directly influences the product formation.
Decrease in temperature resulted with inferior yield and
raising the temperature did not promote the yield. Also, the
reaction was carried out at room temperature and 50 °C,
resulted 90%, and 93% of yield, respectively. However,
removal of the unreacted precursors and purification
consumes more time and solvent. While raising the
temperature to 75 °C, there was no notable change in the yield
(entry 8, Table 1). All reactants were converted into product
without any by-product at 60 °C, which was fixed as optimum
temperature.
Results and discussion
To optimize a mild and straightforward methodology for the
synthesis of 1,4-DHPs using MIL-101-SO3H-MOF (1) as a solid
Brønsted acid catalyst, a model reaction was performed using
benzaldehyde (2a), ethyl acetoacetate (3a) and ammonium
acetate (4) as the model substrates to screen various catalytic
parameters such as solvent, time, catalyst and its load, at the
arbitrarily fixed temperature 60 °C. The observed results from
the screening studies were listed in table 1. A spectrum of
solvents from non-polar to polar were tested to choose a
reliable solvent for 1 MOF catalyzed synthesis of 1,4-DHP. Non-
Table 1 Effect of solvent on the Hantzsch Reactiona
In continuation with solvent and temperature optimization,
the effect of time was studied. Initially, the reaction was
allowed to proceed for 12 h, and the progress of the reaction
was periodically monitored for every 2 h. All starting materials
were consumed after 8 h with a high yield of 99% (Fig. 2). It
defines that the reaction is highly time-dependent, and
shorten the reaction time which directly influences the yield
with moderate conversions.
Entry
1
2
3
4
5
6
7
8
Solvent
Toluene
1,2-Dichloroethane
THF
Chloroform
1,4-Dioxane
Acetonitrile
Methanol
Ethanol
Yieldb (%)
76
71
50
67
59
75
90
90c, 93d, 99, 99e, 82f
9
Ethanol/water (9:1)
Ethanol/water (1:1)
IPA
n-Butanol
DMF
DMSO
Ethylene Glycol
Solvent-free
76
60
72
78
74
71
68
60
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11
12
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16
a
Reaction conditions: MIL-101-SO3H MOF (20 wt%),
benzaldehyde (0.94 mmol, 1.0 eq), Ethyl acetoacetate (1.88
mmol, 2.0 eq), and ammonium acetate (0.94 mmol, 1.0 eq)
was carried out in solvent (1.0 mL) at 60 °C for 12 h under air.
b Isolated yield, c rt, d 50 °C, e 75 °C, f aq. NH3.
Fig. 2 Time optimization for MIL-101-SO3H catalyzed
Hantzsch Reactions.
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In heterogeneous catalysis, the amount of catalyst would
determine the efficiency as well as endorse the greener nature
of the catalyst. In the present study, increase in the catalyst
loading from 5 wt% to 30 wt% exhibited a remarkable
enhancement in the yield and shown that 20 wt% catalysts
was sufficient to attain the maximum yield (99%). Other by-
products or impurities not found under the optimized
conditions, and the reaction was almost faint in the absence of
the catalyst (Fig. 3).
View Article Online
Table 2 MIL-101-(SO3H) MOF catalyzed HaDnOtzIs:c1h0.R10e3a9c/tCio9nNaJ00990F
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Fig. 3 Optimization of catalyst load on the Hantzsch
Reactions.
With the screened parameters such as ethanol as a solvent,
20 wt% of 1 MOF as catalyst at 60 °C in an open vessel, to
explore the universality of the catalyst, structurally and
electronically diverse aldehydes were selected and reacted
with ethyl acetoacetate and ammonium acetate. Aryl
aldehydes possessing either electron-donating or electron-
withdrawing substituents were smoothly undergoing Hantzsch
reaction yielded the corresponding 1,4-DHPs (5a-5af) with 68%
to 99%. The electronic effect of the substituents presents on
the aldehydes not much influenced in the formation of 1,4-
DHPs, it clearly understands from the observed results. The
aryl aldehydes possessing electron-donating substituents such
as methyl, methoxy, ethoxy, hydroxy groups (5b-5h, Table 2)
afforded the corresponding 1,4-DHPs in good to excellent yield.
Aldehydes with electron-withdrawing groups such as halogens,
carboxylic acid, nitro, and nitrile also gave a good yield.
Aldehydes with halides (5i-5m, Table 2) resulted in good yields
from 89-99% except with 2,3,4-trifluorobenzaldehyde which
forms only 80% of product (5j) owing to the steric hindrance.
