Heterogenized Phosphinic Acid on UiO-66-NH2: A Bifunctional Catalyst for the Synthesis of Polyhydroquinolines

Article abstract of DOI:10.1007/s10562-021-03734-1

Abstract: The preparation and application of UiO-66-NH₂-bis(aminomethyl)-phosphinic acid are reported in this study. The supported phosphinic acid is designed via a multi-step post-synthesis modification of a Zr-based metal–organic framework (M

Full text of DOI:10.1007/s10562-021-03734-1

Catalysis Letters
https://doi.org/10.1007/s10562-021-03734-1
Heterogenized Phosphinic Acid on UiO‑66‑NH2: A Bifunctional Catalyst
for the Synthesis of Polyhydroquinolines
Saeed Askari1 · Mohammad Mehdi Khodaei1,2 · Mohammad Jafarzadeh1,2
Received: 1 March 2021 / Accepted: 8 July 2021
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021
Abstract
The preparation and application of UiO-66-NH2-bis(aminomethyl)-phosphinic acid are reported in this study. The supported
phosphinic acid is designed via a multi-step post-synthesis modifcation of a Zr-based metal–organic framework (MOF),
UiO-66-NH2. The MOF is initially functionalized with ethylamine, followed by formaldehyde (formation of imine group),
and fnally with hypophosphorous acid to generate UiO-66-NH–CH2CH2N(CH2PO2H2)2. The modifed MOF is characterized
by diferent techniques such as XRD, SEM–EDS, FT-IR, TGA, and porosimetry. The modifed MOF is efciently used as
a multifunctional heterogeneous catalyst (available Brønsted/Lewis acid sites and Lewis base site) in the multicomponent
reaction of Hantzsch. A synergistic efect between the phosphinic acid and the support is observed for the synthesis of poly-
hydroquinolines. The catalyst is easily recycled and successfully reused several times.
Graphic Abstract
An acidic-basic heterogeneous catalyst was prepared and characterized, and the performance of the catalyst was investigated
for the synthesis of polyhydroquinoline derivatives.
O
o C
70
R-CHO
O
O
o C
P
OH
OH
70
O
O
o C
NH
H
R
70
N
H
P
OEt
O
N
H
O
O
NH4OAC
12 examples, 53-96% yield
OEt
o C
70
R = Aryl, alkyl, heteroaryl
Extended author information available on the last page of the article
Vol.:(0123456789)
1 3

