A Primary Amide-Functionalized Heterogeneous Catalyst for the Synthesis of Coumarin-3-carboxylic Acids via a Tandem Reaction

Article abstract of DOI:10.1021/acs.inorgchem.0c01178

A crystalline primary amide-based bifunctional heterogeneous catalyst, {[Cd2(2-BPXG)(Fum)2(H2O)2]·2H2O}n (1) (where, 2-BPXG = 2,2′-((1,4-phenylenebis(methylene))bis((pyridin-2-ylmethyl)azanediyl)) diacetamide and Fum = fumarate), has been developed for the one-pot synthesis of a series of potentially biologically active coumarin-3-carboxylic acids at room temperature via a Knoevenagel-intramolecular cyclization tandem reaction. Catalyst 1 is prepared at room temperature from a one-pot self-assembly process in 81% yield and high purity within a few hours and has a ladder-like polymeric architecture based on single-crystal X-ray diffraction. Additional characterization of 1 includes elemental analysis, infrared spectroscopy, thermogravimetric analysis, and powder X-ray diffraction. Based on the optimized conditions, it is determined that 1 is highly efficient (conditions: 2 mol % catalyst, 3 h, and 26-28 °C in methanol) for this reaction. Its recyclability up to five cycles without significant loss of activity and structural integrity is also demonstrated. Using both electron-donating and electron-withdrawing substituents on the salicylaldehyde substrate, seven different derivatives of coumarin-3-carboxylic acid were made. Additionally, the monoamine oxidase (MAO) inhibitor, coumarin-3-phenylcarboxamide, has also been synthesized from coumarin-3-carboxylic acid obtained in the catalysis process. A detailed mechanism of action is also provided.

Full text of DOI:10.1021/acs.inorgchem.0c01178

pubs.acs.org/IC
Article
A Primary Amide-Functionalized Heterogeneous Catalyst for the
Synthesis of Coumarin-3-carboxylic Acids via a Tandem Reaction
Datta Markad, Sadhika Khullar, and Sanjay K. Mandal*
Cite This: https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A crystalline primary amide-based bifunctional
heterogeneous catalyst, {[Cd2(2-BPXG)(Fum)2(H2O)2]·2H2O}n
(1) (where, 2-BPXG = 2,2′-((1,4-phenylenebis(methylene))
bis((pyridin-2-ylmethyl)azanediyl)) diacetamide and Fum =
fumarate), has been developed for the one-pot synthesis of a series
of potentially biologically active coumarin-3-carboxylic acids at
room temperature via a Knoevenagel-intramolecular cyclization
tandem reaction. Catalyst 1 is prepared at room temperature from a
one-pot self-assembly process in 81% yield and high purity within a
few hours and has a ladder-like polymeric architecture based on
single-crystal X-ray diffraction. Additional characterization of 1
includes elemental analysis, infrared spectroscopy, thermogravi-
metric analysis, and powder X-ray diffraction. Based on the
optimized conditions, it is determined that 1 is highly efficient (conditions: 2 mol % catalyst, 3 h, and 26−28 °C in methanol) for
this reaction. Its recyclability up to five cycles without significant loss of activity and structural integrity is also demonstrated. Using
both electron-donating and electron-withdrawing substituents on the salicylaldehyde substrate, seven different derivatives of
coumarin-3-carboxylic acid were made. Additionally, the monoamine oxidase (MAO) inhibitor, coumarin-3-phenylcarboxamide, has
also been synthesized from coumarin-3-carboxylic acid obtained in the catalysis process. A detailed mechanism of action is also
provided.
Interestingly, coumarin-3-carboxylic acids (also known as
3-carboxycoumarins) have some specific applications in a wide
range of possibilities over other coumarin derivatives (esters
and amides). In particular, coumarin-3-carboxylic acid
derivatives are used (i) for the detection of hydroxyl radical
[·OH] in aqueous solution generated in chemical or γ radiation
processes,30 (ii) in treatment of neurological disorders such as
neuropathic pain, epilepsy and depression,31 and (iii) as
fluorescent probes and triplet oxygen sensitizers.32,33 Thus,
such chemicals can be considered as novel promising hits for
ensuing innovative work.
Numerous pathways are known in the literature for the
synthesis of coumarin-3-carboxylic acids.34−43 A two-step
method developed by Armstrong et al. in 1988 involved
Knoevenagel condensation of 2-methoxybenzaldehydes with
Meldrum’s acid in dimethylformamide (DMF) followed by
cyclization with H2SO4.34 A solid-phase version of the above
INTRODUCTION
■
Coumarins are a naturally occurring aromatic secondary unit
with a benzopyrone scaffold, which is observed as a structural
motif in numerous natural products. These have aroused
significant interests due to their bioactivity and pharmaco-
logical properties.1−6 Coumarin and their derivatives display a
wide variety of biological activities, such as antitumor,
anticoagulant, antispasmodic, antidiabetic, antibiotic, anti-
HIV-1, and antioxidant activities.4,5,7−14 Consequently, cou-
marins are used as synthetic building blocks in the
pharmaceutical industry; their use in material science, perfume,
agrochemical, food, and cosmetics industries are also noted.2
Some coumarin derivatives have also been used for the
fluorescence-based sensing of fluoride anions and other
chromogenic sensing.15,16 Their selective inhibition to mono-
amine oxidase (MAO) and potent inhibition to cancer cell
invasion in vitro and tumor growth in vivo have also been
reported.17,18 In particular, several 3-substituted coumarin
derivatives have been extensively studied as potent MAO and/
or acetylcholinesterase (AChE) inhibitors while a few have
been proposed for treating Alzheimer’s disease (Scheme
1).19−21 For the above-mentioned important uses, synthesis
of coumarins has been reported via Pechmann reaction,22
Perkin reaction,23 Claisen rearrangement,24,25 Knoevenagel
reaction,26 Reformatsky reaction,27 and Wittig reaction.28,29
Received: April 21, 2020
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
© XXXX American Chemical Society
Inorg. Chem. XXXX, XXX, XXX−XXX
A

Inorganic Chemistry
pubs.acs.org/IC
Article
targeted for catalysis because there are two main aspects in a
primary amide group: (a) it coordinates to the metal center
through oxygen, and (b) the uncoordinated −NH2 moiety can
act as a Brønsted base and provides hydrogen bonding sites
(Scheme 2). Thus, such bifunctional CPs are very useful for
Scheme 1. Naturally or Clinically Well-known Occurring
Compounds or Drugs Bearing
a
Scheme 2. Schematic Representation of Primary Amide-
functionalized Ligand 2-BPXG with Labelled Catalytic
Active Sites and Metal Coordinating Site
a
The coumarin nucleus is highlighted in blue.
