Synthesis of new α-aminophosphonates using nanoscale nickel-based metal–organic framework as a heterogeneous catalyst and their antibacterial activity

Article abstract of DOI:10.1002/aoc.5317

An elegant approach was presented for the synthesis of novel α-aminophosphonates: a three-component one-pot condensation of 3-(trifluoromethyl)aniline, substituted aromatic aldehydes, and diethyl phosphite using a nickel-based metal–organic framework (Ni-

Full text of DOI:10.1002/aoc.5317

Received: 16 July 2019
DOI: 10.1002/aoc.5317
Revised: 21 September 2019
Accepted: 8 October 2019
F U L L P A P E R
Synthesis of new α-aminophosphonates using nanoscale
nickel-based metal–organic framework as a heterogeneous
catalyst and their antibacterial activity
Sarika A. Rasal1 | Pratik P. Dhavan2 | Bhaskar L. Jadhav2
Navinchandra G. Shimpi1
|
1Laboratory for Material Science,
Abstract
Department of Chemistry, University of
Mumbai, Santacruz (E), Mumbai, 400098,,
India
2Department of Life Sciences, University
of Mumbai, Santacruz (E), Mumbai,
400098,, India
An elegant approach was presented for the synthesis of novel α-aminophosp-
honates: a three-component one-pot condensation of 3-(trifluoromethyl)ani-
line, substituted aromatic aldehydes, and diethyl phosphite using a nickel-
based metal–organic framework (Ni-MOF). The Ni-MOF was synthesized
using 4,40-biphenyldicarboxylic acid and further characterized using various
techniques such as X-ray diffraction, Fourier-transform infrared, thermogra-
vimetry/differential thermal analysis, Brunauer–Emmett–Teller, and field-
emission scanning electron microscopy analyses. Ni-MOF seems to be an eco-
friendly, an easily recyclable, and heterogeneous catalyst up to the eighth run
with minimal reduction in its catalytic activity. The synthesized
α-aminophosphonates were also investigated for antibacterial and antioxidant
activities. In few cases, compounds 4a–4x show similar as well as higher
antibacterial activity. Among the synthesized α-aminophosphonates, 4a–4x
had more potent antibacterial activity against pathogenic bacteria while com-
pounds 4h, 4m, 4n, 4q, 4u, 4v, and 4w exhibited significant antioxidant
activity.
Correspondence
Navinchandra G. Shimpi, Laboratory for
Material Science, Department of
Chemistry, University of Mumbai,
Santacruz (E), Mumbai 400098, India.
Email: navin_shimpi@rediffmail.com
Funding information
DST-PURSE
K E Y W O R D S
antibacterial activity, antioxidant activity, catalysis, metal–organic framework,
α-Aminophosphonates
1 | INTRODUCTION
adsorption, biomedicine, molecular-based magnetism,
drug delivery, and sensors, due to their characteristic
Metal–organic frameworks (MOFs) are the combination
of organic and inorganic chemistry whose structure is
defined by a three-dimensional arrangement of metal
ions or clusters coordinated to bipodal or multipodal
organic ligands.[1–3] Mainly, varieties of metal such as
alkaline, alkaline earth, transition metals, and rare
earth metals have been used in the preparation of
MOFs.[4] MOFs have attracted great attention in vari-
ous applications, such as gas storage/separation/
properties (porosity, crystallinity, specific surface area,
low density, and relatively strong metal–ligand coordi-
nation bond).[5–10]
The most significant application of MOFs is in hetero-
geneous catalysis.[11] The catalytic activity of MOFs
depends on active sites such as metal centers and organic
linkers. The area of MOFs has become one of the fastest
growing fields in catalysis because of their structural and
functional tunability. The activity of MOFs is focused on
Appl Organometal Chem. 2019;e5317.
wileyonlinelibrary.com/journal/aoc
© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.5317

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RASAL ET AL.
several features such as the use of commercial MOFs as a
catalyst in comparison with other porous solids or their
activity to promote organic transformation reactions (car-
bon–carbon and carbon-heteroatom bond forma-
tion).[12,13] The increase in the length of organic linkers
increases pore dimension as well as surface area, which
leads to smaller size[14] and eventually to the formation
of nanoscale MOFs. These materials provide the features
similar to or even more than nanomaterials.[15]
α-aminophosphonates were screened in vitro for
antibacterial (resazurin microtiter assay [REMA]
method) and antioxidant (2,2-diphenyl-1-picrylhydrazyl
[DPPH] method) activities. The results obtained revealed
that α-aminophosphonates (4a–4x) have good to excellent
antibacterial and antioxidant activities.
2 | EXPERIMENTAL
The Kabachnik–Fields reaction is a versatile reaction
for the formation of carbon–phosphorus bonds.[16,17]
Many natural and synthetic aminophosphonic acid and
ester derivatives display a wide range of biological prop-
erties such as antimicrobial,[18] antioxidant,[19] anti-
inflammatory,[20] antitumor,[21] and insecticidal activi-
ties[22] and also act as enzyme inhibitors.[23] Owing to
their biological importance, different routes have been
developed for the synthesis of aminophosphonate using
various starting materials.[24] Recently, our research
group has synthesized novel α-aminophosphonates using
different substituted aldehydes and amines.[25] The inves-
tigation of new α-aminophosphonates thus remains an
attractive area of all synthetic organic chemists. This has
led to a rapidly expanding interest in exploring their
properties and uses.
The literature describes very few studies on nickel-
based MOF (Ni-MOF) as catalysts for organic transforma-
tion reactions. Kim and co-workers prepared nickel
nanoparticles embedded in MOFs for hydrogenation,[26]
while Chou and co-workers used MOF-5-supported
nickel nanoparticles as a catalyst for hydrogenation of
crotonaldehyde.[27] Jiang and co-workers utilized nickel
(salphen)-based MOF for CO2 absorption and in situ
asymmetric fixation.[28] Canivet and co-workers
anchored a nickel complex into a mesoporous MOF to
generate an active and reusable catalyst, which was used
in the liquid-phase ethylene dimerization to selectively
form 1-butene.[29] Truong and co-workers synthesized
Ni2(BDC)2(DABCO) as a catalyst for oxidative coupling
of alkynes and arylboronic acids.[30] Zuo and co-workers
used N-doped mesoporous carbon–supported Ni
nanoparticles for the reduction of nitroarenes.[31] More-
over, Aryanejad and co-workers investigated novel Ni-
MOF as a catalyst for benzyl alcohol oxidation and cas-
cade reaction.[15]
2.1 | Materials and characterization
All reagents and starting materials were used as
received without further purification (Sigma-Aldrich
and Merck, India). The crystalline nature of Ni-MOF
was analyzed using powder X-ray diffractometer
(Maxima 7000 S; Shimadzu, USA) using Cu-Kα
(λ = 1.5418 Å and 1.6-kW X-ray tube with an applied
voltage of 40 kV and current values of 40 mA) radia-
tion with 2θ range from 5ꢀ to 70ꢀ at a scanning speed
of 5ꢀ min−1. Thermogravimetric analysis was per-
ꢀ
ꢀ
formed from 30 to 800 C at a heating rate 10 C/min
under an inert atmosphere (METTLER TOLEDO
STARe System, India). Brunauer–Emmett–Teller (BET)
specific surface area and pore dimension were calcu-
lated by performing N2 adsorption–desorption measure-
ments at 77 K. Surface morphology was studied using
field-emission scanning electron microscopy (FESEM;
Hitachi S-4800, Japan). Ni-MOF was prepared under
ultrasonic irradiation, which was achieved using a
multiwave ultrasonic cell crusher (SJIA-250w equipped
with a converter/transducer and titanium oscillator
horn). Thin-layer chromatography was performed using
Merck silica gel 60 F254 plates and components were
visualized under UV light (254 nm). Isolated products
were confirmed using Fourier transform infrared
(FTIR) spectroscopy (Perkin Elmer, Frontier equip-
ment) under attenuated total reflectance. 1H nuclear
magnetic resonance (NMR; 300 Hz) and 13C NMR
(75 Hz) were recorded on an NMR spectrometer
(Bruker ADVANCE II) using tetramethylsilane as an
internal standard and a gas chromatography (GC)–
mass spectrometry (MS) spectrometer (QP-2010, Rtx-17,
30 m × 0.25 mm ID, film thickness df = 0.25 μm, col-
umn flow 2 mL/min, 80–240 ꢀC at 10 ꢀC/min rise).
Elemental analysis was performed on a CHNS–O ana-
lyzer (EA300, EuroVector, Italy). The in vitro
antibacterial activity of all the synthesized compounds
was investigated using the REMA plate method to
obtain minimum inhibitory concentration (MIC) in
comparison with chloramphenicol as a standard drug.
The antioxidant activity was verified by the DPPH
scavenging method with ascorbic acid as a standard.
In continuation of our study toward the synthesis of
novel α-aminophosphonates, we herein present a simple
and expeditious synthesis of α-aminophosphonates using
an Ni-MOF as a heterogeneous catalyst under solvent-
free conditions. To our knowledge, there are no reports
on the synthesis of α-aminophosphonate using
3-(trifluoromethyl)aniline as amine in the presence of Ni-
MOF
as
a
catalyst.
A
series
of
novel