S. Askari et al.
Keywords Heterogeneous catalyst · Metal–organic frameworks · UiO-66-NH2 · Phosphinic acid · Hantzsch reaction
such as sulfonated porous polymeric network [39], Lewis
acid ionic liquid@Fe3O4 [40], Fe3O4@TiO2-Pr-2AB@Cu
[41], IRMOF-3 [42], PANI-hydroxyethane-1,1-diphospho-
nic acid [43], Ni@ionic liquid-based ordered mesoporous
organosilica [44], SiO2/IL(PF6)-SO3H [45], and vanadium
ion-doped TiO2 [46].
1 Introduction
Organophosphorous compounds are produced via the for-
mation of carbon–phosphor bonds [1]. Among organophos-
phors, phosphinic acids are very valuable compounds due to
their applications in medicine, agriculture, removal of heavy
metals, and catalysis [2–7]. α-Aminoalkylphosphinic acids
or bis(α-aminoalkyl)phosphinic acids are easily produced
by a reaction of amines (primary and secondary), aldehydes,
and hypophosphorous acid through methods of Kabach-
nik–Fields, Mannich, Arbuzov, and Michaelis–Becker [8].
The synthesis of aminoalkylphosphinic acid depends on the
basic strength (i.e., pH) of the amine, as it reduces the oxi-
dation of hypophosphorous acid to phosphorous acid and
eliminates the generation of by-products. The synthesis also
depends on the steric hindrance of the aldehyde, as less hin-
drance aldehyde (e.g., formaldehyde) is favorable [9]. Bis(α-
aminoalkyl)phosphinic acids, as bifunctional catalysts with
Brønsted acid (P–OH) and base (P=O) sites, are very attrac-
tive for organic syntheses [10].
Herein, we report the preparation and characterization
of UiO-66-NH–CH2CH2N(CH2PO2H2)2 as a novel porous
heterogeneous acid catalyst with pKa < 7–8 [47]. Zirco-
nium-based MOF, UiO-66-NH2, is selected as a support for
post-synthesis modifcation (PSM) [48, 49] due to its high
thermal and chemical stability [50]. UiO-66-NH2 is modi-
fed consecutively with ethylamine (pKa >10) [51], formal-
dehyde, and hypophosphorous acid. The as-prepared solid
acid catalyst is then successfully used for the synthesis of
polyhydroquinolines. The efect of various factors such as
the catalyst amount, solvent polarity, and reaction tempera-
ture are studied. The catalyst recoverability and reusability
are also investigated.
Heterogeneous catalysis are fascinating in the aspects of
the economy and environment (i.e., recyclability and reus-
ability) [11]. They are typically produced by heterogenizing
a catalytic system on an appropriate solid support such as
Fe3O4 nanoparticles (NPs), silica, activated carbon, polymer,
metal–organic frameworks (MOFs), etc. [12–15]. MOFs
generally prepare from a reaction of metal ions (as cores)
with organic bi/multi-functional ligands (as linkers) and gen-
erate three-dimensional periodical frameworks. They ofer
high surface area and large porosity [16], high thermal and
chemical stability [17], low density [18], and easy function-
alization [19]. MOFs are intrinsically showed catalytic activ-
ity via open metal sites (i.e., Lewis acid) and functionalized
organic linkers [20–22]. They are also used as support for
metal NPs and organocatalysts. Such systems have found a
broad range of applications in organic synthesis [23–26],
photocatalysis [27, 28], and electrocatalysis [29].
2 Experimental
2.1 Material and Characterization Tools
The chemicals were purchased from Merck and used without
any additional purifcation. Powder X-ray difraction (XRD)
was carried out by a Philips X-ray difractometer with a Cu
Kα radiation source (λ=1.5406 Å). Infrared spectra were
recorded with a FT-IR spectrometer, IRPrestige-21 Shi-
madzu. The morphology of the samples was studied by feld
emission scanning electron microscopy (FESEM) using a
TESCAN MIRA3 equipped with energy-dispersive spectros-
copy (EDS). Thermogravimetric analysis was carried out on
a Q600 instrument with a heating rate of 10 °C min−1 under
an argon atmosphere. The BET surface area and pore vol-
ume were measured by a Belsorp mini II porosimeter. The
organic products were identifed by 1H and 13C nuclear mag-
netic resonance (NMR) on a Bruker AVANCE (500 MHz)
spectrometer.
Multi-component reactions (MCRs), such as Biginelli
[30], Ugi [31], and Hantzsch [32], are widely used for the
synthesis of a large variety of heterocyclic compounds.
Hantzsch synthesis of polyhydroquinolines (PHQ) has
received much attention due to its biological and pharma-
ceutical applications. They can be found in the formulation
of drugs such as anti-infammatory, antitumor, painkiller,
calcium channel blockers, and bronchodilator [33, 34]. Poly-
hydroquinolines are synthesized by employing four compo-
nents (aldehyde, ethyl acetoacetate, dimedone, and ammo-
nium acetate) [35] in the presence of basic [36], acidic [37],
metallic [38], and enantioselective organic [7] catalyst. Vari-
ous catalytic systems have been developed in recent years
2.2 Post‑Modifcation of UiO‑66‑NH2
with Ethylamine (UiO‑66‑NH–CH2CH2NH2)
UiO-66-NH2 was prepared according to the procedure
described in the literature [52]. Then, the as-prepared
UiO-66-NH2 (0.5 g) was dispersed in 50 mL DMF under
ultrasonic irradiation and 2-chloroethylamine hydrochlo-
ride (0.73 mmol, 0.084 g) was added and the mixture was
stirred at 80 °C for 24 h. Then, the modifed MOF was
1 3