Meanwhile, presence of carboxylic acid (5o, Table 2), boronic
acid (5p, Table 2), nitro (5q-5s, Table 2), and nitrile (5t and 5u,
Table 2), groups gave better yields 85-96%. Among the
chemically liable groups such as boronic acid and nitrile were
stable without any further oxidation. Added to that, the chloro,
bromo, nitro, boronic acid and nitrile groups are synthetically
useful since these products can be easily further functionalized.
The presence of both methoxy and chloro substituents on an
aldehyde also proceeds smoothly with a good yield (5n, Table
2) 89%. A mild drop in the reactivity was observed when
heterocyclic aldehydes with free nitrogen moiety and gave a
moderate yield (5v-5w, Table 2) 68-75%. It may due to the
adsorption of the free base group with catalyst’s sulfonic acid
a
Reaction conditions: MIL-101-SO3H MOF (1) (20 wt%),
aldehydes (1.0 eq), 1,3-dicarbonyl compound (2.0 eq),
and ammonium acetate (1.0 eq) was carried out in EtOH
(1.0 mL) at 60 °C for 8 h in an open vessel. All are isolated
yields.
group and affects the product conversion. Conversely, N-
methylated aldehyde and oxygen-containing heterocyclic
aldehydes (5x-5z, Table 2) gave excellent yield without any
interfere. Unsaturated aldehyde (5aa, Table 2) provided 98%
yield, and aliphatic aldehydes (5ab-5ad, Table 2) gave the
corresponding 1,4-DHPs in good yield 83-91%. Finally, other
active methylene compounds like methyl acetoacetate and
acetylacetone were also tested and offered the excellent yield
of 1,4-DHPs (5ae-5af). The potential of the catalyst MIL-101-
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SO3H (1) has also been tested for bulk scale production of 1,4- overnight. Then the pyridine adsorbed catalystVwiewaAsrtifcilletOenrelinde
DHPs using 1 g of benzaldehyde with ethyl acetoacetate and and dried at 110 °C under high vacuum in a glass oven for 12 h.
ammonium acetate and yields (99%) as in minimum batch The pyridine adsorbed catalyst catalyzed reaction gave the
DOI: 10.1039/C9NJ00990F
reaction condition.
poor conversion of 15% (entry 7, Table 3). From the observed
6
Though, the sulfonic acid functional moiety presents on the results, the role of the open -SO3H group has unambiguously
1 MOF catalyzed the Hantzsch reaction under the optimized disclosed and revealed that the presence of a high surface area,
reaction condition, in order to ascertain the potential of the porous nature, and the open Brønsted acidic (SO3H) catalytic
sulfonic acid group present in the framework, other similar center on organic linker cooperatively plays a vital role for
type of catalysts were tested in the synthesis of 1,4-DHPs Hantzsch 1,4-DHPs synthesis.
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under the identical optimized conditions. The precursors of the
1
MOF,
CrO3,
Cr(NO3)2.9H2O,
monosodium-2-
Heterogeneity Test
sulfoterephthalate and terephthalic acid were used as a
catalyst. Using stoichiometric quantity of the above-noted
reagents gave moderate yield (entries 1-4, Table 3). Further,
the corresponding metal node and the organic linker of the 1
MOF, CrO3 and monosodium-2-sulfoterephthalate were
employed as a 1:1 physical mixture in the Hantzsch reaction,
which resulted with the moderate yield (66%; entry 5, Table 3).
However, the product separation and purification are arduous,
and the use of a stoichiometric amount of catalyst is an
inherent limitation of the homogeneous catalytic system. The
above control experiments demonstrate the advantages of
sulfonic acid group present on the framework of 1 in the
Hantzsch 1,4-DHPs synthesis.
Furthermore, the reaction was inferior with the native MIL-
101 (entry 6, Table 3) even under nitrogen atmosphere, which
reveals that, when Cr3+ is not reactive within in the framework
in ethanol medium as like free slats owing to small pore size
and difficulty to access the metal sites.13 This observation
unleashes the importance of the -SO3H in present reaction.