SYNTHESIS OF NEW α-AMINOPHOSPHONATES USING NANOSCALE NI-MOF
3 of 14
2.2 | General procedure for preparation
of Ni-MOF
subtilis [ATCC 6633]) and Gram-negative bacteria (Sal-
monella typhi [ATCC 23564], Escherichia coli [ATCC
25922]) by the REMA.[33] The bacterial suspension was
prepared in nutrient broth from test organisms, sub-
cultured on nutrient agar, and incubated at 37 ꢀC for
16 hr. All compounds were dissolved in dimethyl sulf-
oxide (DMSO) and further diluted with water to pre-
pare the working solution of 1000 μg/mL
concentration. Twofold serial dilutions were prepared
using a multichannel pipette such that each well has
50 μL of the test material in a series with descending
concentrations. Chloramphenicol was used as a posi-
tive control (standard drug) and DMSO as a negative
control. The microtiter platesꢀ were then sealed with
parafilm and incubated at 37 C for 24 hr. After incu-
bation, resazurin (50 μL, 0.2 mg/mL dissolved in steril-
ized distilled water) was added to each well and plates
Ni-MOF was synthesized according to a previously
reported method but with certain modifications.[32]
Nickel(II) chloride and 4,40-biphenyldicarboxylic acid
(BPDC) were used to coordinate with nickel ions in
order to form Ni-MOFs. For this purpose, initially, the
nickel(II) chloride solution (3.72 mmol) was prepared
in 100 mL deionized water (DW) and the BPDC solu-
tion (4.75 mmol) was prepared in 100 mL DW. The
pH of the organic linker solution was adjusted to 7 by
dropwise addition of 1 M NaOH solution. Nickel chlo-
ride solution was then added dropwise into the organic
linker solution under controlled ultrasound conditions
for 3 hr. The obtained green precipitate was filtered
and washed with DW in excess and further three
times using ethanol. The precipitate was dried in a hot
ꢀ
were incubated again at 37 C for 30 min. The change
ꢀ
air oven at 100 C for 24 hr.
in color from purple to pink was assessed visually. The
lowest concentration at which color change occurred
was taken as the MIC value.
2.3 | General procedure for the synthesis
of α-aminophosphonates
2.5 | Protocol for antioxidant activity
A mixture of aldehyde (1) (1 mmol), 3-(trifluoromethyl)
aniline (2) (1 mmol), diethyl phosphite (3) (1.2 mmol),
and catalyst (10 mg) were added into a 50-mL round-
bottomed flask under controlled stirring at room temper-
ature. The progress of the reaction path was monitored
by thin-layer chromatography. After completion of the
reaction, ethyl acetate was added to the reaction mixture
and the catalyst was removed by centrifugation. The sep-
arated catalyst was washed using ethanol and dried in an
The DPPH radical scavenging activity assay is one of the
standard methods used for evaluation of antioxidant
activity of compounds.[34–36] The synthesized compounds
(4a–4x) were tested for antioxidant activity by observing
their interaction with the stable free radical DPPH[37,38]
using the ascorbic acid as standard. In the following
assay, 0.1 mL of 15, 30, 60, 120, and 240 μg/mL of each
test compound, 0.8 mL of DPPH, and 0.1 mL of methanol
were added into a test tube. The absorbance of each solu-
tion was determined at 517 nm using a spectrophotome-
ter after incubation at 37 ꢀC for 30 min. Similarly,
absorbance was recorded for control (i.e. methanol and
DPPH). The DPPH scavenging ability was calculated
using following equation:
ꢀ
oven at 80 C for 24 hr. The organic layer was washed
using excess of brine and dried over anhydrous sodium
sulphate. Finally, the organic layer was concentrated and
the crude product was crystallized to obtain pure
α-aminophosphonate (Scheme 1).
Ac−As
2.4 | Protocol for antibacterial activity
DPPH scavenging ability ð%Þ =
× 100 ð1Þ
Ac
The antibacterial activity of synthesized compounds
(4a–4x) was screened against two Gram-positive bacte-
ria (Staphylococcus aureus [ATCC 25923], Bacillus
where Ac is absorbance of control; and As is absorbance
of sample.
SCHEME 1 Synthesis of α-aminophosphonate.
Ni-MOF, nickel-based metal–organic framework;
RT, room temperature