reaction was carried out with excess of ZnO at 80 °C.35 In the
subsequent years, one-pot methods were developed involving
condensation of ortho-hydroxyarylaldehyde and Meldrum’s
acid under the following conditions, i.e., (a) a solid acid
catalyst under microwave irradiation,36,37 (b) grinding the
reaction mixture with ammonium acetate followed by leaving it
undisturbed overnight,38 (c) sodium azide (50 mol %) or
K2CO3 (20 mol %) in water for 20 h,39 and (d) piperidinium
acetate in ethanol under reflux conditions.40 In some processes,
heating the reaction mixture in an aqueous medium has been
found as an alternative to the use of a catalyst.41,42 Finally, a
solid-phase synthesis using ethylmalonate tethered to Wang
resin in pyridine as solvent was reported.43 However, there are
ample scopes to develop new types of cheap and metal-based
catalysts that could be easily recyclable (for a heterogeneous
system) and show a high efficiency (requiring low mol % of
catalysts) under mild conditions.
Coordination polymers (CPs) consisting of metal ions or
clusters (as nodes) and multitopic organic ligands and/or
linkers have well-defined diverse structures and are found to be
useful in gas separation and storage, sensors and luminescence,
drug storage and delivery, and catalysis.44−47 Their porous
nature with high surface areas and tunable functionality are
distinct relative to other porous materials.48,49 In particular,
CPs offer several advantages over other homogeneous and
heterogeneous catalyst systems.50−52 CPs with coordinatively
unsaturated metal centers and/or functional groups that are
strategically present in the linker/ligand systems can act as
heterogeneous catalysts. Catalytic reactions performed with
CPs have paramount importance in many organic reactions,
such as transesterification, oxidation, cyanosilylation, aldol
condensation, and many more.51,53,54 With so much interest in
CPs, the development of bifunctional CPs to carry out tandem
reactions is an unexplored field.55−57 To the best of our
knowledge, there is no report on catalytic Knoevenagel-
intramolecular cyclization tandem reaction to synthesize
coumarin-3-carboxylic acid using bifunctional CPs.
important reactions requiring a Brønsted base while their
exclusive involvement is responsible for hydrogen bond
donating (HBD) catalysis. For some time we have engaged
to design and synthesize new CPs with divalent metal ions
(Zn2+ or Cd2+) with bis(tridentate) primary amide-pyridyl
ancillary ligands and commonly used dicarboxylate linkers like
fumarate and 1,4-benzenedicarboxylate. Earlier we have
demonstrated the importance of the primary amide-function-
alized CPs to catalyze Knoevenagel condensation,58 Friedel−
Crafts alkylation,59 and Michael addition60 reactions. Interest-
ingly, it has been found that cadmium is preferred as the core
metal in the CPs for bifunctional catalysis because it can
provide more than six coordination sites, allowing a water
molecule to coordinate to it. Upon activation of the catalyst
due to loss of the coordinated water molecule, it provides a
coordinatively unsaturated Cd(II) center serving as a potential
Lewis acidic site. Thus, we chose to develop Cd-based
bifunctional catalysts for the proposed synthesis of coumarin-
3-carboxylic acids.
Herein, we report the use of a crystalline CP, {[Cd2(2-
BPXG)(Fum)2(H2O)2]·2H2O}n (1) (where, 2-BPXG = 2,2′-
((1,4-phenylenebis(methylene))bis((pyridin-2-ylmethyl)-
azanediyl))diacetamide and Fum = fumarate), as a highly
efficient and recyclable heterogeneous catalyst for the one-pot
synthesis of a series of coumarin-3-carboxylic acids at 26−28
°C via a Knoevenagel-intramolecular cyclization tandem
reaction (see Scheme 2 for the structure of 2-BPXG).
Furthermore, we have been able to synthesize coumarin-3-
phenylcarboxamide (Scheme 1), which is a clinically potent
and selective inhibitor for MAO-B and can be used in the
treatment of Alzheimer’s and Parkinson’s diseases.19,20
EXPERIMENTAL SECTION
Materials and Methods. All chemicals and solvents used in this
■
work were obtained from commercial sources. The 2-BPXG ligand
was made by the literature method.61 The H NMR spectra were
1
obtained in CDCl3 at 25 °C on a Bruker ARX-400 spectrometer. For
the elemental analysis (C, H, N) of 1, a Mettler CHNS analyzer was
used. Using a Shimadzu DTG-60H instrument, all thermogravimetric
analyses were carried out from 25 to 500 °C (at a heating rate of 10
In this regard, we have envisioned that primary amide-
functionalized ligands are good candidates for making
bifunctional CPs (where the metal center acts a Lewis acid)
B
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
°C/min) under dinitrogen atmosphere. Solid samples, prepared as
KBr pellets, were used to collect FTIR spectra in the 4000−400 cm−1
range on a PerkinElmer Spectrum I spectrometer. The amount of Cd
in the product was estimated by energy dispersive X-ray spectroscopy
(EDX, HORIBA EX-250, 15 kV) associated with field-emission
scanning electron microscopy (FESEM). Detailed procedures of
single crystal and powder X-ray diffraction are provided in the
Supporting Information.
organic solvents but displays reasonable thermal stability based
on the thermogravimetric analysis (Figure S2). Based on the
multistep decomposition process, the first step involves the loss
of lattice and coordinated water molecules followed by the loss
of fumarate linker and ligand. A loss of ∼10.77% between 30
and 180 °C corresponds to two lattice and two coordinated
water molecules (ca. 10.86%) in the first step. The calculated
value (66.39%) matches well with the experimental value
(∼66.30%) for the second weight loss between 200 and 500
°C. This observation confirms the strong hydrogen bonding of
lattice water molecules with amide functionality as well as with
the coordinated water molecules. Further, the activated sample
of 1 does not show any weight loss in the temperature range of
30−200 °C, confirming the absence of solvent molecules, and
it is stable up to 250 °C (vide infra). In order to confirm that
single crystals (obtained from the layering method; see
Experimental Section for details) used for determining the
structure of 1 are the same as the bulk material synthesized at
room temperature, the similarity between experimental and
simulated (from the single-crystal data) powder XRD patterns
was checked (Figure 1). This further confirms the phase purity
of bulk 1.