Furthermore, pyridine adsorption study was carried out to
ascertain the role of -SO3H. The catalytically responsive open
Brønsted acid sites in 1,4-DHPs synthesis were hampered
externally by soaking the catalyst in excess of pyridine for
In 1 MOF, the catalytic activity has originated from the sulfonic
acid functionality present on the organic linker. However,
there is a possibility of Lewis acidic Cr3+ may promote the 1,4-
DHP synthesis, if it leached from the secondary building unit of
1 MOF, since a remarkable reactivity of chromium(III) ions has
noted in the present study (entries 1, 2, Table 3). To verify the
true heterogeneity of the catalyst 1, a hot filtration test was
performed. The reaction proceeded smoothly with 67% yield
in 2 h. After, the catalyst was removed from the reaction
mixture by simple centrifuge and the mother liquor was
further allowed to stir for the optimized reaction time and
aliquots were analyzed in gas chromatography for every 2 h
intervals (Fig. 4). From the hot filtration test result, a slight
increase (72%) in the product conversion was noted, owing to
acetic acid generated during the course of the reaction.
However, no further improvement in the product conversion
was noted even after 10 h in the absence of the catalyst under
optimized conditions. It confirms that there was no leaching of
Cr3+, and the reaction could not proceed in the absence of MIL-
101-SO3H. Hot filtration test strongly dictates that the 1 MOF
was highly stable and retains its true heterogeneity under the
present reaction condition without any structural deformation
or decomposition. The observed results are strongly supported
by the inductively coupled plasma optical emission
spectroscopy (ICP-OES) measurement of the filtrate from the
reaction mixture in which no evidence for Cr3+ leaching and
dictate that 1 MOF is truly heterogeneous.
Table 3 Effect of various catalysts on the Hantzsch Reactionsa
Entry Catalyst
Yieldb (%)
60c
1
2
3
4
5
CrO3
Cr(NO3)2.9H2O
Monosodium-2-sulfoterephthalate
Terephthalic acid
CrO3:monosodium-2-
sulfoterephthalate
MIL-101
62c
43c
55c
66d
6
7
4e, 18f
15e
99e
Pyridine adsorbed MIL-101-SO3H
MIL-101-SO3H
8
a
Reaction conditions: Benzaldehyde (0.94 mmol, 1.0 eq),
Fig. 4 Hot filtration test for the true heterogeneity
of 1.
Ethyl acetoacetate (1.88 mmol, 2.0 eq), and ammonium
acetate (0.94 mmol, 1.0 eq) was carried out in EtOH (1.0
mL) at 60 °C for 8 h under air. b Isolated yield, c 1.0 eq, d as
a 1:1 physical mixture, e 20 wt%, f under nitrogen atm.
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Furthermore, to explain the sustainable nature of the catalyst, course of the reaction and even after eight-time reused.
View Article Online
after reaction completed, MOF catalyst was separated from However a traces of 1,4-DHPs adsorbeDdOoI:n10.t1h0e39/fCra9mNJe0w09o9r0kF,
ethanol followed by an excess of DMF, and then activated at which understand from the new peaks appeared 1080 and
110 °C for 2 h in a glass oven. New reactions were conducted 1180 cm-1.
with the recovered catalyst, and it exhibited good catalytic
Likewise, the powder XRD patterns (Fig. 7) of recovered
activity up to eight consecutive cycles (Fig. 5). However, there MOF catalyst were closely matched with the fresh catalyst and
was a minimum drop in the activity of the catalyst was noted retained its crystallinity. It reveals that the polymeric network
after the fifth cycle owing to repeated usage of the catalyst.
of the framework does not undergo any deformation or
collapse even after eight consecutive recycles. The PXRD result
supported by the SEM analysis of the reused catalyst and (Fig.
8) the surface morphology of the recovered catalyst not
showed any strong erosion, and the original morphology of 1
MOF was retained even after eight-time reused.
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Fig. 5 Reusability profile of MIL-101-SO3H MOF in
Hantzsch Reactions.
The reusability results show that the catalyst is highly stable up
to eight consecutive cycles without any significant loss in its
catalytic activity. Meantime, to ascertain the fate of the reused
catalyst at each cycle, it was subjected to FTIR, PXRD and SEM
analyses.
The FTIR analysis of the reused catalysts show that the
vibrational bands are almost identical with the as-synthesized
MOF catalyst without any new peaks, even after eight times
reused. The vibration bands appeared at 1160 and 1292 cm-1
show that there is no detachment of sulfonic acid group from
the organic linker of the framework and the absence of strong
absorption bands at 1760–1690 cm-1 (Fig. 6) unveils that the
framework does not undergo any decomposition during the
Fig. 7 Powder XRD patterns fresh and reused used MIL-
101-SO3H MOF. a) fresh, b) first, c) fifth and d) eighth
run.
Fig. 8 SEM images of fresh and reused used MIL-101-
SO3H MOF. a) fresh, after b) fifth and c) eighth run.
