Graphene Oxide as Recyclable Catalyst for One-Pot Synthesis of α-Aminophosphonates

Article abstract of DOI:10.1080/00397911.2014.989447

We report the synthesis of α-aminophosphonates from aromatic aldehydes, aromatic and aliphatic amines, and trimethylphosphite (Kabachnik-Fields reaction) using a "carbocatalyst," graphene oxide, at room temperature with excellent yield and recyclability. Enhanced catalytic activity of graphene oxide as compared to other catalysts studied is possibly due to the presence of carboxylic acid and hydroxyl groups. GRAPHICAL ABSTRACT.

Full text of DOI:10.1080/00397911.2014.989447

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Graphene Oxide as Recyclable Catalyst for One-Pot
Synthesis of α-Aminophosphonates
Kiran B. Dhoptea, Dnyaneshwar S. Rautb, Anand V. Patwardhana & Parag R. Nemadec
a Department of Chemical Engineering, Institute of Chemical Technology, Matunga, Mumbai
Maharashtra 400019, India
b Department of Chemistry, Dynopasak College, Parbhani, Maharashtra 431 401, India
c Department of Chemical Engineering and Department of Oils, Oleochemicals and
Surfactant Technology, Institute of Chemical Technology, N. Parekh Marg, Mumbai,
Maharashtra 400 019, India
Accepted author version posted online: 01 Dec 2014.
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To cite this article: Kiran B. Dhopte, Dnyaneshwar S. Raut, Anand V. Patwardhan & Parag R. Nemade (2014): Graphene Oxide
as Recyclable Catalyst for One-Pot Synthesis of α-Aminophosphonates, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, DOI: 10.1080/00397911.2014.989447
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Graphene Oxide as Recyclable Catalyst for One-Pot Synthesis of ɑ-Aminophosphonates
Kiran B. Dhopte1, Dnyaneshwar S. Raut2, Anand V. Patwardhan1, Parag R. Nemade3
1Department of Chemical Engineering, Institute of Chemical Technology, N. Parekh Marg, Matunga,
Mumbai Maharashtra 400019, India,2Department of Chemistry, Dynopasak College, Parbhani,
Maharashtra 431 401, India,3Department of Chemical Engineering and Department of Oils,
Oleochemicals and Surfactant Technology, Institute of Chemical Technology, N. Parekh Marg,
Mumbai, Maharashtra 400 019, India
Abstract
We report the synthesis of α-aminophosphonates from aromatic aldehydes, aromatic and aliphatic
amines and trimethylphosphite (Kabachnik-Fields Reaction) using a “carbocatalyst”, graphene oxide,
at room temperature with excellent yield and recyclability. Enhanced catalytic activity of graphene
oxide as compared to other catalysts studied is possibly due to presence of carboxylic acid and
hydroxyl groups.
KEYWORDS: Graphene oxide, ɑ-aminophosphonates, Aldehyde, Amine, Carbocatalyst
INTRODUCTION
α-Aminophosphonates are structurally and biologically analogous to amino
acids, hence their synthesis has attracted much interest. Their applications span from
being antitubercular, antioxidant, antimicrobial, antibacterial, anticancer agent, to
[9]
fungicides etc. [1-6] Lewis acids such as, SnCl4 [7], Tin (II) salts [8], Bi(OTf)3
,
nanoceria [10], BF3SiO2 [11], Yb(OTf)3 [12] zirconocenebis (perflorobutanesulfonate) [13]
,
AlCl3 [14] have been reported to catalyze the synthesis of α-aminophosphonates, however,
1

with reported disadvantages such as high cost, large amounts required, difficulty in
separation, limited reuse potential, unstable to moisture, etc.
Recent trends in chemical research have focused on developing metal-free synthetic
routes to minimize wastes, coupled with reuse of catalysts to decrease the environmental
footprint. Metal free, environment friendly, synthetic protocols for replacement of Lewis
acid catalysts using ultrasonication [15-16], organocatalysts (tartaric acid, oxalic acid,
(S)-1-acetyl-N-tosylpyrrolidine-2-carboxamide etc.) [17-19], baker yeast [20], sodium
dihydrogenphosphate [21], amberlyst-15 [22] have been reported. However, these catalysts
suffer from various drawbacks such as long reaction times, limited recyclability, or
difficulty in isolating the catalyst for reuse due to homogeneous nature, expensive or
require large amount of catalyst, etc.
Recently, much attention has been focused on the use of carbonaceous materials such
as natural graphite, activated carbon, reduced graphene oxide and functionalized carbon
material as heterogeneous catalysts as well as catalyst supports [23-26]. Graphene oxide has
been widely reported as an efficient catalyst for various organic transformations replacing
metal-based traditional pathways and is commonly known as “carbocatalyst” [27]
.
Graphene oxide exhibits localized charge distribution on the account of conjugated
aromatic skeleton and functional groups such as -COOH, -OH, epoxide, etc., which
makes it a suitable material for catalyst support. Graphene oxide is an excellent acid
2