Synthesis of {[Cd2(2-BPXG)(Fum)2(H2O)2]·2H2O}n (1). In a 10 mL
round-bottom flask (RBF), Cd(OAc)2·2H2O (30.8 mg, 0.11 mmol)
and 2-BPXG (25 mg, 0.057 mmol) were mixed in 4 mL of ethanol
with stirring to obtain a clear solution. To this mixture, a clear
solution of Na2fumarate (18.5 mg, 0.11 mmol) dissolved in 4 mL of
water was added while stirring continuously. With the appearance of a
precipitate, the reaction was stopped after stirring for another 4 h at
room temperature to collect an off-white solid. For isolating it, the
solid was filtered and washed with ethanol and vacuum-dried. Yield:
45 mg (81%). Anal. calcd (%) for C32H40N6Cd2O14 (MW 960.07): C,
40.14; H, 4.21; N, 8.78. Found: C, 40.39; H, 4.78; N, 8.36. Selected
FTIR peaks (KBr, cm−1): 3425 (br), 3186 (br), 1670 (s), 1576 (s),
1382 (s), 1135 (m), 1202 (w), 1005 (s), 806 (m), 768 (s), 679 (s).
For obtaining single crystals of 1, a direct layering method was used; a
clear solution of Cd(OAc)2·2H2O (12.4 mg, 0.046 mmol) and 2-
BPXG (10 mg, 0.023 mmol) in 0.8 mL of ethanol/water (1:1, v/v)
taken in a thin test tube was layered carefully over a solution of
disodium fumarate (7.4 mg, 0.046 mmol in 0.8 mL of water) with a
middle layer of 0.2 mL of ethanol and water (1:1, v/v). After the tube
was kept undisturbed for a week, colorless block-shaped crystals were
obtained.
General Protocol for Catalysis. All catalytic reactions were
carried out in screw cap glass vials with constant stirring. A mixture of
a salicylaldehyde (12.2 mg, 0.10 mmol), Meldrum’s acid (21.6 mg,
0.15 mmol), and fine powder of activated 1 (1.8 mg, 2 mol %) in
MeOH (1 mL) was stirred at room temperature (26−28 °C) for the
indicated time, and the catalyst was removed by centrifugation and
filtration at room temperature. Upon evaporation of the solvent, the
crude product was dissolved in DMSO-d6 to determine its yield using
1H NMR spectroscopy. For recycling the catalyst in subsequent runs,
it was separated by centrifugation and simple filtration followed by
washing with MeOH and drying in a vacuum oven.
RESULTS AND DISCUSSION
■
Figure 1. Simulated and experimental PXRD patterns of 1.
Synthesis and Characterization. Treatment of a mixture
of Cd(OAc)2·2H2O and 2-BPXG (in a 2:1 ratio) in EtOH with
an aqueous solution of sodium fumarate at 26−28 °C
generates 1 as a white precipitate in 81% yield (Scheme 3).
Structure Description. Based on the single-crystal X-ray
diffraction study, 1 crystallizes in the monoclinic space group
P21/n. The crystallographic information pertaining to data
collection and structure refinement has been provided in Table
1. In the asymmetric unit of 1, one Cd(II) center, one fumarate
linker, one-half of 2-BPXG ligand, one coordinated water, and
one lattice water molecule are present. The Cd(II) center
adopts a seven-coordinated distorted pentagonal bipyramidal
geometry with an N2O5 environment. Each Cd(II) center is
coordinated by one oxygen and two nitrogen atoms from one-
half of the 2-BPXG ligand, three oxygen atoms from two
fumarates, and one oxygen atom from water (Figure S3).
Compared to other Cd compounds in the literature, there is
some deviation in the Cd−N and Cd−O distances that are in
the range of 2.304(2)−2.334(2) Å and 2.273(2)−2.417(3) Å,
respectively.64 Selected bond distances and angles are reported
in Table S1, Supporting Information. The fumarate linker
shows two types of binding modes, where one end binds to the
Cd(II) center in a bidentate chelating fashion and the other
end binds in a monodentate fashion.
Scheme 3. Synthesis of 1
Using the solid-state FTIR spectroscopy, the presence of
both lattice and coordinated water molecules is established by
observing a broad peak at 3425 cm−1 and a shoulder at 3186
cm−1 as the respective O−H stretching frequency. On the
other hand, the difference in asymmetric (1576 cm−1) and
symmetric (1382 cm−1) stretching frequencies (194 cm−1) for
the carboxylate group of fumarate confirms its bidentate
chelating/monodentate binding mode in 1, while a stretching
frequency at 1670 cm−1 shows the binding of the primary
amide functionality to the metal center62,63 (Figure S1). This is
further confirmed in its crystal structure (vide infra). As
expected for polymeric CPs, 1 is found to be insoluble in all
Based on the connectivity of Cd2(2-BPXG) units with
fumarate linkers, 1 has a 1D ladder-like structure, where two
Fum-Cd-Fum chains form its side rails with 2-BPXG as the
C
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
metal center), 1 was kept under vacuum at 120 °C for 5 h.
For such activation of 1, there was no loss of its structural
integrity based on the comparison of FTIR spectra and TGA
profiles for as-synthesized 1 and activated 1 (Figures S5 and
S6, respectively; also see the section for its stability after
catalysis by FTIR and PXRD). A typical reaction is performed
by mixing salicylaldehyde (0.1 mmol), Meldrum’s acid (0.15
mmol), and 1 (2 mol %) in 1 mL of methanol with constant
stirring at 26−28 °C for a particular time. The spent catalyst
was separated from the filtrate by centrifugation followed by
filtration. The crude product that was obtained upon
evaporation of the solvent under vacuum was dissolved in
Table 1. Crystallographic Data and Structure Refinement
Parameters for 1 and C-3-CA
compound
chemical formula
1
C-3-CA
C14H8O4
240.2
C16H20CdN3O7
478.75
100(2)
0.71073
monoclinic
P21/n
14.441(4)
9.215(2)
14.659(4)
90
formula weight (g/mol)
temperature (K)
wavelength (Å)
crystal system
space group
a (Å)
b (Å)
c (Å)
α (deg)
296(2)
0.71073
monoclinic
P21/c
5.313(12)
9.547(2)
18.515(5)
90
1
DMSO-d6 to determine the percent conversion by H NMR
spectroscopy (Figure S7).
β (deg)
γ (deg)
113.706(15)
90
90.268(8)
90
For developing optimized conditions, various solvents were
screened in this reaction. For a fixed period of 6 h, the percent
conversion followed the following order: methanol >
acetonitrile > tetrahydrofuran ≫ ethyl acetate ≫ chloroform
(Table 2, entries 1−5). In methanol, 100% conversion was
observed after 6 h, as no trace amount of aldehyde can be
detected by 1H NMR spectroscopy. The solvent screening also
demonstrates that methanol is a better solvent than other
organic solvents. The time dependency of the reaction was
studied with methanol as the solvent (Table 2, entries 6−12),
where the conversions are 54% and 86% for 15 min and 2 h,
respectively. In Figure 4, percent conversion versus time for
the reaction is presented; the optimized reaction time is found
to be 3 h.