The uniqueness of the catalyst 1 is rationalized based on its
selectivity in 1,4-DHPs synthesis over the other existing system
which is spectacle by comparison with the other reported
homogeneous and heterogeneous catalyst (Table 4). Present
sulfonic acid functionalized MIL-101 MOF exhibits a better
catalytic activity in Hantzsch reaction in terms of catalyst load,
reaction time, temperature and selectivity. In analogy, MIL-
101-SO3H is highly stable, resuable, and scalble catalyst for the
synthesis of 1,4-DHPs.
In accordance with previous studies7a,7l,18 and with our
results, a plausible mechanism has outlined in scheme 1 for
the 1 MOF catalyzed the synthesis of 1,4-DHPs. Initially, the
Brønsted acidic sulfonic acid group present in the 1 activates
Fig. 6 FTIR spectra of fresh and reused used MIL-101-
SO3H MOF. a) fresh, b) first, c) fifth and d) eighth run.
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In the present work, it is demonstrated that MIL-101-SO3H
MOF (1) can be used as a straightforward and sustainable
View Article Online
DOI: 10.1039/C9NJ00990F
catalyst for the synthesis of a pharmaceutically essential 1,4-
dihydropyridines through one-pot multicomponent reaction
strategy with good to excellent yield. The MIL-101-SO3H MOF
catalyzes the Hantzsch reaction under mild reaction condition
using readily available and renewable ethanol as a greener
solvent with good functional group tolerance and broader
substrate scope. A simple and efficient protocol has been
developed to get a series of 1,4-dihydropyridines using the as-
prepared MIL-101-SO3H MOF as catalyst. The MIL-101-SO3H
MOF showed high stability and reactivity than the post-
synthetically tuned sulfonic acid MOF catalyst. The stability of
the catalyst is proved by hot filtration test and reused for eight
times with a slight decay in the catalytic behavior. The high
stability and reactive nature of the Brønsted acidic MOF
catalyst expands the scope for its broad application in
medicinal chemistry.
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Experimental
General Information
All reagents, starting materials and solvents were purchased
commercially from Sigma-Aldrich, Alfa-Aesar, Merck, TCI,
Himedia or CDH and were used as received without any
further purification unless otherwise noted. All 1H and 13C
NMR spectra were measured either in CDCl3 or DMSO-d6 with
Scheme 1. A plausible mechanism for the formation of
1,4-DHPs catalyzed by MIL-101-SO3H MOF.
Table 4 Comparison of catalytic potential of MIL-101-SO3H MOF in the synthesis of 1,4-Dihydropyridine
S. No.
Catalyst
p-TSA
PPh3
Chlorosulphonic acid
In/SiO2
Silica Sulfuric Acid
Alginic acid
Lignosulfonic Acid
SiO2–SO3H
Solvent
SDS (aq)
EtOH
-
Catalyst load
10 mol %
20 mol %
20 %
10 mol %
0.26 mmol
10 mol %
3.8 mol %
0.2 g
Temp (°C)
rt., (ultrasound)
reflux
rt., (grinding)
reflux
rt.,
reflux
90
Time (h)
1
5
20 min.,
5
20 min.,
1
2
5.5
1
Yield (%) Reusability
Ref.
3b
3d
20
21
4h
4l
4m
18a
22
1
2
3
4
5
6
7
8
9
10
96
72
84
88
96
97
90
90
98
86
-
-
-
-
5
6
4
8
5
6
IPA
Neat
EtOH
Neat
Neat
Neat
EtOH
60
90
γ-Fe2O3-SO3H
SBA-SO3H
0.025 g
10 mol %
rt., (Sonicated)
25 min.,
23
This
work
11
MIL-101-SO3H
EtOH
20 wt%
60
8
99
8
the carbonyl group of β-ketoester (3) which undergoes TMS as an internal standard by using a 300 MHz on a Bruker
Knoevenagel condensation with aldehyde (2) give the spectrometer. ESI-MS was performed by using an LCQ Fleet,
intermediate I and parallelly another equivalent of β-ketoester Thermo-Fisher Instruments Limited, US. The collision voltage
(3) reacts with ammonium acetate and generates enamine and ionization voltage were –70 V and –4.5 kV, respectively,
intermediate II, with water and acetic acid as by-products. and N2 was used as the atomization and desolvation gas. The
Further intermediates I and II undergo intermolecular Michael desolvation temperature was set at 300 °C. The powder XRD
addition results the III. Then III undergo tautomerization patterns of the MOF were recorded by using an XPERT-PRO
results in IV which is activated by the Brønsted acidity of the instrument using CuKα radiation at RT. FTIR spectra of the
catalyst 1 and undergo intramolecular cycloaddition with imine MOF were recorded by using a Shimadzu instrument from
and subsequent dehydration of third water molecule affords 4500 to 450 cm-1, and the samples were dispersed using the
the corresponding 1,4-DHPs compounds (5).