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RASAL ET AL.
3 | RESULTS AND DISCUSSION
3.1 | Characterization of Ni-MOF
The X-ray diffraction (XRD) pattern of Ni-MOF was com-
pared with organic linker to evaluate the formation of
Ni-MOF (Figure 1). The appearance of new diffraction
peaks of Ni-MOF at 5.6, 12.9, 18.6, 20.5, and 25.7ꢀ in
comparison with the organic linker (BPDC) can be
observed. The XRD pattern of Ni-MOF signifies its highly
crystalline nature. The Debye–Scherrer formula was used
to calculate the average crystallite size, which was found
to be approximately 93 nm.
Figure 2 shows FTIR spectra of Ni-MOF and BPDC.
A significant spectral shift of the carboxylate group of Ni-
MOF and BPDC confirms the coordination of ligand to
metal. In Ni-MOF, the band at 3300 cm−1 is assigned to
the stretching vibration of coordinated water molecules
and peaks at 1598, 1494, and 1430 cm−1 are attributed to
the C=C stretching mode, which confirms the presence
of the aromatic ring. There are two strong bands at 1569
and 1393 cm−1, which are assigned to the asymmetric
and symmetric vibrations of the carboxylate groups,
respectively. Besides, Ni-MOF shows two intense bands
at 682 and 769 cm−1, which indicate the C–H antiplane
bending mode of the aromatic ring. The carboxylate
group coordinates with the metal center through the bid-
entate mode, which is confirmed by the difference
between the asymmetric and symmetric vibration
bands (Δν).
FIGURE 2 Fourier transform infrared spectra of nickel-based
metal–organic framework (Ni-MOF) and 4,40-biphenyldicarboxylic
acid (BPDC)
rate 10 ꢀC/min under an inert atmosphere for the investi-
gation of thermal stability of Ni-MOF (Figure 3). The
recorded curve showed two separate weight loss steps: a
first weight loss (16.58%) from 30 to 250 ꢀC, which can be
ascribed to the loss of adsorbed and the trapped moisture
inside the framework. Another weight loss (41.69%) at
ꢀ
400 to 600 C which is due to the decomposition of the
The thermogravimetry/differential thꢀermal analysis
organic linker.
(TG-DTA) was performed from 30 to 800 C at a heating
The surface area and pore dimensions of Ni-MOF
were evaluated by standard nitrogen adsorption–
desorption measurements carried out at 77 K. Figure 4
FIGURE 1 X-ray diffraction of nickel-based metal–organic
framework (Ni-MOF) and 4,40-biphenyldicarboxylic acid (BPDC)
FIGURE 3 Thermogravimetry/differential thermal analysis
spectra of nickel-based metal–organic framework

SYNTHESIS OF NEW α-AMINOPHOSPHONATES USING NANOSCALE NI-MOF
5 of 14
3.2 | Catalytic performance of Ni-MOF
for the synthesis of α-aminophosphonates
Initially, the catalytic activity was evaluated with the cou-
pling reaction of benzaldehyde, 3-(trifluoromethyl)ani-
line, and diethyl phosphite as a model reaction under a
solvent-free condition to afford α-aminophosphonate.
The performance of Ni-MOF as a catalyst in organic reac-
tions mainly depends on the availability of catalytic sites,
which is then governed by the choice of organic linkers
and solvent/substrate polarity. Different solvents such as
water, ethanol, acetonitrile, dichloromethane, and tolu-
ene
were
screened
for
the
synthesis
of
α-aminophosphonate and their comparison with the
solvent-free condition is presented in Table 1 (Entries
1–6). The solvent-free condition gave excellent yield
(95%) compared with other solvents (Table 1, Entry 6). In
the absence of catalyst, the yield of the desired product
was only 39%, which proved that the presence of catalyst
was necessary for the reaction to complete (Table 1,
Entry 7). The effect of catalyst loading on reaction rate
was evaluated by varying the amount of catalyst from
5, 10, 20, and 30 mg while keeping other parameters con-
stant (Table 1, Entries 8–10). Hence, 10 mg of catalyst
was enough to afford 95% of α-aminophosphonate
(Table 1, Entry 6). Furthermore, the reaction was ana-
lyzed at different periods (Table 1, Entries 11–13), with
the reaction quenched after 10 min, resulting in 75% yield
which increased to 96% in 40 min.
To highlight the advantages of the Ni-MOF catalyst,
the catalytic activity of the Ni-MOF was compared with
other Ni-based MOFs including Ni-BDC Ni-BTC, and Ni-
NDC and salts such as NiCl2, Ni(NO3)2, and Ni(OAc)2
(Table 2). Interestingly, it was observed that Ni-MOF
with the organic ligand BPDC could achieve 95% conver-
sion after 30 min due to high surface area and large pore
FIGURE 4 Nitrogen adsorption–desorption isotherms of
nickel-based metal–organic framework
shows the nitrogen adsorption–desorption isotherm of
Ni-MOF. Ni-MOF presents a type IV isotherm which is
characteristic of mesoporous materials.[39] The BET sur-
face area was found to be 353 m2 g−1 and the total pore
volume of Ni-MOF was 2.902 cm3 g−1. This high surface
area and large pore dimensions of Ni-MOF can improve
its catalytic performance.
We next performed a morphology study to under-
stand the shape and size of synthesized Ni-MOF. A
nanoplatelet-like morphology was noted , which is
shown in Figure 5a. According to BET analysis results,
Ni-MOF has an average diameter of 40–50 nm and larger
pore dimensions. The energy-dispersive X-ray spectrum
of Ni-MOF is depicted in Figure 5b, which shows the
presence of only Ni, C, and O, thus confirming that Ni-
MOF is free from impurities.
FIGURE 5 (a) Field-emission scanning electron microscopy and (b) energy-dispersive X-ray of nickel-based metal–organic framework

6 of 14
RASAL ET AL.
TABLE 1 Effect of parameter on synthesis of α-aminophosphonatea
Entry
Catalyst amount (mg)
Solvent
Time (min)
Yield (%)b
1
10
10
10
10
10
10
–
Water
30
30
30
30
30
30
30
30
30
30
10
20
40
70
86
81
73
52
95
39
89
95
96
75
81
96
2
Ethanol
3
Acetonitrile
Dichloromethane
Toluene
4
5
6
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
Solvent free
7
8
5
9
20
30
10
10
10
10
11
12
13
aReaction conditions: Benzaldehyde (1 mmol), 3-(trifluoromethyl)aniline (1 mmol), diethyl phosphite (1.2 mmol), nickel-based metal–organic framework
(catalyst), and solvent (3 mL) at room temperature.
bIsolated yield.
only 31%–47% yield of the final product (Table 2, Entries
1–3). These observations would emphasize the advan-
tages of using the Ni-MOF catalyst.
TABLE 2 A comparison of the efficiency of nickel-based
metal–organic framework (Ni-MOF) with other catalystsa
Catalyst
amount (mg)
Time
(min)
Yield
(%)b
Different derivatives of α-aminophosphonate could be
synthesized using the optimized reaction conditions
(Table 3). A wide range of electron-withdrawing or
electron-donating substituted aldehydes, including –Br, –
Cl, –F, –OH, –OCH3, and –NO2 groups, were compatible
with the optimized condition. All the electron-
withdrawing or electron-donating substrates underwent
reaction smoothly to afford the desired products in 80%–
98% yields. In case of 2-thiophenecarboxaldehyde and
ferrocene carbaldehyde, an excellent product was
obtained in short period (Table 3, Entries 22 and 23). The
synthesized α-aminophosphonate compounds were char-
acterized by IR, 1H NMR, 13C NMR spectra, GC–MS, and
elemental analysis (Supporting information).
Entry Catalyst
1
NiCl2
20
30
30
30
30
30
30
30
34
31
47
71
75
88
95
2
Ni(NO3)2 20
Ni(OAc)2 20
3
4c
5d
6e
7
Ni-BDC
Ni-BTC
Ni-NDC
Ni-MOF
10
10
10
10
aReaction conditions: Benzaldehyde (1 mmol), 3-(trifluoromethyl)aniline
(1 mmol), diethyl phosphite (1.2 mmol), and catalyst at room temperature.
bIsolated yield.
c,d,eSynthesized according to Sel and co-workers.[32]
4a.
(Phenyl-[3-trifluoromethyl-phenylamino]-
dimensions of Ni-MOF, which provide more catalytic
active sites that are responsible for catalysis (Table 2,
Entry 7). Moreover, Ni-BDC Ni-BTC, and Ni-NDC
yielded 71%, 75%, and 88% of the product (Table 2,
Entries 4–6). However, it was observed that the reaction
using NiCl2, Ni(NO3)2, and Ni(OAc)2 as catalyst gave
methyl)-phosphonic acid diethyl esterꢀ Yield 95%
(white solid); melting point (MP) = 104–107 C. IR (KBr,
υ
max/cm−1): 3294 (N–H), 1229 (P=O), 1054, 1013 (P–O–
1
C), H NMR (300 MHz, CDCl3) δ = 7.47 (d, 2H, Ar),
7.39–7.22 (m, 3H, Ar), 7.17 (t, 1H, Ar), 7.06–6.60 (m, 3H,
Ar), 5.27–5.06 (t, 1H, –NH), 4.76 (dd, 1H, –CH), 4.24–3.56