Control experiments without 1 and three components of 1,
i.e., Cd(OAc)2·2H2O, 2-BPXG, and fumaric acid, were also
conducted (Table 2, entries 13−16). Interestingly, there was
no reaction without 1 while only 2% conversion was observed
with fumaric acid. Similarly, with Cd(OAc)2·2H2O and 2-
BPXG only 15% and 16% conversion was observed,
respectively.
For organic transformations with solid catalysts, it is
important to prove that no part of its active sites becomes
soluble in the liquid phase of the reaction mixture for claiming
a true heterogeneous process.66−69 In order to prove no
leaching of the catalyst into the organic phase and thus the true
heterogeneous nature of the catalyst, a control experiment was
conducted. Upon stirring the reaction mixture for 30 min (ca.
60% conversion of salicylaldehyde was observed), the catalyst
was filtered out from it. Whereupon, the reaction mixture was
stirred further for 150 min under the same reaction conditions
but no progress in product conversion was observed.
Combining these results, it is demonstrated that for the
Z
4
4
V (Å3)
1786.1(8)
1.78
939.2(4)
1.699
density (g/cm3)
μ (mm−1
F(000)
)
1.268
964
0.126
496
theta (deg) range for data coll.
reflections collected
independent reflections
reflections with I > 2σ(I)
Rint
1.67 to 25.50
12016
3325
2624
0.0568
251
1.003
0.0350/0.0713
0.0515/0.0766
2.20 to 24.99
16158
1645
1112
0.0497
167
1.021
0.0439/0.1096
0.0685/0.1263
no. of parameters refined
GOF on F2
a
b
final R1 /wR2 (I > 2σ(I))
R1/wR2 (all data)
largest diff. peak and hole (eÅ−3
)
0.720/−0.395
0.235/−0.216
a
b
R1 = ∑||F0| − |Fc||/∑|F0|. wR2 = [∑w(F0 − Fc2)2/∑w(F0 )2]1/2
2
2
2
2
where w = 1/[σ2(F0 ) + (aP)2 + bP], P = (F0 + 2Fc2)/3.
steps (Figure 2). Thus, the rectangular section, containing four
Cd centers at the corners, of the ladder has a dimension of
9.215 Å × 12.996 Å (the distance between two benzene rings
of 2-BPXG and two fumarate linkers, respectively, Figure S4).
Two such 1D ladders are involved in supramolecular
association through moderate π−π interactions65 between
two corresponding benzene and pyridine rings with a
centroid−centroid distance of 3.945 Å (Figure 3).
Catalytic Activity. For showcasing the heterogeneous
catalysis behavior of 1, an activated solid was used in the
Knoevenagel-intramolecular cyclization tandem reaction of
Meldrum’s acid (2,2-dimethyl-1,3-dioxane-4,6-dione) with
various salicylaldehyde derivatives (Table 2). In order to
obtain activated 1 (generating coordinatively unsaturated
Figure 2. View of the extended 1D ladder-like structure and coordination environment around the hepta-coordinated Cd(II) center of 1. Color
codes: cadmium, green; carbon, gray; nitrogen, blue; and oxygen, red. Hydrogen atoms of carbon are omitted for clarity.
D
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
Figure 3. 2D supramolecular assembly formed by two 1D ladders of 1 through π−π interaction represented by blue arrows.
Table 2. Optimization of Knoevenagel-Intramolecular Cyclization Tandem Reaction between Meldrum’s Acid and
Salicyladehyde at 26−28 °C
a
b
entry
catalyst
time
6 h
6 h
6 h
6 h
solvent
catalyst (mol %)
conversion (%)
TON
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
1
1
1
THF
2
2
2
2
2
2
2
2
2
2
2
2
---
2
68
82
5
34
41
2.5
50
15
27
30
33.5
35.5
39.5
43
50
---
7.5
16
1
CH3CN
CHCl3
MeOH
EtOAc
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
100
30
54
60
67
71
79
86
100
---
6 h
15 min
30 min
45 min
1 h
1.5 h
2 h
3 h
3 h
3 h
3 h
9
10
11
12
13
14
15
16
---
Cd(OAc)2
2-BPXG
H2Fum
15
16
2
1
2
3 h
MeOH
a
b
1
Average conversion for a set of triplicate runs, determined by H NMR spectroscopy. Number of moles of product per mole of catalyst.
synthesis of coumarin-3-carboxylic acid a catalyst 1 is essential,
and no leaching of active cadmium species into the liquid
phase has occurred during the reaction (Figure 4).
Additionally, the amount of cadmium in the dried filtrate
(after separating the catalyst from the reaction mixture and
removal of solvent) was determined by energy dispersive X-ray
spectrometry (EDX) associated with field-emission scanning
electron microscopy (FESEM). Since there was no detectable
cadmium found in the product (Figure S8), it further confirms
that the reaction is heterogeneous in nature.
Using optimized reaction conditions (2 mol % of 1, 1 mL of
MeOH, 0.15 mmol of Meldrum’s acid, and 0.1 mmol of
aldehyde; 3 h at 26−28 °C), a variety of salicylaldehydes were
then employed as substrates to investigate the scope of the
substrates, where both electron-donating and electron-with-
drawing substituents, namely, methoxy, bromo, chloro, nitro,
and benzo, reacted smoothly with Meldrum’s acid to afford the
corresponding coumarin derivatives (Table 3 and Figure S9).
It is to be noted that 2-hydroxy-1-naphthaldehyde provides a
slightly lower yield (90%) compared to salicylaldehyde (98%)
Figure 4. Plot of percent conversion vs time for 1; the red line is for
completion of the reaction with catalyst, and the green line after 30
min, when the catalyst was removed, is to demonstrate its
heterogeneous nature.
E
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
Table 3. Substrate Scope for the Knoevenagel-Intramolecular Cyclization Tandem Reaction to Synthesize Coumarin-3-
a
carboxylic Acid Derivatives
a
Reaction conditions: Aldehyde (0.1 mmol), Meldrum’s acid (0.15 mmol), and 1 (2 mol %) in MeOH (1 mL) at 26−28 °C; reaction time, 3 h.
b
Isolated yield after purification.
under the same condition due to an increase in size. The
identity and purity of all products in Table 3, except the 3-
chloro derivative, are confirmed by matching their melting
points with the literature values. For the new 3-chloro
reaction (Figures S13 and S14). Catalyst 1 was recovered to
reuse in subsequent runs under the same reaction conditions.
For five consecutive runs, its catalytic activity was monitored.