Heterogenized Phosphinic Acid on UiO-66-NH2: A Bifunctional Catalyst for the Synthesis…
separated, washed with DMF (3 × 10 mL) and ethanol
(3 × 10 mL), and dried at 80 °C in an oven overnight.
(1 mmol, 0.13 mL), and ammonium acetate (1.2 mmol,
0.092 g). The mixture was stirred at 70 °C for an appro-
priate time to complete the reaction and the progress of
the reaction was monitored by TLC. The catalyst was
separated by centrifugation, washed with ethanol several
times, and dried in an oven at 80 °C overnight to regener-
ate for the next run of the reaction. The organic products
were isolated from the reaction mixture by evaporation of
the solvent, purifed by recrystallization with ethanol, and
2.3 Functionalization of UiO‑66‑NH‑EtNH2
with Hypophosphorous Acid
(UiO‑66‑NH‑CH2CH2N(CH2PO2H2)2)
The procedure was adopted from the method described
by Urbanovský et al. [9]. The UiO-66-NH-CH2CH2NH2
(0.5 g) was dispersed in 50 mL MeOH under ultrasonic
irradiation (5 min), then formaldehyde (1.60 mmol,
0.058 mL) added to give the corresponding imine, and the
mixture stirred at room temperature for 24 h. The product
(UiO-66-NH-CH2CH2N=CH2) was isolated by centrifu-
gation, washed with methanol (3 × 10 mL), and dried at
60 °C overnight. After that, UiO-66-NH-CH2CH2N=CH2
was dispersed in 50 mL of CH3CN under ultrasonic
irradiation (5 min), hypophosphorous acid (1.60 mmol,
0.07 mL) added, and the mixture stirred at room tempera-
ture for 24 h. Finally, UiO-66-NH-CH2CH2N(CH2PO2H2)2
was isolated by centrifugation, washed with acetonitrile
(3 × 10 mL), and dried at 80 °C in an oven overnight.
1
identifed by measuring their melting points and H and
13C NMR spectroscopies (Figs. S1–S5). The reusability of
the catalyst was performed for the model reaction in opti-
mum conditions: using benzaldehyde (1 mmol), dimedone
(1 mmol), ethyl acetoacetate (1 mmol), and ammonium
c
b
2.4 General Procedure for the Synthesis
of Polyhydroquinolines
a
0
10
20
30
40
50
60
70
80
2θ (angle)
UiO-66-NH-CH2CH2N(CH2PO2H2)2 (0.02 g), as a hetero-
geneous catalyst, was initially dispersed in 1 mL ethanol
and then added to a mixture of benzaldehyde (1 mmol,
0.11 mL), dimedone (1 mmol, 0.14 g), ethyl acetoacetate
Fig. 1 XRD patterns of
a
UiO-66-NH2,
b
UiO-66-NH-
UiO-66-NH-
CH2CH2N(CH2PO2H2)2
(fresh),
and
c
CH2CH2N(CH2PO2H2)2 (after fve times reused)
NH2
NH
CH2O, MeOH
RT, 24 h
2-chloroethylamine, DMF
NH2
80 oC, 24 h
O
P
OH
H
NH
H3PO2, CH3CN
NH
N=CH2
N
RT, 24 h
H
P
OH
O
Scheme 1 Preparation of UiO-66-NH-CH2CH2N(CH2PO2H2)2
1 3