SYNTHESIS OF NEW α-AMINOPHOSPHONATES USING NANOSCALE NI-MOF
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TABLE 3 Scope of different aldehydes for the synthesis of α-aminophosphonatesa
Entry
1
R
Product
4a
Time (min)
Yield (%)b
Benzaldehyde
30
30
45
45
45
30
30
45
60
60
45
45
45
45
60
45
60
60
60
45
60
60
45
45
95c
94
98
93c
95
96
98
96
95
96
95
95
92
91
94
90
90
90
92
90
96
97
94
90
2
2-Methoxybenzaldehyde
3-Methoxybenzaldehyde
4-Methoxybenzaldehyde
3,4-Dimethoxybenzaldehyde
2,5-Dimethoxybenzaldehyde
3,4,5-Trimethoxybenzaldehyde
2-Hydroxy-3-methoxybenzaldehyde
3-Hydroxybenzaldehyde
4-Hydroxybenzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzaldehyde
2-Fluorobenzaldehyde
3-Fluorobenzaldehyde
4-Fluorobenzaldehyde
3,4-Difluorobenzaldehyde
4-(Trifluoromethyl)benzaldehyde
2-Nitrobenzaldehyde
4b
4c
3
4
4d
4e
5
6
4f
7
4g
8
4h
4i
9
10
11
12
13
14
15
16
17
18
119
20
21
22
23
24
4j
4k
4l
4m
4n
4o
4p
4q
4r
3-Nitrobenzaldehyde
4s
4-(Dimethylamino)benzaldehyde
4-(Benzyloxy)benzaldehyde
Ferrocene carbaldehyde
2-Thiophenecarboxaldehyde
3,5-Dimethylbenzaldehyde
4t
4u
4v
4w
4x
aReaction condition: Aldehydes (1 mmol), 3-(trifluoromethyl)aniline (1 mmol), diethyl phosphite (1.2 mmol), nickel-based metal–organic framework (10 mg),
and solvent-free condition at room temperature.
bIsolated yield.
cReported compound.
(m, 4H, –OCH2CH3), 1.29 (t, 3H, –OCH2CH3), 1.10 (t,
3H, –OCH2CH3). 13C NMR (75 MHz, CDCl3) δ = 146.83
(d, J = 14.6 Hz), 135.39 (d, J = 2.6 Hz), 131.40 (d, J = 31.8
Hz), 129.58, 128.72 (d, J = 2.6 Hz), 128.05 (dd, J = 18.0,
4.4 Hz), 124.22 (d, J = 272.3 Hz), 116.31 (s), 114.58 (q, J =
3.8 Hz), 110.60 (q, J = 3.9 Hz), 63.51 (d, J = 7.0 Hz, –
calcd. for C18H21F3NO3P: C, 55.82; H, 5.46; N, 3.62;
found: C, 55.71; H, 5.35; N, 3.54.
4b. ([2-Methoxy-phenyl]-[3-trifluoromethyl-phe-
nylamino]-methyl)-phosphonic acid diethyl ester
Yield 94% (white solid); MP = 143–146 ꢀC. IR (KBr,
υ
max/cm−1): 3276 (N–H), 1228 (P=O), 1043, 1019 (P–O–
1
OCH2CH3), 63.27 (d,
J
=
7.1 Hz, –OCH2CH3),
C), H NMR (300 MHz, CDCl3) δ = 7.48 (d, 1H, Ar),
7.34–6.84 (m, 6H, Ar), 6.74 (d, 1H, Ar), 5.39 (dd, 1H, –
CH), 5.09 (t, 1H, –NH), 4.33–4.07 (m, 2H, –OCH2CH3),
56.87–54.86 (J = 151.7 Hz, –CH), 16.42 (d, J = 5.8 Hz, –
OCH2CH3), 16.16 (d, J = 5.8 Hz, –OCH2CH3). Anal.