After five cycles a conversion >90% can be achieved (the
difficulty in recovering the catalyst that is used in very small
quantity plays a role in the reduction of this percentage after a
few cycles). This indicates a minor loss of catalytic activity of 1
during its recycling (Figure 6).
1
derivative, further characterization by H and 13C NMR and
FTIR spectroscopy was done (Figures S10−S12). On the
other hand, a single crystal of 3-oxo-3H-benzo[f]chromene-2-
carboxylic acid (C-3-CA), the product in entry #7, obtained
from the slow evaporation of a methanol solution was used to
determine its 3D structure (Table 1 and Figure 5).
Figure 5. Molecular structure of 3-oxo-3H-benzo[f ]chromene-2-
carboxylic acid. Non-hydrogen atoms are represented by ellipsoids
with 30% probability. Hydrogen atoms are shown as spheres with
random radius.
Figure 6. Plot of percent conversion for five consecutive cycles of the
tandem reaction of salicylaldehyde and Meldrum’s acid catalyzed by 1.
An important derivative of coumarin-3-carboxylic acid,
coumarin-3-phenylcarboxamide, was synthesized to show the
usefulness of our catalytic process (Scheme 4). In the
literature, Liu et al.20,70 and Borges et al.71 have reported a
series of coumarin-3-phenylcarboxamide derivatives in four
and three time-consuming steps, respectively. Here, we have
established its synthesis in two steps, where coumarin-3-
carboxylic acid is a key intermediate. By following the
previously reported procedure,72 coumarin-3-phenylcarboxa-
mide was synthesized from coumarin-3-carboxylic acid as a
Compared to homogeneous catalysis, there are several
advantages, like easy catalyst separation, recovery, and
recycling, in the case of heterogeneous catalysis. In order to
examine the recoverability and reusability of 1, its isolation at
the completion of a run via filtration and washing with
methanol was followed by an activation in a vacuum oven at
120 °C for 5 h. The structural integrity of 1 was found to be
intact during the catalysis by comparing its FTIR spectra and
powder X-ray diffraction patterns obtained before and after the
F
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
activated powder sample of 1 was kept in D2O for 12 h to
do a quantitative exchange of H2O by D2O. The ν(O−D) stretch
in the D2O-exchanged 1 was observed at ca. 2520 cm−1 with a
shift of ca. 913 cm−1 compared to the ν(O−H) stretch of water in
1 (Figure S16) without any significant changes in other
spectral features, confirming the stability of 1. Moreover,
activated 1 was stirred in a CH2Cl2 solution containing
Meldrum’s acid at 27 °C for a few hours. Based on the FTIR
spectra shown in Figure S17, for the Meldrum’s acid before
and after interaction with 1, two major changes are observed
through the appearance of new peaks at ca. 1600 cm−1
corresponding to the CC stretch and at ca. 1323 cm−1
corresponding to the CO stretch of the CCO group.
This experiment clearly demonstrates that 1 is also acting as
a Brønsted base. It can be concluded that (a) an aldehydic
substrate first is activated through the Lewis acidic metal center
of 1, and (b) simultaneously, an activation of the nucleophilic
center of Meldrum’s acid is promoted by the Brønsted basic
site of 1 before it reacts with the aldehydic substrates to
produce the desired coumarin derivatives.
Scheme 4. Synthesis of Coumarin-3-phenylcarboxamide: (i)
Aniline, EDC, DMAP, DCM, 27 °C, and 4 h
yellow solid in an overall 71% yield (for detailed synthetic
1
procedure and H NMR spectrum, see Figure S15).
Mechanistic Study. A plausible mechanism for this
reaction catalyzed by 1 is presented in Scheme 5. In this
overall process, the first step is believed to be the interaction of
the coordinatively unsaturated cadmium center (Lewis acid
site) in 1 with the carbonyl group of the aldehyde, polarizing
this group. The increase in the electrophilic character of the
carbonylic carbon atom thus favors the attack from the
Meldrum’s acid. Similarly, through the abstraction of a proton
from the Meldrum’s acid, the Brønsted basic site (−NH2
moiety in the primary amide group) in 1 helps to generate the
corresponding nucleophilic species for connecting with the
carbonyl group of the aldehyde, which is followed by the
subsequent dehydration to form a CC bond. Subsequently,
the formation of CC and penultimate intramolecular
cyclization followed by protonation gives the desired
cumarin-3-carboxylic acid product. Thus, the substrates
approach the catalytic active sites of 1 (Cd(II) and CONH2
moiety) on the surface. The labile nature of the coordinated
H2O molecule in 1 (e.g., a substrate to replace it) was
investigated by a D2O exchange experiment, where the
CONCLUSIONS
■
In summary, we demonstrated the use of a primary amide-
functionalized Cd(II) CP, {[Cd2(2-BPXG)(Fum)2(H2O)2]·
2H2O}n (1), as an effective bifunctional heterogeneous catalyst
in the important C−C bond forming reaction, namely the
Knoevenagel-intramolecular cyclization tandem reaction, to
synthesize bioactive coumarin-3-carboxylic acids. For this, two
important points should be noted: (a) the catalyst was
prepared at room temperature from a one-pot self-assembly
process in an excellent yield and purity within few hours, and
(b) the catalyst was determined to be highly efficient for this
Scheme 5. Plausible Mechanism for the Knoevenagel-Intramolecular Cyclization Tandem Reaction Catalyzed by 1
G
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
(3) Lee, Y. T.; Das, U.; Chen, Y. R.; Lee, C. J.; Chen, C. H.; Yang,
M. C.; Lin, W. Enantioselective Synthesis of Coumarin Derivatives
Catalyzed by Primary Amines. Adv. Synth. Catal. 2013, 355, 3154−
3160.
(4) Fylaktakidou, K. C.; Hadjipavlou-Litina, D. J.; Litinas, K. E.;
Nicolaides, D. N. Natural and Synthetic Coumarin Derivatives with
Anti-Inflammatory/Antioxidant Activities. Curr. Pharm. Des. 2004, 10,
3813−3833.
(5) Melliou, E.; Magiatis, P.; Mitaku, S.; Skaltsounis, A.-L.; Chinou,
E.; Chinou, I. Natural and Synthetic 2,2-Dimethylpyranocoumarins
with Antibacterial Activity. J. Nat. Prod. 2005, 68, 78−82.
(6) Widelski, J.; Melliou, E.; Fokialakis, N.; Magiatis, P.; Glowniak,
K.; Chinou, I. Coumarins from the Fruits of Seseli devenyense. J. Nat.
Prod. 2005, 68, 1637−1641.
(7) O’Reilly, R. A.; Aggeler, P. M.; Leong, L. S. Studies on the
Coumarin Anticoagulant Drugs: The Pharmacodynamics of Warfarin
in man. J. Clin. Invest. 1963, 42, 1542−1551.