KBr pellet technique. Brunauer Emmett Teller (BET) surface
area analysis was carried out using the Quantachrome-
Autosorb at 77 K. A Netzsch Thermoanalyzer STA 409 was used
for thermogravimetric analysis (TGA) with a heating rate of
Conclusions
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10 °C min-1 under a N2 atmosphere at 50–800 °C. GC was peaks from 2θ (2° to 8°) indicates that the MOVFiewwAarsticlhe iOgnhlinlye
performed by using a Shimadzu instrument with a flame crystalline in nature, and the observed pattern exactly matches
ionization detector (FID) and a ZB-5 column (length = 30 m, reported patterns.
DOI: 10.1039/C9NJ00990F
inner diameter = 0.25 mm, and film thickness = 0.25 mm) using
The thermal stability is another necessary characteristic
a temperature program from 100 to 250 °C at 10 °C min-1. SEM feature of the MOF to act as a potential catalyst. As shown in
was performed by using a TESCAN VEGA3 instrument using a (Fig. S3) the TGA pattern, the first weight loss at 85-120 °C is
SE detector and equipped with an EDAX energy-dispersive X- due release of absorbed methanol and water molecules in the
ray spectroscopy (EDX) detector. ICP-OES was performed by pores of the MOF. Then the second weight loss takes place
10
11
12
13
14
15
16
17
18
19
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22
23
24
25
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35
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using a PerkinElmer OPTIMA 5300 DV.
between 250-350 °C due to the thermal decomposition of
sulfonic acid moiety. The final weight loss at 500 °C shows the
complete collapse of the framework which is almost matches
with previous reports. The nitrogen physisorption
measurements revealed the presence of a porous structure in
MIL-101-SO3H. From the BET method, the surface area was
measured as 1497 m2g−1. EDAX analysis (Fig. S4) shows the
presence 13.47 wt% of Chromium and 3.42% of sulfur in MIL-
101-SO3H. These above characterization results and the
powder XRD pattern were in good agreement with literature.
The SEM image shows that MIL-101-SO3H particles get
aggregated.
Synthesis and Characterization of MIL-101-SO3H (1)
MIL-101-SO3H MOF was synthesized by
a hydrothermal
process as reported.19,13
A
mixture of monosodium 2-
sulfoterephthalic acid (2.68 g, 99.94 mmol), CrO3 (1.0 g, 10
mmol), in concentrated aqueous hydrochloric acid (0.53 mL)
was dissolved in water (20 mL) and then transferred into a
Teflon-lined stainless-steel autoclave. Next, it was placed in an
air oven at 180 °C for 168 h under the hydrothermal conditions.
After, the autoclave was naturally cooled to room temperature
and opened. The resulting product was filtered and washed
with excess of deionized water (400 mL) followed by methanol
(100 mL), then the resulting product was dried in air at room
temperature. The green powder was immersed in DMF and
heated at 120 °C for 24 h followed by addition of mixer of
methanol and water and again maintained at 120 °C for 24 h.
The resulting microcrystalline green powder (MIL-101-
SO3Na(H)) was further treated with diluted HCl (0.08 M) in
methanol and water solution and was further treated with
methanol followed by water to remove excess of HCl. The
resultant green solid was finally dried overnight at 120 °C
under vacuum prior to use. The product was characterized by
FTIR spectroscopy, powder XRD, SEM, EDX, and TGA.