catalyst with significant number of acid functional groups, its inherently insoluble nature,
low toxicity, ease of synthesis, separation and reuse. The reaction is benefitted by the
presence of additional acids, wherein large number of acidic sites on graphene oxide are
mechanistically advantageous. As the reaction proceeds via charge stabilization on imine
intermediate followed by phosphite attack, polar solvents are expected to enhance the
reaction. Graphene oxide disperses easily in polar solvents, hence graphene oxide
dispersed in polar solvents is expected be an efficient ‘green’ catalyst to replace
environmentally hazardous Lewis acid catalysts [28-31]. Herein, we report the use of
graphene oxide as heterogeneous catalyst for one pot synthesis of α-aminophosphonates
from aliphatic and aromatic amines, aromatic aldehydes, and trimethylphosphite at room
temperature with excellent yield, low catalyst loading and recyclability of catalyst.
RESULTS AND DISCUSSION
Catalyst Characterization
The presence of various functional groups on both edges of graphene oxide sheets after
successful exfoliation of natural graphite powder under strong oxidizing conditions were
characterized by FTIR, XRD, Zeta potential and HR-TEM analysis. FTIR spectrum (Fig.
1a) shows broad stretching band at 3457 cm-1, which can be attributed to hydroxyl groups
(υ O-H), whereas a sharp band at 1745 cm-1 confirms the presence of carbonyl groups (υ
C=O) in carboxylic acid. Additional bands at 1325 cm-1 and 1048 cm-1 can be attributed
3

to the presence of (υ C-O) stretching and epoxy groups respectively, thereby confirming
the presence of hydroxyl, carboxylic and epoxy groups.
Fig. 2 shows XRD pattern of both natural graphite powder and GO. XRD spectra of
natural graphite powder (Fig. 2a) displays sharp peak at 2θ = 26.8, corresponding to a
d-spacing of 0.33 nm, while the corresponding peak in the GO spectra (Fig. 2b) is present
at 2θ = 11.6 corresponds to (001) reflection indicating an interlayer spacing of d = 0.76
nm. This significant increment in the interlayer spacing can be ascribed to the insertion of
functional groups on both planes as well as edges of GO sheets. Fig. 3 shows HR TEM
image of graphene oxide nanosheets confirming that GO is made up of only a few layers
of graphene oxide as opposed to the flakes of graphite. This observation is significant as
it indicates that the graphene oxide nanosheeets will exhibit much large surface area than
graphite flakes, and hence is expected to show higher catalytic activity.
Fig. 4 gives ζ-potential (-34.8 mV) of dispersed graphene oxide, which shows the
localized surface charge distribution due to the presence of various functional groups.
Uniformly dispersed graphene oxide plays a key role for increased catalytic performance
due to high mobility of surface charges thereby stabilizing graphene oxide anions. Zeta
potential value i.e. (-34.8 mV) gives clear evidence of the presence of negatively charged
carboxylate groups which selectively catalyze Kabachnik-Fields reaction for synthesis of
α-aminophosphonates.
4