(8) Vasconcelos, J. F.; Teixeira, M. M.; Barbosa-Filho, J. M.; Agra,
M. F.; Nunes, X. P.; Giulietti, A. M.; Ribeiro-dos-Santos, R.; Soares,
M. B. P. Effects of umbelliferone in a murine model of allergic airway
inflammation. Eur. J. Pharmacol. 2009, 609, 126−131.
(9) Khan, K. M.; Saify, Z. S.; Khan, M. Z.; Zia-Ullah; Choudhary, M.
I.; Atta-ur-Rahman; Perveen, S.; Chohan, Z. H.; Supuran, C. T.
Synthesis of Coumarin Derivatives with Cytotoxic, Antibacterial and
Antifungal Activity. J. Enzyme Inhib. Med. Chem. 2004, 19, 373−379.
(10) Chimenti, F.; Bizzarri, B.; Bolasco, A.; Secci, D.; Chimenti, P.;
Carradori, S.; Granese, A.; Rivanera, D.; Lilli, D.; Scaltrito, M. M.;
Brenciaglia, M. I. Synthesis and in vitro selective anti-Helicobacter
pylori activity of N-substituted-2-oxo-2H-1-benzopyran-3-carboxa-
mides. Eur. J. Med. Chem. 2006, 41, 208−212.
(11) Salar, U.; Khan, K. M.; Fakhri, M. I.; Hussain, S.; Tauseef, S.;
Ameer, S.; Wadood, A.; Khan, H.; Perveen, S. 1,1’-Carbon-
yldiimidazole (CDI) Mediated Facile Synthesis, Structural Character-
ization, Antimicrobial Activity, and in-silico Studies of Coumarin- 3-
carboxamide Derivatives. Med. Chem. (Sharjah, United Arab Emirates)
2018, 14, 86−101.
reaction (conditions: 2 mol % catalyst, 3 h, and 26−28 °C in
methanol). Based on the ladder-like structure of 1 determined
by single-crystal X-ray diffraction, it is proposed that the
substrates approach the catalytic active sites of 1 (Cd(II) and
CONH2 moiety) on the surface. Its heterogeneous nature was
demonstrated by no leaching of the catalyst through the EDX
study. Its broad substrate scope with both electron-donating
and electron-withdrawing substituents and recyclability were
also noteworthy. Therefore, this new approach for the
synthesis of lactone-based bioactive compounds must be
taken as a path forward for the construction of different
heterogeneous catalytic systems. Furthermore, development of
new chiral catalysts is also a goal of our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c01178.
Experimental details, characterization (FTIR, TGA,
SCXRD, and PXRD), and NMR spectra for catalysis
(PDF)
Accession Codes
CCDC 1873852−1873853 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
Sanjay K. Mandal − Department of Chemical Sciences, Indian
Institute of Science Education and Research Mohali, Mohali,
Punjab 140306, India; orcid.org/0000-0002-5045-6343;
Email: sanjaymandal@iisermohali.ac.in
(12) Zhang, Z.; Bai, Z.-W.; Ling, Y.; He, L.-Q.; Huang, P.; Gu, H.-
X.; Hu, R.-F. Design, synthesis and biological evaluation of novel
furoxan-based coumarin derivatives as antitumor agents. Med. Chem.
Res. 2018, 27, 1198−1205.
(13) Peng, X.-M.; L.V. Damu, G.; He Zhou, C. Current
developments of coumarin compounds in medicinal chemistry.
Curr. Pharm. Des. 2013, 19, 3884−3930.
Authors
Datta Markad − Department of Chemical Sciences, Indian
Institute of Science Education and Research Mohali, Mohali,
Punjab 140306, India; orcid.org/0000-0001-6447-7922
Sadhika Khullar − Department of Chemistry, Dr B R Ambedkar
National Institute of Technology Jalandhar, Punjab 144011,
India
(14) Emami, S.; Dadashpour, S. Current developments of coumarin-
based anti-cancer agents in medicinal chemistry. Eur. J. Med. Chem.
2015, 102, 611−630.
(15) Cao, X.; Lin, W.; Yu, Q.; Wang, J. Ratiometric Sensing of
Fluoride Anions Based on a BODIPY-Coumarin Platform. Org. Lett.
2011, 13, 6098−6101.
(16) Choi, M. G.; Hwang, J.; Moon, J. O.; Sung, J.; Chang, S.-K. Hy
drazine -Selective Chromogenic and Fluorogenic Probe Based on
Levulinated Coumarin. Org. Lett. 2011, 13, 5260−5263.
(17) Chimenti, F.; Secci, D.; Bolasco, A.; Chimenti, P.; Granese;
Befani, A. O.; Turini, P.; Alcaro, S.; Ortuso, F. Inhibition of
monoamine oxidases by coumarin-3-acyl derivatives: biological
activity and computational study. Bioorg. Med. Chem. Lett. 2004, 14,
3697−3703.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.0c01178
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(18) Kempen, I.; Hemmer, M.; Counerotte, S.; Pochet, L.; de Tullio,
Funding for this work was provided by IISER Mohali, to
S.K.M. and the UGC of India to D.M. (a research fellowship).
Facilities at IISER Mohali (X-ray, NMR, and SEM), and at
CIL, NIPER Mohali, are gratefully acknowledged.
̈
P.; Foidart, J.-M.; Blacher, S.; Noel, A.; Frankenne, F.; Pirotte, B. 6-
Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a
new approach of the treatment of cancer cell invasion and metastasis.
Eur. J. Med. Chem. 2008, 43, 2735−2750.
́
(19) Vina, D.; Matos, M. J.; Yanez, M.; Santana, L.; Uriarte, E. 3-
̃ ̃
REFERENCES
Substituted coumarins as dual inhibitors of AChE and MAO for the
treatment of Alzheimer’s disease. MedChemComm 2012, 3, 213−218.
(20) He, X.; Chen, Y.-Y.; Shi, J.-B.; Tang, W.-J.; Pan, Z.-X.; Dong,
Z.-Q.; Song, B.-A.; Li, J.; Liu, X.-H. New coumarin derivatives:
Design, synthesis and use as inhibitors of hMAO. Bioorg. Med. Chem.
2014, 22, 3732−3738.
■
(1) Murray, R. D. H.; Mendez, J.; Brown, S. A. The Natural
Coumarins: Occurrence, Chemistry and Biochemistry; John Wiley &
Sons: New York, 1982.
(2) O’Kennedy, R.; Thornes, R. D. Coumarins: Biology, Applications
and Mode of Action; John Wiley and Sons: Chichester, 1997.