S. Askari et al.
acetate (1.2 mmol) as precursors, EtOH (1 mL) as a sol-
vent, with 0.02 g of the catalyst at 70 °C in 60 min.
3 Results and Discussion
3.1 Preparation and Characterization
2.5 Determination of the Number of Brønsted
of UiO‑66‑NH‑CH2CH2N(CH2PO2H2)2
Acidic Sites in UiO‑66‑NH‑CH2CH2N(CH2PO2H2)2
A heterogeneous acid catalyst of UiO-66-NH-
CH2CH2N(CH2PO2H2)2 was prepared via multi-step func-
tionalization of zirconium-based MOF with ethylamine,
formaldehyde, and hypophosphorous acid (Scheme 1). The
catalyst was characterized by diferent techniques such as
XRD, SEM/EDX, FT-IR, TGA, and BET.
To determine the number of Brønsted acidic sites a
back titration method was used. 0.1 g UiO-66-NH-
CH2CH2N(CH2PO2H2)2 was added into 10 mL NaOH solu-
tion (0.1 M) and stirred at room temperature for 24 h. The
catalyst was then separated from the solution by centrifuga-
tion, and the resulting solution was titrated with 0.1 M HCl
solution. The titration process was monitored with phenol-
phthalein as an indicator. The number of H+ was found to
be 1.85 mmol g−1.
In Fig. 1, the X-ray difraction (PXRD) of UiO-66-NH-
CH2CH2N(CH2PO2H2)2 showed an almost identical pattern
with the pattern of UiO-66-NH2, indicating well structural
preservation of UiO-66-NH2 during multi-step modifca-
tion in diferent solvents, acidic conditions (last stage), pro-
longed process, and even elevated temperature (frst stage).
The characteristic difractions of UiO-66-NH2 were found to
be well-consistent with reported data in the literature [53].
After post-modifcations, the intensity of the corresponding
refections was slightly decreased accordingly.
2.6 Adsorption of Pyridine
on UiO‑66‑NH‑CH2CH2N(CH2PO2H2)2
UiO-66-NH-CH2CH2N(CH2PO2H2)2 (0.1 g) was dispersed
in 10 mL ethanol assisted with ultrasonic irradiation and
then the mixture stirred at room temperature after the addi-
tion of pyridine (0.315 mmol, 0.025 mL). After 24 h, the
catalyst was separated by centrifugation, washed with etha-
nol (3×10 mL), and dried at 70 °C in an oven overnight. The
presence of adsorbed pyridine on the surface of the catalyst
was investigated by FTIR.
The morphology of UiO-66-NH-CH2CH2N(CH2PO2H2)2
was studied by SEM analysis (Fig. 2). The SEM image
showed particles with an irregular and pseudo-spherical
shape in a size range of 50–100 nm. The similarity in shape
and size of UiO-66-NH-CH2CH2N(CH2PO2H2)2 with
those in UiO-66-NH2 indicates the structural stability of
UiO-66-NH2 during multi-step modifcations. The modif-
cation was verifed with the existence of the correspond-
ing elements (i.e., Zr, O, C, N, and P) in the structure of
Fig. 2 SEM images of a UiO-66-NH2 and b UiO-66-NH-CH2CH2N(CH2PO2H2)2
1 3

Heterogenized Phosphinic Acid on UiO-66-NH2: A Bifunctional Catalyst for the Synthesis…
Fig. 3 EDS spectrum and elemental mapping of UiO-66-NH-CH2CH2N(CH2PO2H2)2
1 3

S. Askari et al.
Fig. 4 FTIR spectra of a
UiO-66-NH2, b UiO-66-NH-
CH2CH2NH2, c UiO-66-NH-
CH2CH2-N=CH2, d UiO-66-
NH-CH2CH2N(CH2PO2H2)2
(fresh), and e UiO-66-NH-
CH2CH2N(CH2PO2H2)2 (after
fve times reused)
e
d
P–O
P=O
P–OH
c
b
a
C–H
2800
N–H
C=O
Zr–O
4000
3600
3200
2400
2000
1600
1200
800
400
Wavenumber (cm-1)
Fig. 5 TGA thermograms of
UiO-66-NH2 and UiO-66-NH-
CH2CH2N(CH2PO2H2)2
100
UiO-66-NH
UiO-66-NH-CH CH N(CH PO H )
90
80
70
60
50
40
30
0
100
200
300
400
500
600
Temperature (°C)
UiO-66-NH-CH2CH2N(CH2PO2H2)2 (Fig. 3). In addition,
the elemental mapping demonstrated a homogeneous dis-
tribution of the elements in the modifed MOF particles.
The diferent steps of modifcation of UiO-66-NH2 were
investigated by FTIR (Fig. 4). The characteristic peaks of
UiO-66-NH2 can be observed at ~ 3440 and ~ 1620 cm−1
assigned to the stretching and bending vibrations of
N–H, respectively [54], while the peak at ~ 1570 cm−1
corresponded to the carboxylate groups of the linker inter-
acted with Zr4+ of the node [55]. The corresponding bands
of Zr–O were also found at ~ 660, ~ 520, and ~ 475 cm−1.
After ethylamine grafting, C–H aliphatic peaks were
observed at 2920 and 2850 cm−1, besides a slight peak shift
towards~3410 cm−1 for N–H stretching (Fig. 4b). The cor-
responding stretching and bending vibrations of the –NH2
group were disappeared after the addition of formaldehyde
1 3