Catalyst Screening
The activity of the catalyst was studied by measuring the yield of α-aminophosphonate
in which 3 mg of graphene oxide catalyst was dispersed in solvents containing aromatic
aldehyde, amine (1 mmole) and trimethylphosphite in stoichiometric ratio at room
temperature under constant stirring. Table 1 presents a comparative study of yield of
reaction between benzaldehyde, aniline and trimethylphosphite as depicted in Scheme 1
using different catalysts. Graphene oxide gives better yield as well as shorter reaction
times than both Indion-130, a strongly acidic resin with sulphonic acid groups and
Indion-652, a weakly acidic resin with carboxylic acid groups. It must be noted that
stannic chloride, a Lewis acid shows slightly better yield for the same reaction time
without recyclability. Reduced graphene oxide, which is structurally similar but does not
have as many acidic groups as are present in graphene oxide, failed to catalyze the
reaction elucidating the beneficial effect of acidic groups present on graphene oxide and
confirming the carboxylate mediated pathway for the reaction.
The effect of solvents such as water, methanol, ethanol, dichloromethane and toluene
on the reaction was studied and is presented in Table 2. Since the reaction is aided by
polar solvents and graphene oxide disperses effectively in polar solvents, the reaction
performance is expected to be better in polar solvents than in nonpolar solvent. Among
the solvents studied, methanol was found to be the most effective solvent whereas toluene
was found to be a poor solvent for this reaction. In toluene, only trace yields were
5

observed, due to lack of dispersion of graphene oxide in toluene. Water was also found
to be a poor solvent with a reaction yield of only 25 % even though it is polar and
graphene oxide disperses excellently in water. The low reaction yield may perhaps be
attributed to sensitivity of phosphite to water.
The effect of presence of electron donating and electron withdrawing groups on
aromatic aldehydes and aromatic/aliphatic amines on the catalytic activity of graphene
oxide was studied and is presented in Table 3. Presence of electron withdrawing groups at
meta position on aldehyde (entry 2b, Table 3) gives better yield as compared to presence
of electron donating groups on aldehyde. (entry 3c–5e, Table 3). Both o-iodoaniline and
ethylenediamine required longer reaction times as compared to other substrates studied
(entry 10j and 11k, Table 3). Various aromatic amines substituted with electron
withdrawing group react cleanly with expected yields. (entry 7g–9i, Table 3).
One of the shortcomings of Lewis acid catalysts is their poor recyclability, which adds
to the environmental load of the process. Graphene oxide catalyst employed for the
reaction was, therefore, recycled in order to ascertain its reuse potential. The recycle
efficiency of graphene oxide was confirmed by carrying out four consecutive runs after
isolation from reaction mixture. For isolation of catalyst, the reaction mixture was
transferred to a separating funnel where the dispersed graphene oxide particles settled at
the bottom and were separated with ease. The separated catalyst was washed three times
6

with methanol to remove traces of any organic material adsorbed on catalyst surface. This
recycled catalyst exhibited sufficient catalytic activity and yield for reaction of
benzaldehyde, aniline and trimethylphosphite as per Scheme 1. No aggregation of
graphene oxide occurred during catalyst recycle procedures, therefore, the catalyst
maintains its dispersability on recycling. After recycling the catalyst four times, the
catalyst was analyzed using Fourier Transform Infrared (FTIR) spectroscopy to identify if
the catalyst has undergone any functional modification during the reaction. A narrowing
of –OH peak and reduction in the intensity of carbonyl peak was observed (Fig. 1b),
therefore there may be a reduction in the number of functional groups as the catalyst is
recycled. However, the yield and catalytic efficiency of graphene oxide was found to be
high which confirms excellent recyclability (Figure 5).
EXPRIMENTAL
All reagents were purchased from commercial sources and used as received. Natural
graphite flakes (325 mesh, Alfa Aesar), potassium carbonate (S D Fine Chem. Ltd.,
Mumbai), sulphuric acid (99%, Merck), nitric acid (99%, Merck), hydrogen peroxide
(30%, S D Fine Chem. Ltd., Mumbai), amines (99% Sigma Aldrich), trimethylphosphite
(99%, Lobachem), aldehydes (Sigma Aldrich) and used without any further purification.
General Procedure For Synthesis Of Α-Aminophosphonates
Aromatic aldehyde (1 mmole), amine (1 mmole) and trimethyl phosphite (1 mmole) were mixed with
well dispersed graphene oxide (3mg) in methanol and stirred at room temperature except for diamine
(Entry 11k, Table 3) where the molar amount of carbonyl compound and phosphite was twice as much
7