H
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
́
(21) Robert, S.; Bertolla, C.; Masereel, B.; Dogne, J.-M.; Pochet, L.
Novel 3-Carboxamide-coumarins as Potent and Selective FXIIa
Inhibitors. J. Med. Chem. 2008, 51, 3077−3080.
(43) Watson, B. T.; Christiansen, G. E. Solid phase synthesis of
substituted coumarin-3-carboxylic acids via the Knoevenagel con-
densation. Tetrahedron Lett. 1998, 39, 6087−6090.
(44) Alhamami, M.; Doan, H.; Cheng, C.-H. A Review on Breathing
Behaviors of Metal-Organic-Frameworks (MOFs) for Gas Adsorp-
tion. Materials 2014, 7, 3198−3250.
(22) Heravi, M. M.; Khaghaninejad, S.; Mostofi, M. Adv. Heterocycl.
Chem.; Academic Press: 2014; Vol. 112, pp 1−50.
(23) Johnson, J. R. In Organic Reactions; John Wiley & Sons, Inc.:
Hoboken, NJ, USA, 2011; pp 210−265.
̈
(45) Schroder, M. Functional Metal-Organic Frameworks: Gas
Storage, Separation and Catalysis; Springer: Berlin, 2010; Vol. 293.
(46) Hu, Z.; Deibert, B. J.; Li, J. Luminescent metal−organic
frameworks for chemical sensing and explosive detection. Chem. Soc.
Rev. 2014, 43, 5815−5840.
(24) Cairns, N.; Harwood, L. M.; Astles, D. P. On the intrinsic and
carbon-induced selectivity of platinum catalysts. J. Chem. Soc., Chem.
Commun. 1986, 1264−1266.
(25) Majumdar, K. C.; Debnath, P.; Maji, P. K. Thiophenol-
catalyzed Claisen rearrangement and radical cyclization: formation of
furo- and pyrano-coumarin derivatives. Tetrahedron Lett. 2007, 48,
5265−5268.
(47) Cook, T. R.; Zheng, Y.; Stang, P. J. Metal-organic frameworks
and self-assembled supramolecular coordination complexes: compar-
ing and contrasting the design, synthesis, and functionality of metal-
organic materials. Chem. Rev. 2013, 113, 734−777.
(26) Vekariya, R. H.; Patel, H. D. Recent Advances in the Synthesis
of Coumarin Derivatives via Knoevenagel Condensation: A Review.
Synth. Commun. 2014, 44, 2756−2788.
(27) Shriner, R. L. In Organic Reactions; John Wiley & Sons, Inc.:
Hoboken, NJ, USA, 2011; pp 1−37.
(28) Maes, D.; Vervisch, S.; Debenedetti, S.; Davio, C.; Mangelinckx,
S.; Giubellina, N.; De Kimpe, N. Kimpe, Synthesis and structural
revision of naturally occurring ayapin derivatives. Tetrahedron 2005,
61, 2505−2511.
(29) Ishii, H.; Kaneko, Y.; Miyazaki, H.; Harayama, T. A Convenient
Synthesis of a Simple Coumarin. Chem. Pharm. Bull. 1991, 39, 3100−
3102.
(30) Manevich, Y.; Held, K. D.; Biaglow, J. E. Coumarin-3-
Carboxylic Acid as a Detector for Hydroxyl Radicals Generated
Chemically and by Gamma Radiation. Radiat. Res. 1997, 148, 580−
591.
(31) Irvine, M. W.; Costa, B. M.; Volianskis, A.; Fang, G.; Ceolin,
G.; Collingridge, G. L.; Monaghan, D. T.; Jane, D. E. Coumarin-3-
carboxylic acid derivatives as potentiators and inhibitors of
recombinant and native N-methyl-D-aspartate receptors. Neurochem.
Int. 2012, 61, 593−600.
(32) Peroni, E.; Caminati, G.; Baglioni, P.; Nuti, F.; Chelli, M.;
Papini, A. M. A new lipophilic fluorescent probe for interaction
studies of bioactive lipopeptides with membrane models. Bioorg. Med.
Chem. Lett. 2002, 12, 1731−1734.
(48) Qin, J.; Yuan, S.; Wang, Q.; Alsalme, A.; Zhou, H.-C. Mixed-
linker strategy for the construction of multifunctional metal−organic
frameworks. J. Mater. Chem. A 2017, 5, 4280−4291.
(49) Rowsell, J. L. C.; Yaghi, O. M. Metal−organic frameworks: a
new class of porous materials. Microporous Mesoporous Mater. 2004,
73, 3−14.
̌
(50) Dhakshinamoorthy, A.; Opanasenko, M.; Cejka, J.; Garcia, H.
Metal Organic Frameworks as Solid Catalysts in Condensation
Reactions of Carbonyl Groups. Adv. Synth. Catal. 2013, 355, 247−
268.
(51) Valvekens, P.; Vermoortele, F.; De Vos, D. De Metal−organic
frameworks as catalysts: the role of metal active sites. Catal. Sci.
Technol. 2013, 3, 1435−1445.
(52) Farrusseng, D. Metal-Organic Frameworks: Applications from
Catalysis to Gas Storage; Wiley-VCH: 2011.
̌
(53) Dhakshinamoorthy, A.; Opanasenko, M.; Cejka, J.; Garcia, H.
Metal organic frameworks as heterogeneous catalysts for the
production of fine chemicals. Catal. Sci. Technol. 2013, 3, 2509−2540.
(54) 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.
(55) Srirambalaji, R.; Hong, S.; Natarajan, R.; Yoon, M.; Hota, R.;
Kim, Y.; Ho Ko, Y.; Kim, K. Tandem catalysis with a bifunctional site-
isolated Lewis acid−Brønsted base metal−organic framework, NH2-
MIL-101(Al). Chem. Commun. 2012, 48, 11650−11652.
(56) Park, J.; Li, J.-R.; Chen, Y.-P.; Yu, J.; Yakovenko, A. a.; Wang, Z.
U.; Sun, L.-B.; Balbuena, P. B.; Zhou, H.-C. A versatile metal−organic
framework for carbon dioxide capture and cooperative catalysis.
Chem. Commun. 2012, 48, 9995−9997.
(57) Li, B.; Zhang, Y.; Ma, D.; Li, L.; Li, G.; Li, G.; Shi, Z.; Feng, S.
A strategy toward constructing a bifunctionalized MOF catalyst: post-
synthetic modification of MOFs on organic ligands and coordinatively
unsaturated metal sites. Chem. Commun. 2012, 48, 6151−6153.