Heterogenized Phosphinic Acid on UiO-66-NH2: A Bifunctional Catalyst for the Synthesis…
Fig. 6 N2 adsorption–desorp-
tion isotherms and pore size
distributions of UiO-66-NH2
and UiO-66-NH-CH2CH2N(CH
2PO2H2)2
400
300
200
100
0
ADS-UiO-66-NH
DES-UiO-66-NH
ADS-UiO-66-NH-CH CH N(CH PO H )
DES-UiO-66-NH-CH CH N(CH PO H )
0
0.2
0.4
0.6
0.8
1
Relative pressure (P/P°)
0.04
0.03
0.02
0.01
0
UiO-66-NH
UiO-66-NH-CH CH N(CH PO H )
0
20
40
60
80
100
Pore width (nm)
and the formation of the imine (CH2=N) group (Fig. 4c). For
UiO-66-NH-CH2CH2N(CH2PO2H2)2, the stretching bands
of P–O (~1070 and~1050 cm−1), P=O (~1135 cm−1), and
P–OH (~760 cm−1) were observed to confrm the formation
of phosphinic acid on the surface of the MOF (Fig. 4d) [56].
The number of Brønsted acid sites was determined by titra-
tion and found to be 1.85 H+ per gram.
Table 1 BET surface area and porosity data for UiO-66-NH2 and
UiO-66-NH-CH2CH2N(CH2PO2H2)2
Materials
Specifc sur-
Total pore
volume
Mean pore
size (nm)c
face area
(m2 g−1 a
)
(cm3 g−1 b
)
UiO-66-NH2
1056
0.54
0.39
2.05
2.17
UiO-66-NH-CH2CH2N 725
The thermogravimetric analysis (TGA) was employed
to evaluate the thermal stability and estimate the quan-
tity of the loaded organic species in the UiO-66-NH-
CH2CH2N(CH2PO2H2)2. The thermogram of the modifed
MOF showed an earlier weight loss phenomenon at a tem-
perature below 100 °C compared to that in UiO-66-NH2.
(CH2PO2H2)2
aSBET
bTotal pore volume determined at P/P0 =0.99
cMean pore diameter determined using the BJH method.
1 3

S. Askari et al.
The weight loss of ~ 15% was observed corresponding to
the removal of the physically adsorbed solvent and moisture
from the highly hydrophilic nature of the modifed MOF
(Fig. 5). The second weight loss of~14%, observed in the
range of 100–300 °C, which might be related to the partial
degradation of organic species in the modifed MOF. For
UiO-66-NH2, the removal of coordinated DMF happened
at the second weight loss at the temperature>180 °C [57].
At temperature>300 °C, the third weight loss of~37% was
related to the entire decomposition of organic components
in the modifed MOF and the degradation of the MOF struc-
ture. Overall, the modifed MOF exhibited less thermal sta-
bility, compared to the parent MOF, due to the presence of
organic species.
3.2 UiO‑66‑NH‑CH2CH2N(CH2PO2H2)2
as a Heterogeneous Catalyst
The catalytic activity of the modifed MOF was studied for the
synthesis of polyhydroquinolines. A four-component Hantzsch
reaction between benzaldehyde, dimedone, ethyl acetoacetate,
and ammonium acetate was selected as a model reaction. The
efect of solvent type, temperature, and catalyst amount were
investigated to fnd optimum conditions (Table 2). Among dif-
ferent types of solvent (entries 2–6), EtOH gave the highest
product yield. The polar solvents exhibited better efciency
compared to the non-polar solvents. In the absence of sol-
vent, a yield of 55% was obtained. The room and moderate
temperatures were applied for the reaction and the best result
was found for the temperature of 70 °C (entries 6–8). The
amount of catalyst was investigated (entries 6 and 9–11) and
the results showed that 0.02 g of the catalyst was sufcient
to aford the highest yield. Therefore, the optimal conditions
(catalyst amount: 0.02 g, solvent: ethanol, temperature: 70 °C)
were employed for further studies.
The surface area and porosity of the modifed MOF were
studied. The N2 adsorption–desorption isotherm and poros-
ity data of UiO-66-NH-CH2CH2N(CH2PO2H2)2 are shown
in Fig. 6 and Table 1, respectively. The isotherms exhibited
type I defned for microporous materials [58]. As expected,
the BET surface area (725 m2 g−1) and the total pore volume
(0.39 cm3 g−1) were decreased after the post-modifcation of
UiO-66-NH2.
Diferent types of aromatic, aliphatic, and heterocy-
clic aldehydes were used to evaluate the capability of
Table 2 Optimization of the reaction conditionsa
O
O
O
O
OEt
CHO
O
OEt
N
H
O
NH4OAC
Entry
Solvent
Catalyst amount (g)
Temperature (°C)
Yield (%)b
1
2
3
4
5
6
7
8
Solvent-free
CH2Cl2
CH3CN
H2O
EtOH: H2O (1:1)
EtOH
EtOH
EtOH
EtOH
EtOH
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.02
0.06
0.08
0.01
70
70
70
70
70
70
50
25
70
70
70
55
35
65
69
70
95
83
43
95
95
68
9
10
11
EtOH
aReaction conditions: benzaldehyde (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate (1.2 mmol), solvent (1 mL),
catalyst, 60 min
bIsolated yield
1 3