In FTIR analysis (Fig. S1) of MIL-101-SO3H shows the
absence of strong absorption band at 1760–1690 cm-1 and the
presence of strong peak at 1610 cm-1, which was lower than
the C=O stretching vibrations of free carboxylic acids were
confirmed the deprotonation of carboxylic acid groups7b,7c in
monosodium 2-sulfoterephthalic acid. The peak at 579 cm-1 is
ascribed to Cr–O stretching vibration.24 The peaks appeared at
1160 and 1292 cm-1 along with a shoulder peak at 1435 cm-1
are the characteristic peaks for O=S=O group’s symmetric and
asymmetric stretching mode of vibration.10a,25 Similarly, the
band appears at 1020 cm-1 corresponds to the S–O stretching
vibration.10b,16b The peak at 1104 cm-1 refers to the in-plane
skeletal vibration of the SO3 group substituted on the aromatic
rings of terephthalate organic linker.10b The wide peak appears
at 3405 cm-1 is the characteristic peak for –OH group present
in the –SO3H.16b The presence of dicarboxylate groups (-O-C-O)
in the framework is confirmed by the peak at 1400 cm-1.16a
Finally, the peak at 747 cm-1 and a shoulder peak at 635 cm-1
represent C-S stretching vibration.11 The other peaks
correspond to sulfonic acid groups are also appeared in the
region of 600 to 1400 cm-1, although these peaks shift to some
extent in comparison with that PSM method, probably due to
a higher density of the preinstalled SO3H group.10b In the
powder XRD pattern (Fig. S2), the presence of a very sharp
General Procedure for the Synthesis of 1,4-DHP using MIL-101-
SO3H MOF as a Catalyst Reaction
A mixture of aldehyde (2) (1.0 eq), 1,3-dicarbonyl compound (3)
(2.0 eq), and NH4OAc (4) (1.0 eq) were mixed together and
dissolved in 1.0 mL of ethanol in an oven dried reaction tube
fitted with condenser and placed in an oil bath at 60 °C. Then
20 wt% of MIL-101-SO3H MOF (1) catalyst was added to the
reaction mixture and continued for up to 8 h in an open vessel.
After the reaction was completed, cooled to room
temperature and the catalyst was separated by simple
centrifuge, further the catalyst was repeatedly washed with
ethanol to remove the products from the MOF pores. The
combined mother liquor was evaporated to dryness under
vacuum and the crude product was diluted with ethyl acetate
and washed with water and brine solution. The organic phase
was collected, dried with sodium sulfate and concentrated to
dryness. The obtained crude was triturated with diethyl ether
to get pure product which was analyzed by using NMR
spectroscopy and ESI-MS. After the extraction of the product,
MIL-101-SO3H MOF was washed with ethanol followed by DMF
and then immersed in DMF and heated at 100 °C for 1 h.
Finally after solvent removed by filtration dried at 120 °C for 3
h under vacuum to the further reuse.
Conflicts of interest
There are no conflicts to declare.
Acknowledgments
We gratefully acknowledge the financial support from the
Science and Engineering Research Board SERB), New Delhi,
India under fast-track scheme (Grant No. SR/FT/CS-53/2011).
Also, we acknowledge University Grants Commission, New
This journal is © The Royal Society of Chemistry 20xx
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A. Dꢀmling, W. Wang and K. Wang, Chem. Rev., 2012, 112,
Delhi, India (UGC grant No.: 42-291/2013(SR)) and Council for
Scientific and Industrial Research, New Delhi, India (CSIR grant
No.: 02(0191)14/EMR-II). We thank University Grants
Commission under University with Potential for Excellence
program (UGC-UPE), DST-FIST (for LC-MS) and DST-PURSE (for
FTIR, SEM, and EDX) for the instrumental facility.
View Article Online
3083.
(a) J. Liu, L. Chen, H. Cui, J. Zhang, LD. OZIh: a10n.g103a9n/dC9CN.J0-Y0.99S0uF,
Chem. Soc. Rev., 2014, 43, 6011; (b) A. H. Chughtai, N.
Ahmad, H. A. Younus, A. Laypkov and F. Verpoort, Chem. Soc.
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2953; (b) N. Devarajan, M. Karthik and P. Suresh, Org.Biomol.
Chem., 2017, 15, 9191; (c) N. Devarajan and P. Suresh, Org.
Chem. Front., 2018, 5, 2322; (d) Y. -S. Kang, Y. Lu, K. Chen, Y.
Zhao, P. Wang and W. -Y. Sun, Coord. Chem. Rev., 2018, DOI:
10.1016/j.ccr.2018.02.009.
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Table of Content
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MIL-101-SO3H Metal-Organic Framework as a Brønsted Acid Catalyst
in Hantzsch Reaction: An Efficient and Sustainable Methodology for
One-Pot Synthesis of 1,4-Dihydropyridine
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Nainamalai Devarajan, Palaniswamy Suresh*
A straightforward and efficient methodology for the synthesis of medicinally
important 1,4-dihydropyridines has been demonstrated using MIL-101-SO3H Metal-
Organic Framework as a sustainable Brønsted acid catalyst.