8 of 14
RASAL ET AL.
1
4.08–3.39 (m, 5H, –OCH3 and –OCH2CH3), 1.32 (t, 3H, –
OCH2CH3), 1.03 (t, 3H, –OCH2CH3). 13C NMR (75 MHz,
CDCl3) δ = 157.27 (d, J = 6.6 Hz), 146.78 (d, J = 14.8 Hz),
131.39 (d, J = 31.7 Hz), 126.11, 123.99, 122.51, 121.13 (d, J
= 2.8 Hz), 116.68, 114.47 (d, J = 2.8 Hz), 110.52 (d, J = 1.9
Hz), 109.85 (d, J = 4.0 Hz), 63.36 (d, J = 7.1 Hz, –
OCH2CH3), 63.07 (d, J = 6.9 Hz, –OCH2CH3), 55.73 (–
OCH3), 48.55–46.49 (J = 155.8 Hz, –CH), 16.44 (d, J = 5.9
Hz, –OCH2CH3), 16.09 (d, J = 5.9 Hz, –OCH2CH3). Anal.
calcd. for C19H23F3NO4P: C, 54.68; H, 5.55; N, 3.36;
found: C, 54.68; H, 5.35; N, 3.06. GC–MS (electron ioniza-
tion [EI]) m/z (%) calcd.: 417; found: 417, 280.
C), H NMR (300 MHz, CDCl3) δ = 7.23–7.01 (m, 2H,
Ar), 6.98–6.67 (m, 5H, Ar), 5.37 (dd, 1H, –CH), 5.16 (t,
1H, –NH), 4.19 (m, 2H, –OCH2CH3), 4.04–3.81 (m, 4H, –
OCH3 and –OCH2CH3), 3.81–3.55 (m, 4H, –OCH2CH3
and –OCH3), 1.32 (t, 3H, –OCH2CH3), 1.07 (t, 3H, –
OCH2CH3). 13C NMR (75 MHz, CDCl3) δ = 153.98 (d, J
= 3.0 Hz), 151.57 (d, J = 6.6 Hz), 146.75 (d, J = 14.8 Hz),
131.42 (q, J = 31.7 Hz), 129.51, 125.05, 116.73, 114.57 (q,
J = 3.9 Hz), 114.11 (dd, J = 6.2, 3.8 Hz), 111.66 (d, J = 2.0
Hz), 109.85 (q, J = 4.0 Hz), 63.39 (J = 7.0 Hz, –
OCH2CH3), 63.11 (J = 6.9 Hz, –OCH2CH3), 56.27 (–
OCH3), 55.66–47.74 (J = 155.3 Hz, –CH), 16.44 (J = 5.8
Hz, –OCH2CH3), 16.14 (J = 5.9 Hz, –OCH2CH3). Anal.
calcd. for C20H25F3NO5P: C, 53.69; H, 5.63; N, 3.13;
found: C, 53.60; H, 5.43; N, 3.01.
4d. ([4-Methoxy-phenyl]-[3-trifluoromethyl-phe-
nylamino]-methyl)-phosphonic acid diethyl ester
Yield 93% (white solid); MP = 111–113 ꢀC. IR (KBr,
υ
max/cm−1): 3306 (N–H), 1229 (P=O), 10459, 1038 (P–O–
4g. ([3-Trifluoromethyl-phenylamino]-[3,4,5-tri-
methoxy-phenyl]-methyl)-phosphonic acid diethyl
ester Yield 98% (white solid); MP = 117–119 ꢀC. IR
(KBr, υmax/cm−1): 3301 (N–H), 1231 (P=O), 1030, 1012
1
C), H NMR (300 MHz, CDCl3) δ = 7.51–7.33 (m, 2H,
Ar), 7.17 (t, 1H, Ar), 6.96–6.83 (m, 4H, Ar), 6.71 (d, 1H,
Ar), 5.14 (t, 1H, –NH), 4.71 (dd, 1H, –CH), 4.12 (m, 2H, –
OCH2CH3), 4.00–3.64 (m, 5H, –OCH2CH3 and –OCH3),
1.21 (tt, 6H, –OCH2CH3). 13C NMR (75 MHz, CDCl3) δ =
159.49 (d, J = 2.8 Hz), 146.69 (d, J = 14.6 Hz), 131.42 (q, J
= 31.8 Hz), 129.59, 128.98 (d, J = 5.6 Hz), 127.01 (d, J =
2.6 Hz), 125.98, 122.37, 116.52, 114.70 (d, J = 3.9 Hz),
114.19 (d, J = 1.8 Hz), 110.44 (d, J = 3.8 Hz), 63.46 (J =
7.0 Hz, –OCH2CH3), 63.20 (J = 7.1 Hz, –OCH2CH3),
56.21 (–OCH3), 55.24–54.18 (J = 80.5 Hz, –CH), 16.44
(J = 5.8 Hz, –OCH2CH3), 16.26 (J = 5.7 Hz, –OCH2CH3).
Anal. calcd. for C19H23F3NO4P: C, 54.68; H, 5.55; N, 3.36;
found: C, 53.61; H, 5.35; N, 3.06.
1
(P–O–C), H NMR (300 MHz, CDCl3) δ = 7.22 (t, 1H,
Ar), 7.03–6.86 (m, 2H, Ar), 6.72 (m, 3H, Ar), 5.17–4.94
(t, 1H, –NH), 4.67 (dd, 1H, –CH), 4.13 (m, 2H, –
OCH2CH3), 4.06–3.79 (m, 10H, –OCH2CH3 and –
OCH3), 3.72 (m, 1H, –OCH2CH3), 1.30 (t, 3H, –
OCH2CH3), 1.15 (t, 3H, –OCH2CH3). 13C NMR
(75 MHz, CDCl3) δ = 153.50 (d, J = 2.7 Hz), 146.83
(d, J = 14.3 Hz), 137.88 (d, J = 3.6 Hz), 132.39–130.63,
129.69, 126.01, 122.40, 116.55, 114.90, 111.24–109.22,
104.94, 63.53 (d, J = 7.0 Hz, –OCH2CH3), 63.29 (d, J
= 7.1 Hz, –OCH2CH3), 60.86 (d, –OCH3), 57.21 (–
OCH3), 56.19–55.19 (–CH), 16.46 (d, J = 5.8 Hz, –
OCH2CH3), 16.29 (d, J = 5.8 Hz, –OCH2CH3). Anal.
calcd. for C21H27F3NO6P: C, 52.83; H, 5.70; N, 2.93;
found: C, 52.51; H, 5.49; N, 2.75.
4e. ([3,4-Dimethoxy-phenyl]-[3-trifluoromethyl-
phenylamino]-methyl)-phosphonic aciꢀd diethyl
ester Yield 95% (white solid); MP = 90–93 C. IR (KBr,
υ
max/cm−1): 3301 (N–H), 1230 (P=O), 1056, 1030 (P–O–
1
C), H NMR (300 MHz, CDCl3) δ= 7.19 (t, 1H, Ar), 6.93
(m, 5H, Ar), 6.72 (d, 1H, Ar), 5.01 (s, 1H, –NH), 4.70 (d,
1H, –CH), 4.21–3.60 (m, 10H, –OCH3 and –OCH2CH3),
1.30 (t, 3H, –OCH2CH3), 1.14 (t, 3H, –OCH2CH3). 13C
NMR (75 MHz, CDCl3) δ = 149.11 (dd, J = 21.5, 2.8 Hz),
146.84 (d, J = 14.5 Hz), 131.44 (q, J = 31.8 Hz), 129.61,
127.60 (d, J = 2.7 Hz), 126.02, 122.41, 120.32 (d, J = 6.4
Hz), 116.58, 114.78, 111.24 (d, J = 2.4 Hz), 110.92 (d, J =
4.9 Hz), 110.63–110.25, 63.50 (J = 7.0 Hz, –OCH2CH3),
63.23 (J = 7.1 Hz, –OCH2CH3), 56.65 (–OCH3), 55.98 (–
OCH3), 55.87–54.62 (–CH), 16.45 (J = 5.8 Hz, –
OCH2CH3), 16.30 (J = 5.7 Hz, –OCH2CH3). Anal. calcd.
for C20H25F3NO5P: C, 53.69; H, 5.63; N, 3.13; found: C,
53.56; H, 5.39; N, 3.03. GC–MS (EI) m/z (%) calcd.: 447;
found: 447, 310.
4h. ([2-Hydroxy-3-methoxy-phenyl]-[3-trifluoro-
methyl-phenylamino]-methyl)-phosphonic
acid
ꢀ
diethyl ester Yield 96% (white solid); MP = 148–150 C.
IR (KBr, υmax/cm−1): 3465 (N–H), 1229 (P=O), 1058,
1011 (P–O–C), 1H NMR (300 MHz, CDCl3) δ = 6.97
(m, 7H, Ar), 6.41 (s, 1H, Ar), 5.26 (dd, 1H, –CH), 5.06
(t, 1H, –NH), 4.28–4.07 (m, 2H, –OCH2CH3), 4.06–3.58
(m, 5H, –OCH3 and –OCH2CH3), 1.31 (t, 3H, –
OCH2CH3), 1.10 (t, 3H, –OCH2CH3). 13C NMR
(75 MHz, CDCl3) δ = 146.81 (dd, J = 13.4, 8.0 Hz),
144.01 (d, J = 6.6 Hz), 131.45 (q, J = 31.8 Hz), 129.60,
125.11, 122.47, 121.62, 120.37, 118.91, 116.49,
115.00–113.77, 110.50, 110.33, 63.50 (J = 7.1 Hz, –
OCH2CH3), 63.34 (J = 7.0 Hz, –OCH2CH3), 56.09 (–
OCH3), 50.03–47.97 (J = 155.8 Hz, –CH), 16.42 (d, J =
5.8 Hz, –OCH2CH3), 16.14 (d, J = 5.7 Hz, –OCH2CH3).
Anal. calcd. for C19H23F3NO5P: C, 52.66; H, 5.35; N,
3.23; found: C, 52.56; H, 5.23; N, 3.02. GC–MS
(EI) m/z (%) calcd.: 433; found: 433, 295.
4f. ([2,5-Dimethoxy-phenyl]-[3-trifluoromethyl-
phenylamino]-methyl)-phosphonic acid diethyl
ester Yield 96% (white solid); MP = 127–130 ꢀC. IR (KBr,
υ
max/cm−1): 3310 (N–H), 1230 (P=O), 1056, 1021 (P–O–