Heterogenized Phosphinic Acid on UiO-66-NH2: A Bifunctional Catalyst for the Synthesis…
Table 3 Synthesis of
Entry
Aldehyde
Time (min)
Yield (%)b
m.p. (°C) found
m.p. (°C)
polyhydroquinoline
Lit. [Refs.]
derivatives using UiO-66-NH-
CH2CH2N(CH2PO2H2)2 as a
heterogeneous catalyst.a
1
2
3
4
5
6
7
8
C6H5CHO
60
55
65
55
65
65
55
55
65
65
65
70
95
96
89
90
90
89
91
87
82
85
89
53
[201–204]
[255–257]
[258–260]
[233–235]
[241–245]
[242–245]
[242–244]
[174–176]
[66–68]
202–204 [59]
254–256 [59]
261–262 [59]
232–234 [32]
232–234 [32]
244–245 [59]
241–243 [59]
176–178 [32]
66–67 [60]
4-OMe-C6H4CHO
4-Me-C6H4CHO
4-OH-C6H4CHO
4-Cl-C6H4CHO
2,4-Cl2-C6H3CHO
4-NO2-C6H4CHO
3-NO2-C6H4CHO
C5H4N-3-CHO
C4H3S-2-CHO
C10H7-1-CHO
9
10
11
12
[239–241]
[231–233]
[145–147]
238–240 [59]
232–233 [61]
147–148 [60]
CH3(CH2)2CHO
aReaction conditions: aldehyde (1 mmol), dimedone (1 mmol), ethyl acetoacetate (1 mmol), ammonium
acetate (1.2 mmol), EtOH (1 mL), catalyst (0.02 g, 0.037 mmol H+), 70 °C.
bIsolated yield
Table 4 Catalytic activity of the diferent components of the catalyst.a
Entry Catalyst
Time (min) Yield (%)b
acid sites. Therefore, the role of Brønsted acid sites in
the reaction is more pronounced, compared to the Lewis
acid sites, in UiO-66-NH-CH2CH2N(CH2PO2H2)2. The
pyridine adsorption test was utilized to explore all avail-
able acid sites on the catalyst structure. The FTIR spec-
tra, in Fig. S6, exhibited a slight peak shift to the higher
frequency (769 cm−1, compared to 767 cm−1 in the bare
catalyst) for the vibration of P–OH (Brønsted acid) after
adsorption of pyridine and its interaction with the Brøn-
sted acid sites. Such peak shifts to the higher frequency,
661 and 478 cm−1, were also observed for the vibration
of Zr–O (Lewis acid sites) compared to those (659 and
476 cm−1) in the bare catalyst. Therefore, a synergistic
efect is expected to happen by the contribution of the
support (i.e., Lewis acid sites) on the catalytic activity of
phosphinic acid (i.e., Brønsted acid sites).
1
2
3
UiO-66-NH2
Hypophosphorous acid (H3PO2)
60
60
60
35
78
95
UiO-66-NH-CH2CH2N(CH2P
O2H2)2
aReaction conditions: benzaldehyde (1 mmol), dimedone (1 mmol),
ethyl acetoacetate (1 mmol), ammonium acetate (1.2 mmol), EtOH
(1 mL), catalyst (0.02 g), 70 °C.
bIsolated yield
UiO-66-NH-CH2CH2N(CH2PO2H2)2 in catalyzing the
Hantzsch reaction (Table 3). The aryl aldehydes bearing
electron-withdrawing and electron-donating groups were
converted to the corresponding polyhydroquinolines in
good to excellent yields (entries 2–8). Heteroaromatic
aldehydes such as pyridine-3-carbaldehyde and thiophene-
2-carbaldehyde (entries 9 and 10) showed lower efciency
compared to the aryl aldehydes. Furthermore, the aliphatic
aldehyde (i.e., butanal) exhibited a moderate yield in the
reaction (entry 12).
A plausible mechanism for the four-component
synthesis of polyhydroquinolines using UiO-66-NH-
CH2CH2N(CH2PO2H2)2 is shown in Scheme 2. Although
both Brønsted and Lewis acidic sites are available for the
catalyst, the more pronounced active site (Brønsted acid)
was considered in the drawing of the mechanism. Initially,
the hydroxyl (acid site) and the oxygen lone pair (base
site) of the phosphinic group [10] activate benzaldehyde
and dimedone, respectively. The enolate form of dimedone
adds, via a nucleophilic attack, to the carbonyl group of
the activated aldehyde and then dehydration occurs via the
Knoevenagel condensation (intermediate I). On the other
hand, ethyl acetoacetate reacts with ammonium acetate to
produce enamine (intermediate II) in the presence of the
catalyst. A Michael addition reaction of the intermediate
II with the intermediate I generates the intermediate III,
The performance of the supported phosphinic acid as
a heterogeneous catalyst was compared with phosphinic
acid in a homogeneous form (Table 4). The supported acid
exhibited a higher yield, which could be related to a syn-
ergistic efect of the support (i.e., UiO-66-NH2) on the
catalytic reaction. Interestingly, the support showed solely
a catalytic activity on the synthesis of polyhydroquinoline.
It is known that the open metal sites in the nodes of MOFs
act as Lewis acid [21]. Since the post-modifcation limits
the accessibility of open metal sites by blocking the pores,
a limited performance is expected to observe for Lewis
1 3