as the amine. The progress of the reaction was monitored by thin layer chromatography using a
solvent system consisting of a mixture of hexane and ethyl acetate (7:3). After completion, the catalyst
was separated from the reaction mass by decantation. The reaction mass was then quenched with 5%
NaHCO3 solution (3 mL). Crude product was extracted with dichloromethane (5 mL × 3). The organic
layer was again washed with 5% brine (3 mL) solution and dried over sodium sulphate for appropriate
time. The crude product was analyzed without further purification using various analytical techniques
such as MS, 1H NMR, 13C NMR, IR and Elemental analysis techniques.
CONCLUSIONS
In conclusion, we have demonstrated a simple and environmentally-friendly
methodology for one pot synthesis of α-aminophosphonates from aromatic aldehydes,
both aliphatic and aromatic amines, and trimethylphosphite using a metal free pathway
catalyzed by graphene oxide catalyst. Further, the catalyst offers simple workup, high
yield with excellent recyclability. We believe that this methodology can replace Lewis
acid catalyzed pathways for α-aminophosphonate synthesis without loss in yield, similar
reaction times and conditions.
SUPPORTING INFORMATION
Supplemental data for this article can be accessed on the publisher’s website.
ACKNOWLEDGEMENTS
The authors are greatly thankful to the University Grants Commission (UGC) of India
for providing Special Assistance Programme (SAP) fellowship, and DST FIST
programme of Department of Science and Technology, Govt. of India for support.
8

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Table 1. Effect of catalyst screening on synthesis of α-aminophosphonatesa
Entry Catalyst
Catalyst loading Time Yield (%)b
1
2
3
4
5
6
-
-
10
3
Trace
88
Graphene oxide
3 mg
Reduced graphene oxide 3 mg
-
-
Indion-130
Indion-652
SnCl2.H2O
30 mg
4
88
30 mg
7
85
10 (mol %)
3
91
a Reaction conditions: benzaldehyde (1 mmol), aniline (1 mmol), trimethylphosphite
(1mmol), graphene oxide (3 mg), methanol (3 mL), room temperature, time (3 h).
b Isolated yield.
12

Table 2. Effect of polar solvent on synthesis of α-aminophosphonatesa
Entry Catalyst
Yield (%)b
1
2
3
4
5
Water
25
88
Methanol
Dichloromethane 81
Ethanol
Toluene
85
trace
a Reaction conditions: benzaldehyde (1 mmol), aniline (1 mmol), trimethylphosphite
(1mmol), graphene oxide (3 mg), methanol (3 mL), room temperature, time (3 h).
b Isolated yield.
13

Table 3. Graphene oxide catalyzed synthesis of ɑ-aminophosphonate
Entry
1a
Aldehyde
Amine
Product
Time (h)
3
Yieldb (%)
88
O
NH2
HN
H
H
O
P
OCH3
OCH3
2b
3
85
NH2
O
HN
O
P OCH3
OCH3
Cl
Cl
3c
4
82
O
NH2
H
HN
O
N
P OCH3
OCH3
N
4d
5
6
81
86
O
NH2
H
HN
O
OH
P OCH3
OCH3
OH
CHO
5e
NH2
MeO
HN
O
P OCH3
OCH3
MeO
14

6f
7
4
78
86
O
NH2
O
NH
P OCH3
OCH3
7g
NO2
O
NH2
NO2
H
HN
O
P OCH3
OCH3
8h
4
86
Cl
O
NH2
Cl
H
HN
O
P OCH3
OCH3
9i
4
5
7
78
75
78
O
O
O
NH2
Br
Br
HN
HN
H
H
H
O
P OCH3
OCH3
10j
11k
NH2
I
I
O
P OCH3
OCH3
O
H
NH2
O
P
H2N
H3CO
H3CO
N
P
OCH3
OCH3
N
H
15

a Reaction conditions: Aldehyde (1 mmol), aromatic amine (1 mmol),
trimethylphosphite (1 mmole), graphene oxide (3 mg), methanol (3 mL), room
temperature.
b Isolated yield.
16

Scheme 1. α-aminophosphonate synthesis catalyzed by graphene oxide
17

Figure 1. FTIR spectra of (a) graphene oxide and (b) recycled graphene oxide.
18

Figure 2. XRD pattern of (a) graphite and (b) graphene oxide
19

Figure 3. HR-TEM image of Graphene oxide
20

Figure 4. Zeta potential result of graphene oxide
21

Figure 5. Recyclability study of graphene oxide as a catalyst for synthesis of
α-aminophosphonates.
22