SYNTHESIS OF NEW α-AMINOPHOSPHONATES USING NANOSCALE NI-MOF
9 of 14
4i. ([3-Hydroxy-phenyl]-[3-trifluoromethyl-phe-
nylamino]-methyl)-phosphonic acid diethyl ester
Yield 95% (white solid); MP = 149–152 ꢀC. IR (KBr,
C), 1H NMR (300 MHz, CDCl3) δ = 7.26–7.15(m, 3H,
Ar), 6.93–6.86 (m, 2H, Ar), 6.73–4.67 (dd, 3H, Ar),
4.15–4.10 (d, 1H, –CH), 4.07–3.92 (m, 3H, –OCH2CH3),
3.78–3.73 (m, 1H, –OCH2CH3), 1.29–1.25(t, 3H, –
OCH2CH3), 1.16–1.11 (t, 3H, –OCH2CH3). 13C NMR
(75 MHz, CDCl3) δ = 162.58 (dd, J = 247.0, 3.4 Hz),
146.57 (d, J = 14.6 Hz), 132.48–130.74, 129.72–129.36,
125.96, 122.35, 116.41, 115.74, 115.16–114.48, 110.52,
63.51 (d, J = 7.2 Hz, –OCH2CH3), 63.40 (d, J = 7.2 Hz, –
OCH2CH3), 56.21–54.19 (J = 152.5 Hz, –CH), 16.43 (d,
J = 5.7 Hz, –OCH2CH3), 16.22 (d, J = 5.7 Hz, –
OCH2CH3). Anal. calcd. for C18H20F4NO3P: C, 53.34; H,
4.97; N, 3.46: found: C, 53.01; H, 4.80; N, 3.12. GC–MS
(EI) m/z (%) calcd.: 405; found: 405, 267, 172, 145.
υ
max/cm−1): 3310 (N–H), 1231 (P=O), 1049, 1018 (P–O–
1
C), H NMR (300 MHz, CDCl3) δ = 7.27–7.05 (m, 3H,
Ar), 7.00–6.74 (m, 4H, Ar), 6.66 (d, 1H, Ar), 5.08 (s, 1H, –
NH), 4.71 (d, 1H, –CH), 4.23–3.80 (m, 3H, –OCH2CH3),
3.58 (m, 1H, –OCH2CH3), 1.28 (t, 3H, –OCH2CH3), 1.04
(t, 3H, –OCH2CH3). 13C NMR (75 MHz, CDCl3) δ =
157.41 (d, J = 3.0 Hz), 146.48 (d, J = 14.3 Hz), 136.34 (d,
J = 2.4 Hz), 131.44, 129.98, 124.13, 120.04, 116.37, 116.06,
114.86, 114.14, 110.44, 64.22 (d, J = 7.2 Hz, –OCH2CH3),
63.68 (d, J = 7.3 Hz, –OCH2CH3), 55.71 (J = 152.9 Hz, –
CH), 16.32 (d, J = 5.8 Hz, –OCH2CH3), 16.05 (d, J = 5.7
Hz, –OCH2CH3). Anal. calcd. for C18H21F3NO4P: C,
53.60; H, 5.25; N, 3.47;
4q. ([4-Trifluoromethyl-phenyl]-[3-trifluorome-
thyl-phenylamino]-methyl)-phosphonic acid diethyl
ester Yield 90% (white solid); MP = 103–105 ꢀC. IR (KBr,
4j. ([4-Hydroxy-phenyl]-[3-trifluoromethyl-phen-
ylamino]-methyl)-phosphonic acid diethyl ester
Yield 96% (white solid); MP = 96–98 ꢀC. IR (KBr,
υ
max/cm−1): 3280 (N–H), 1228 (P=O), 1048, 1015 (P–O–
C), 1H NMR (300 MHz, CDCl3) δ = 7.61 (s, 4H, Ar), 7.19
(t, 1H, Ar), 6.95 (d, 1H, Ar), 6.85 (s, 1H, Ar), 6.66 (d, 1H,
Ar), 5.31–5.14 (t, 1H, –NH), 4.83 (dd, 1H, –CH), 4.24–3.72
(m, 4H, –OCH2CH3), 1.31 (t, 3H, –OCH2CH3), 1.16 (t,
3H, –OCH2CH3). 13C NMR (75 MHz, CDCl3) δ = 146.48
(d, J = 14.4 Hz), 139.90, 132.02 (d, J = 31.9 Hz), 130.41,
129.77, 128.25, 125.95, 125.70, 122.27, 116.17, 115.04,
110.68, 63.68 (d, J = 7.2 Hz, –OCH2CH3), 63.58 (d, J = 7.2
Hz, –OCH2CH3), 56.68–54.68 (J = 150.8 Hz, –CH), 16.44
(d, J = 5.7 Hz, –OCH2CH3), 16.19 (d, J = 5.7 Hz, –
OCH2CH3). Anal. calcd. for C19H20F6NO3P: C, 50.12; H,
4.43; N, 3.08; found: C, 50.00; H, 4.13; N, 2.98.
υ
max/cm−1): 3361 (N–H), 1229 (P=O), 1058, 1018 (P–O–
1
C), H NMR (300 MHz, CDCl3) δ = 7.57–7.32 (m, 2H,
Ar), 7.26–6.78 (m, 5H, Ar), 6.69 (d, 1H, Ar), 5.36–5.02 (t,
1H, –NH), 4.75 (dd, 1H, –CH), 4.29–3.87 (m, 3H, –
OCH2CH3), 3.84–3.64 (m, 1H, –OCH2CH3), 1.22 (m, 6H,
–OCH2CH3). 13C NMR (75 MHz, CDCl3) δ = 156.87 (d,
J = 2.7 Hz), 146.56 (d, J = 14.3 Hz), 131.45 (q, J = 32.0
Hz), 129.63, 125.33, 122.37, 116.71, 116.08, 114.90, 110.48,
63.80 (d, J = 6.8 Hz, –OCH2CH3), 63.71 (d, J = 7.1 Hz, –
OCH2CH3), 56.13–54.08 (J = 154.7 Hz, –CH), 16.34 (d,
J = 5.6 Hz, –OCH2CH3), 16.16 (d, J = 5.7 Hz, –
OCH2CH3). Anal. calcd. for C18H21F3NO4P: C, 53.60; H,
5.25; N, 3.47; found: C, 53.10; H, 5.01; N, 3.13.
4r. ([2-Nitro-phenyl]-[3-trifluoromethyl-phenyl-
amino]-methyl)-phosphonic acid diethyl ester Yield
90% (buff solid); MP = 145–147 C. IR (KBr, υmax/cm−1):
ꢀ
4l.
([4-Bromo-phenyl]-[3-trifluoromethyl-
1
phenylamino]-methyl)-phosphonic acid diethyl
3301 (N–H), 1231 (P=O), 1042, 1011 (P–O–C), H NMR
ꢀ
ester Yield 95% (white solid); MP = 99–101 C. IR (KBr,
(300 MHz, CDCl3) δ = 8.02 (d, 1H, Ar), 7.76 (d, 1H, Ar),
7.50 (m, 2H, Ar), 7.22 (t, 1H, Ar), 7.09–6.88 (m, 2H, Ar),
6.81 (d, 1H, Ar), 6.18 (dd, 1H, –CH), 5.62 (t, 1H, –NH),
4.19 (m, 2H, –OCH2CH3), 4.05–3.63 (m, 2H, –OCH2CH3),
1.32 (t, 3H, –OCH2CH3), 1.11 (t, 3H, –OCH2CH3). 13C
NMR (75 MHz, CDCl3) δ = 149.55 (d, J = 5.5 Hz), 146.16
(d, J = 14.5 Hz), 133.51 (d, J = 3.0 Hz), 131.71, 131.16,
129.93, 128.86, 125.93, 125.28, 122.32, 115.67, 115.01,
110.89, 64.01 (d, J = 7.2 Hz, –OCH2CH3), 63.52 (d, J = 7.2
Hz, –OCH2CH3), 50.73–48.71 (J = 150.8 Hz, –CH), 16.38
(d, J = 5.7 Hz, –OCH2CH3), 15.94 (d, J = 5.7 Hz, –
OCH2CH3). Anal. calcd. for C18H20F3N2O5P: C, 50.01; H,
4.66; N, 6.48; found: C, 49.97; H, 4.60; N, 6.39. GC–MS
(EI) m/z (%) calcd.: 432; found: 432, 295, 145.
υ
max/cm−1): 3298 (N–H), 1231 (P=O), 1053, 1021 (P–O–
1
C), H NMR (300 MHz, CDCl3) δ = 7.52–7.34 (dd, 4H,
Ar), 7.18 (t, 1H, Ar), 7.03–6.81 (m, 2H, Ar), 6.67 (d, 1H,
Ar), 5.51–5.30 (t, 1H, –NH), 4.73 (dd, 1H, –CH), 4.24–3.94
(m, 3H, –OCH2CH3), 3.86–3.67 (m, 1H, –OCH2CH3), 1.23
(m, 6H, –OCH2CH3). 13C NMR (75 MHz, CDCl3) δ =
146.47 (d, J = 14.5 Hz), 134.03 (d, J = 3.0 Hz), 131.75 (t,
J = 31.9 Hz), 129.64, 129.17, 128.94, 125.93, 122.32,
116.36, 114.95, 110.53, 64.10–62.68, 56.35–54.34 (J =
151.6 Hz, –CH), 16.41 (J = 5.7 Hz, –OCH2CH3), 16.22
(J
=
5.7 Hz, –OCH2CH3). Anal. calcd. for
C18H20BrF3NO3P: C, 46.37; H, 4.32; N, 3.00; found: C,
46.07; H, 4.00; N, 2.96. GC–MS (EI) m/z (%) calcd.: 466;
found: 465, 328, 172, 145.
4s. ([3-Nitro-phenyl]-[3-trifluoromethyl-phenyla-
mino]-methyl)-phosphonic acid diethyl ester Yield
92% (yellow solid); MP = 116–118 ꢀC. IR (KBr,
4o. ([4-Fluoro-phenyl]-[3-trifluoromethyl-phen-
ylamino]-methyl)-phosphonic acid diethyl ester
Yield 94% (white solid); MP = 106–108 ꢀC. IR (KBr,
υ
max/cm−1): 3295 (N–H), 1236 (P=O), 1046, 1019 (P–O–
υ
max/cm−1): 3297 (N–H), 1224 (P=O), 1048, 1017 (P–O–
C), 1H NMR (300 MHz, CDCl3) δ = 8.36 (s, 1H, Ar), 8.17