S. Askari et al.
O-
H
O
O
O
H
O
O
H
H
O
H
P
O
H
NH4OAC
-HOAC
O
O
H
O
O
H
H
P
H
O
H
O
H
O
NH3
P
OH
P
O
O
H
O
H
-H2O
OEt
H
N
O
O
N
O
NH3
-H2O
H
O
OEt
OEt
H
H
I
HO
P
H
O
O
O
H
O
O
N
P
O
H
H
H
O
O
H
H
EtO
III
P
O
O
EtO
H
N
H
O
O
II
IV
H
O
O
H
P
O
H
O
H
H
EtO
OH
P
OH
N
H
O
N
P
O
O
OEt
H
H
O
O
O
H
H
P
O
P
OH
H
Scheme 2 Plausible mechanism for the synthesis of polyhydroquinolines
followed by an intramolecular cyclization to intermedi-
ate IV. The product is fnally formed by a dehydration
reaction.
3.3 Reusability of the Catalyst
The recyclability and reusability of the catalyst were inves-
tigated for the model reaction. The catalyst was separated
from the reaction medium by centrifugation and reacti-
vated by washing (with ethanol) and drying (at 70 °C over-
night). The recovered catalyst was then reused fve times
without substantial loss of the catalytic activity (Fig. 7).
The slight reduction in the reactivity of the catalyst might
be related to the occupation of the open metal sites and
the blockage of the MOF pores by trapped reactants/prod-
uct/solvent. These phenomena are generally observed in
MOFs particularly in catalysis reaction [22]. Gong et al.
reported that MOF-based Brønsted acids sufer catalytic
deactivation in polar solvents [63]. Our study showed
that the number of Brønsted acid sites, H+, in the cata-
lyst was reduced to 1.73 mmol g−1 (from 1.85 mmol g−1
for the fresh catalyst) after fve times recycling/reusing.
Therefore, a combination of occupied Lewis acid sites and
100
95
95
90
85
80
75
70
93
90
89
87
85
1
2
3
4
5
6
Run No
Fig. 7 Reusability of the catalyst for the model reaction under identi-
cal conditions
1 3