(58) Markad, D.; Khullar, S.; Mandal, S. K. Engineering a Nanoscale
Primary Amide-Functionalized 2D Coordination Polymer as an
Efficient and Recyclable Heterogeneous Catalyst for the Knoevenagel
Condensation Reaction. ACS Appl. Nano Mater. 2018, 1, 5226−5236.
(59) Markad, D.; Mandal, S. K. 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. ACS Catal. 2019, 9, 3165−3173.
(60) Markad, D.; Khullar, S.; Mandal, S. K. Design and
Development of a Heterogeneous Catalyst for the Michael Addition
of Malononitrile to 2-Enoylpyridines: Influence of the Primary Amide
Decorated Framework on Catalytic Activity and Selectivity. Inorg.
Chem. 2019, 58, 12547−12554.
(61) Markad, D.; Mandal, S. K. An exploration into the amide−
pseudo amide hydrogen bonding synthon between a new coformer
with two primary amide groups and theophylline. CrystEngComm
2017, 19, 7112−7124.
(62) Nakamoto, K. Infrared and Raman Spectra of Inorganic and
Coordination Compounds; John Wiley & Sons, Inc.: Hoboken, NJ,
USA, 2008.
(33) Specht, D. P.; Martic, P. A.; Farid, S. Ketocoumarins: A new
class of triplet sensitizers. Tetrahedron 1982, 38, 1203−1211.
(34) Armstrong, V.; Soto, O.; Valderrama, J. A.; Tapia, R. Synthesis
of 3-Carboxycoumarins from O-Methoxybenzylidene Meldrum’s Acid
Derivatives. Synth. Commun. 1988, 18, 717−725.
(35) Rouessac, F.; Leclerc, A. An Efficient Preparation of
Coumarins. Synth. Commun. 1993, 23, 2709−2715.
(36) Sharma, D.; Kumar, S.; Makrandi, J. K. Water mediated Green
Synthesis of Coumarin-3-carboxylic acids under microwave irradiation
condition. Chem. Sci. Trans. 2013, 2, 403−406.
(37) Bandgar, B. P.; Uppalla, L. S.; Kurule, D. S. Solvent-free one-
pot rapid synthesis of 3-carboxycoumarins using focused microwaves.
Green Chem. 1999, 1, 243−245.
(38) Scott, J. L.; Raston, C. L. Solvent-free synthesis of 3-
carboxycoumarins. Green Chem. 2000, 2, 245−247.
(39) Brahmachari, G. Room Temperature One-Pot Green Synthesis
of Coumarin-3-carboxylic Acids in Water: A Practical Method for the
Large-Scale Synthesis. ACS Sustainable Chem. Eng. 2015, 3, 2350−
2358.
(40) Song, A.; Wang, X.; Lam, K. S. A convenient synthesis of
coumarin-3-carboxylic acids via Knoevenagel condensation of Mel-
drum’s acid with ortho-hydroxyaryl aldehydes or ketones. Tetrahedron
Lett. 2003, 44, 1755−1758.
(41) Deshmukh, M. N.; Burud, R.; Baldino, C.; Chan, P. C. M.; Liu,
J. A Practical and Environmentally Friendly Preparation of 3-
Carboxycoumarins. Synth. Commun. 2003, 33, 3299−3303.
(42) Maggi, R.; Bigi, F.; Carloni, S.; Mazzacani, A.; Sartori, G.
Uncatalysed reactions in water: Part 2.Part 1: ref. 1. Preparation of 3-
carboxycoumarins. Green Chem. 2001, 3, 173−174.
I
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
pubs.acs.org/IC
Article
(63) Deacon, G. Relationships between the carbon-oxygen
stretching frequencies of carboxylato complexes and the type of
carboxylate coordination. Coord. Chem. Rev. 1980, 33, 227−250.
(64) Hong, X.-J.; Wei, Q.; Cai, Y.-P.; Zheng, S.-R.; Yu, Y.; Fan, Y.-Z.;
Xu, X.-Y.; Si, L.-P. 2-Fold Interpenetrating Bifunctional Cd-Metal−
Organic Frameworks: Highly Selective Adsorption for CO2 and
Sensitive Luminescent Sensing of Nitro Aromatic 2,4,6-Trinitrophe-
nol. ACS Appl. Mater. Interfaces 2017, 9, 4701−4708.
(65) Janiak, C. A critical account on π−π stacking in metal
complexes with aromatic nitrogen-containing ligands. J. Chem. Soc.,
Dalton Trans. 2000, 3885−3896.
(66) Phan, N. T. S.; Jones, C. W. Highly accessible catalytic sites on
recyclable organosilane-functionalized magnetic nanoparticles: An
alternative to functionalized porous silica catalysts. J. Mol. Catal. A:
Chem. 2006, 253, 123−131.
(67) Sheldon, R. A.; Wallau, M.; Arends, I. W. C. E.; Schuchardt, U.
Heterogeneous Catalysts for Liquid-Phase Oxidations: Philosophers’
Stones or Trojan Horses? Acc. Chem. Res. 1998, 31, 485−493.
(68) Karami, B.; Farahi, M.; Khodabakhshi, S. Rapid Synthesis of
Novel and Known Coumarin-3-carboxylic Acids Using Stannous
Chloride Dihydrate under Solvent-Free Conditions. Helv. Chim. Acta
2012, 95, 455−460.
́
́
(69) Martínez, J.; Sanchez, L.; Perez, F. J.; Carranza, V.; Delgado, F.;
Reyes, L.; Miranda, R. Uncatalysed Production of Coumarin-3-
carboxylic Acids: A Green Approach. J. Chem. 2016, 2016, 1−6.
(70) Pan, Z.-X.; He, X.; Chen, Y.-Y.; Tang, W.-J.; Shi, J.-B.; Tang, Y.-
L.; Song, B.-A.; Li, J.; Liu, X.-H. New 2H-chromene-3-carboxamide
derivatives: Design, synthesis and use as inhibitors of hMAO. Eur. J.
Med. Chem. 2014, 80, 278−284.
(71) Fonseca, A.; Reis, J.; Silva, T.; Matos, M. J.; Bagetta, D.; Ortuso,
F.; Alcaro, S.; Uriarte, E.; Borges, F. Coumarin versus Chromone
Monoamine Oxidase B Inhibitors: Quo Vadis? J. Med. Chem. 2017,
60, 7206−7212.
(72) Fonseca, A.; Matos, M. J.; Vilar, S.; Kachler, S.; Klotz, K.-N;
Uriarte, E.; Borges, F. Coumarins and adenosine receptors: New
perceptions in structure-affinity relationships. Chem. Biol. Drug Des.
2018, 91, 245−256.
J
https://dx.doi.org/10.1021/acs.inorgchem.0c01178
Inorg. Chem. XXXX, XXX, XXX−XXX