10 of 14
RASAL ET AL.
(d, 1H, Ar), 7.84 (d, 1H, Ar), 7.54 (t, 1H, Ar), 7.21 (t, 1H,
Ar), 6.97 (d, 1H, Ar), 6.85 (s, 1H, Ar), 6.68 (d, 1H, –CH),
5.47–5.23 (t, 1H, –NH), 4.92–4.88 (dd, 1H, –OCH2CH3),
4.31–3.79 (m, 4H, –OCH2CH3), 1.32 (t, 3H, –OCH2CH3),
1.19 (t, 3H, –OCH2CH3). 13C NMR (75 MHz, CDCl3) δ =
148.53 (d, J = 3.0 Hz), 146.28 (d, J = 14.2 Hz), 138.33 (d,
J = 2.5 Hz), 133.86 (d, J = 5.0 Hz), 131.60 (q, J = 31.9
Hz), 129.82, 129.66, 125.88, 123.16, 122.76, 116.10, 115.22,
110.69, 63.89 (d, J = 7.1 Hz, –OCH2CH3), 63.63 (d, J = 7.1
Hz, –OCH2CH3), 56.39–54.38 (J = 151.3 Hz, –CH), 16.43
(d, J = 5.7 Hz, –OCH2CH3), 16.22 (d, J = 5.7 Hz, –
OCH2CH3). Anal. calcd. for C18H20F3N2O5P: C, 50.01; H,
4.66; N, 6.48; found: C, 49.90; H, 4.60; N, 6.37.
4w. (Thiophen-2-yl-[3-trifluoromethyl-phenyla-
mino]-methyl)-phosphonic acid diethyl ester Yield
94% (white solid); MP
=
96–99 ꢀC. IR (KBr,
υ
max/cm−1): 3296 (N–H), 1227 (P=O), 1043, 1012 (P–
O–C), 1H NMR (300 MHz, CDCl3) δ = 7.36–7.13 (m,
3H, Ar), 6.97 (dd, 3H), 6.81 (m, 1H, Ar), 5.27–4.91 (m,
2H, –CH and –NH), 4.28–3.74 (m, 4H, –OCH2CH3),
1.24 (m, 6H, –OCH2CH3). 13C NMR (75 MHz, CDCl3)
δ = 146.55 (d, J = 13.1 Hz), 138.99 (d, J = 1.7 Hz),
131.50 (q, J = 31.9 Hz), 129.67, 127.19, 126.54, 125.54,
122.3, 116.59, 115.19, 110.56, 63.70 (d, J = 3.6 Hz, –
OCH2CH3), 63.60 (d,
J = 3.6 Hz, –OCH2CH3),
52.84–50.74 (J = 158.8 Hz, –CH), 16.42 (d, J = 5.8 Hz,
–OCH2CH3), 16.26 (d, J = 5.8 Hz, –OCH2CH3). Anal.
calcd. for C16H19F3NO3PS: C, 48.85; H, 4.87; N, 3.56;
found: C, 48.59; H, 4.70; N, 3.46; S, 8.00. GC–MS
(EI) m/z (%) calcd.: 393; found: 393, 256.
4t. ([4-Dimethylamino-phenyl]-[3-trifluorometh-
yl-phenylamino]-methyl)-phosphonic acid diethyl
ester Yield 90% (white solid); MP = 102–104 ꢀC. IR (KBr,
υ
max/cm−1): 3279 (N–H), 1226 (P=O), 1058, 1016 (P–O–
C), 1H NMR (300 MHz, CDCl3) δ = 7.31 (d, 2H, Ar), 7.16
(t, 1H, Ar), 6.89 (d, 2H, Ar), 6.70 1(t, 3H, Ar), 5.03 (t, 1H,
–NH), 4.66 (dd, 1H, –CH), 4.12 (m, 1H, –OCH2CH3),
4.01–3.81 (m, 1H, –OCH2CH3), 3.65 (m, 1H, –OCH2CH3),
2.92 (s, 6H, –CH3), 1.29 (t, 3H, –OCH2CH3), 1.13 (t, 3H, –
OCH2CH3). 13C NMR (75 MHz, CDCl3) δ = 150.35 (d,
J = 2.4 Hz), 146.96 (d, J = 14.6 Hz), 131.33 (q, J = 31.7
Hz), 129.52, 128.67, 124.26, 122.20, 116.50, 114.42, 112.54,
110.50, 63.39 (d, J = 7.0 Hz, –OCH2CH3), 63.03 (d, J = 7.0
Hz, –OCH2CH3), 56.21–54.17 (J = 154.2 Hz, –CH), 40.42
(–CH3), 16.45 (d, J = 5.7 Hz, –OCH2CH3), 16.30 (d, J =
5.7 Hz, –OCH2CH3). Anal. calcd. for C20H26F3N2O3P: C,
55.81; H, 6.09; N, 6.51; found: C, 55.70; H, 6.00; N, 6.36.
An excellent catalytic performance of Ni-MOF is due
to its higher surface area and large pore dimensions. In
metal carboxylates, the metal–oxygen bond (Mn+–O2−),
which acts as the Lewis acid site and basic site, respec-
tively, is responsible for catalysis. The plausible mecha-
nism for the synthesis of α-aminophosphonate over Ni-
MOF is depicted in Figure 6. In the mechanism, the
Lewis acid site of Ni-MOF activates the carbonyl group of
aldehyde to form imine. The Lewis acid site of Ni-MOF
further activates the imine and then the activated com-
plex reacts with diethyl phosphite to afford
α-aminophosphonate with regeneration of Ni-MOF for
further reaction.
FIGURE 6 Plausible mechanism for
α-aminophosphonate synthesis using nickel-based
metal–organic framework (Ni-MOF)