Heterogenized Phosphinic Acid on UiO-66-NH2: A Bifunctional Catalyst for the Synthesis…
Table 5 The comparative study
Entry Catalyst
Conditions
Time (min) Yield (%) [Refs.]
on the catalytic activity of
diferent catalytic systems
1
2
3
4
5
6
7
8
ED/MIL‐101(Cr) (0.5 g, 4 mol%)
[Fe3O4@SiO2@(CH2)3Py]HSO4− (0.025 g)
Pd‐SBTU@Fe3O4 (0.01 g)
Fe3O4@MCM-41@Cu-P2C (0.02 g)
CoFe2O4@Pr (0.04 g)
SBA-15@Glycine-Cu (0.08 g)
IRMOF-3 (0.04 g, 5 mol%)
UiO-66-NH-CH2CH2N(CH2PO2H2)2 (0.02 g) EtOH, 70 °C
EtOH, 80 °C
EtOH, refux
PEG, 80 °C
PEG, 80 °C
EtOH, refux
EtOH, 80 °C
120
90
140
180
90
98 [63]
98 [64]
95 [65]
95 [66]
97 [67]
150
92 [68]
92 [42]
Solvent-free, 60 °C 180
60
95 [this work]
decreased Brønsted acid sites brought about a reduction in
the catalytic activity.
UiO-66-NH-CH2CH2N(CH2PO2H2)2. The structure of UiO-
66-NH2 was preserved during three-step modifcations. The
morphology of the modifed MOF was similar to that of
the parent MOF with well-distribution of the correspond-
ing elements in its structure. The catalyst was employed for
the synthesis of polyhydroquinoline derivatives via the four-
component Hantzsch reaction. The catalyst exhibited high
performance in the synthesis using diferent types of alde-
hydes (aromatic, heterocyclic, and aliphatic). Reasonable-to-
high yields and shorter reaction times were also observed. In
fact, Brønsted acid and Lewis base sites in phosphinic acid
and Lewis acid sites in the support were synergistically cata-
lyzed the Hantzsch reaction. The catalyst was easily recy-
cled and efciently reused without signifcant reduction in its
activity. We believe that our catalyst has sufcient durability
and robustness, which are important factors for the develop-
ment of a new catalytic system for acid-catalyzed syntheses.
It is expected that the MOF/phosphinic acid hybrid system
receive the attention of chemical industries.
The stability of the catalyst was also examined by
PXRD, FTIR, SEM, and EDS/elemental mapping after
fve times reusing. The comparison between the results for
the fresh and the reused catalysts revealed the structural
preservation of the catalyst. The crystallinity (Fig. 1c) and
morphology (Fig. S7) of the reused catalyst were retained
after several recovering and reusing. The main func-
tional groups on the reused catalyst were also unchanged
(Fig. 4e). The elemental analysis/distribution of the cata-
lyst showed no signifcant changes after fve-run of reus-
ing (Fig. S7). The leaching test was performed to evalu-
ate the catalyst durability using the model reaction under
optimized conditions (Fig S8). The reaction was stopped
after 15 min and the catalyst separated from the reaction
medium, then the reaction continued in the absence of the
catalyst for 60 min. A reaction yield of 27% was found. In
another testing, the reaction proceeded for 30 min, then
the catalyst removed from the medium, and the reaction
let continue for 60 min in the absence of the catalyst. A
yield of 55% was obtained. We believe that the leaching
was negligible during the reaction, and after the removal
of the catalyst, the reaction was not able to proceed further
to a higher yield.
Supplementary Information The online version contains supplemen-
tary material available at https://doi.org/10.1007/s10562-021-03734-1.
Acknowledgements The authors gratefully acknowledge Razi Univer-
sity for fnancial support.
The efficiency of our catalyst was compared with
the reported catalytic systems for the synthesis of ethyl
2,7,7-trimethyl-5-oxo-4-phenyl-1,4,5,6,7,8-hexahy-
droquinoline-3-carboxylate (Table 5). UiO-66-NH-
CH2CH2N(CH2PO2H2)2 showed a comparable catalytic
performance by using a low catalyst amount, shorter reac-
tion time, and good to excellent yields.
Declarations
Conflict of interest There are no conficts to declare.
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1 3

Heterogenized Phosphinic Acid on UiO-66-NH2: A Bifunctional Catalyst for the Synthesis…
Authors and Afliations
Saeed Askari1 · Mohammad Mehdi Khodaei1,2 · Mohammad Jafarzadeh1,2
2
* Mohammad Mehdi Khodaei
Nanoscience & Nanotechnology Research Center (NNRC),
Razi University, 67149-67346 Kermanshah, Iran
mmkhoda@razi.ac.ir
1
Department of Organic Chemistry, Razi University,
67149-67346 Kermanshah, Iran
1 3