SYNTHESIS OF NEW α-AMINOPHOSPHONATES USING NANOSCALE NI-MOF
11 of 14
FIGURE 7 Recyclability of catalyst
FIGURE 8 (a) X-ray diffraction, (b) Fourier transform infrared, (c) thermogravimetry/differential thermal analysis, and (d) field-
emission scanning electron microscopy of nickel-based metal–organic framework (eighth run)

12 of 14
RASAL ET AL.
3.3 | Recycling of catalyst
and FESEM results of the recovered Ni-MOF
(Figure 8). The XRD of recycled Ni-MOF showed
slightly different crystallinity than the fresh Ni-MOF.
The FTIR spectra of recycled Ni-MOF exhibited a simi-
lar absorption as compared with that of fresh Ni-MOF.
The catalyst recycled after the eighth run shows a
slight decrease in the weight loss due to removal of
physically adsorbed solvent and other organic impuri-
ties. FESEM and BET studies of the recycled catalyst
show agglomerated nanoplatelets with decreases in
pore size of Ni-MOF due to use of the catalyst in sev-
eral reactions. The percentage of nickel present in
fresh and reused Ni-MOF was analyzed by inductively
coupled plasma atomic emission spectroscopy and was
found to be invariable.
The recyclability of the catalyst plays a vital role in indus-
trial and chemical processes. Ni-MOF was employed as a
recyclable catalyst in the formation of α-aminophos-
phonate via benzaldehyde and diethyl phosphite with
3-(trifluoromethyl)aniline under optimized reaction con-
ditions. The catalyst was separated from the reaction mix-
ture by centrifugation after each run and then washed
ꢀ
with ethanol and dried overnight at 80 C. Experimental
results indicated that the Ni-MOF catalyst could be
reused up to the eighth run. Indeed, the reaction still
afforded 85% yield in the eighth run (Figure 7). Further-
more, the catalyst Ni-MOF could be maintained during
the reaction as confirmed by XRD, FTIR, TG-DTA, BET,
TABLE 4 Antibacterial and antioxidant activities of novel α-aminophosphonate derivatives
Minimum inhibitory concentration (μg/mL)
2,2-Diphenyl-1-picrylhydrazyl
radical scavenging activity
Staphylococcus
aureus
Bacillus
subtilis
Escherichia
coli
Salmonella
typhi
Half-maximal inhibitory
concentration (μg/mL)
Compounds
4a
4b
4c
4d
4e
4f
250
250
15.62
250
125
250
250
250
125
125
125
31.25
125
250
250
125
250
62.5
62.5
15.62
125
250
62.5
62.5
31.25
250
–
250
250
62.5
125
125
125
250
125
62.5
125
125
125
62.5
250
250
250
125
250
62.5
62.5
62.5
125
31.25
62.5
125
250
–
312.61
105.85
343.07
269.75
380.35
320.27
738.55
55.26
125
31.25
250
62.5
250
31.25
125
250
250
250
4g
4h
4i
250
62.5
125
31.25
250
31.25
125
337.34
253.81
303.97
292.12
70.00
4j
62.5
62.5
31.25
125
4k
4l
31.25
62.5
250
4m
4n
4o
4p
4q
4r
4s
125
250
308.24
494.86
469.95
73.46
250
125
250
62.5
62.5
31.25
31.25
62.5
125
31.25
15.62
125
95.33
159.44
131.52
78.35
4t
31.25
250
4u
4v
4w
4x
7.81
15.62
62.5
15.62
31.25
31.25
125
59.33
75.61
174.4
Chloramphenicol 250
Ascorbic acid
–
–
–
33.70

SYNTHESIS OF NEW α-AMINOPHOSPHONATES USING NANOSCALE NI-MOF
13 of 14
3.4 | Antibacterial activity
acknowledge Microanalytical Laboratory and IRMRA
(Thane) for providing characterization facilities.
The newly synthesized compounds (4a–4x) were
tested for antibacterial activity against two Gram-
positive and Gram-negative bacteria using the REMA.
The antibacterial assay of the screened compounds
(4a–4x) was investigated by MIC (Table 4). The
antibacterial screening data revealed that the majority
of the compounds exhibited the same and high activ-
ity against both Gram-positive and Gram-negative
bacteria.
ORCID
Navinchandra G. Shimpi https://orcid.org/0000-0003-
0291-1804
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: Rasal SA, Dhavan PP,
Jadhav BL, Shimpi NG. Synthesis of new
α-aminophosphonates using nanoscale nickel-
based metal–organic framework as a
heterogeneous catalyst and their antibacterial
activity. Appl Organometal Chem. 2019;e5317.
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