A novel straightforward synthesis of α-aminophosphonates: one-pot three-component condensation of alcohols, amines, and diethylphosphite in the presence of CuO@Fe3O4 nanoparticles as a catalyst

Article abstract of DOI:10.1007/s11164-017-2890-y

We report here a novel and straightforward synthesis method for the preparation of α-aminophosphonates in relatively good yield. The method involves the one-pot three-component condensation of alcohols, amines, and diethylphosphite in the presence of CuO@Fe₃O₄ nanoparticles as a recyclable catalyst. CuO@Fe₃O₄ nanoparticles were prepared and their structures were confirmed by the FT-IR, TGA, VSM, TEM and X-ray diffraction patterns analyses.

Full text of DOI:10.1007/s11164-017-2890-y

Res Chem Intermed
DOI 10.1007/s11164-017-2890-y
A novel straightforward synthesis of a-aminophos-
phonates: one-pot three-component condensation
of alcohols, amines, and diethylphosphite in the
presence of CuO@Fe3O4 nanoparticles as a catalyst
Babak Kaboudin1,2 Foad Kazemi1 Narges Kadkhoda Hosseini1
•
•
Received: 7 November 2016 / Accepted: 2 February 2017
Ó Springer Science+Business Media Dordrecht 2017
Abstract We report here a novel and straightforward synthesis method for the
preparation of a-aminophosphonates in relatively good yield. The method involves
the one-pot three-component condensation of alcohols, amines, and diethylphos-
phite in the presence of CuO@Fe3O4 nanoparticles as a recyclable catalyst.
CuO@Fe3O4 nanoparticles were prepared and their structures were confirmed by
the FT-IR, TGA, VSM, TEM and X-ray diffraction patterns analyses.
Keywords CuO@Fe3O4 Nanoparticles Á Alcohols Á Amines Á
a-Aminophosphonates Á Oxidation Á Nanocatalyst
Introduction
Organophosphorus compounds are an important class of compounds that they have
a variety of interesting and useful properties in biological activities [1–8]. Recently,
the synthesis of a-substituted phosphonic derivatives has attracted significant
attention, due to their biological activities with broad application as enzyme
inhibitors, antimetabolites and antibiotics [9–11]. Among a-functionalized phos-
phonic acids, a-aminophosphonates, as phosphorus analogues of a-amino acids,
exhibit a variety of biological activities [12–17]. The Kabachnik–Fields [18–20]
method is a three-component condensation reaction of primary or secondary amines,
Electronic supplementary material The online version of this article (doi:10.1007/s11164-017-2890-y)
contains supplementary material, which is available to authorized users.
&
Babak Kaboudin
kaboudin@iasbs.ac.ir
1
2
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS),
Zanjan 45137-66731, Iran
Center for Research in Basic Sciences and Contemporary Technologies, IASBS, Zanjan, Iran
123

B. Kaboudin et al.
carbonyl compounds and dialkyl phosphites, and represents a convenient choice for
the synthesis of a-aminophosphonates. In general, these three-component reactions
may take place via hydrophosphorylation of a Schiff’s base imine catalyzed by a
base or an acid [21–23].
Magnetic nanoparticle-supported catalysts have attracted much attention in
developing greener and efficient catalytic reactions in organic transformations
[24–31]. These nanoparticles with highly active surface areas and readily dispersible
in the reaction system are very accessible to the reactants and can be simply
removed and readily reused from the reaction medium by an external magnet.
Different catalytic systems have been employed for the oxidation of alcohols to
carbonyl compounds [32–34]. Copper derivatives, especially copper halides and
oxides, are often employed for the oxidation process [35]. Due to loss of
homogenous copper catalysts at end of the reaction, different strategies have been
followed using supported copper catalysts on inorganic materials or immobilization
on organic–inorganic hybrid materials [36]. Recently, supported copper oxide on
magnetite has been reported as a nanocomposite in organic transformations [37].
Ramon et al. have reported synthesis of aromatic imines from alcohols and amines
using an impregnated copper on magnetite catalyst [38]. This report suggested to us
that the imines generated through the oxidation and condensation process of
alcohols with amines would react with diethyl phosphite in the presence of
CuO@Fe3O4 as a catalyst. To the best of our knowledge, there is no report on the
synthesis of a-aminophosphonates via a one-pot condensation of alcohols, amines
and diethyl phosphate. Therefore, as a part of our efforts to explore the utility of
magnetite nanoparticles for the synthesis of organophosphorus compounds [39, 40],
we decided to study the feasibility of the CuO@Fe3O4 nanocomposite as a catalyst
in a one-pot reaction of alcohols with amines and dialkyl phosphites for the
synthesis of a-aminophosphonates.
Results and discussion
The magnetic nanoparticles were prepared by simple co-precipitation of a mixture
of iron precursors (Fe2? and Fe3?) in the presence of an ammonia solution [41]. The
superparamagnetic CuO@Fe3O4 nanoparticles were prepared by hydrolysis and
condensation of copper (II) chloride in water at ambient temperature in the presence
of sodium hydroxide (Fig. 1) [38]. The morphology and structure of the prepared
CuO@Fe3O4 nanoparticles were characterized by TEM, XRD, and VSM which
FeCl3.4H2O
+
CuCl2
Fe3O4
Fe3O4
FeCl3.6H2O
+
NaOH, rt, pH=13
NH4OH
= CuO
Fig. 1 CuO@Fe3O4 nanoparticles preparation
123

A novel straightforward synthesis of a-aminophosphonates:…
confirmed the successful preparation of nanoparticles (see supporting information).
Incorporation of 4.82% (the weight percent) of Cu was measured by atomic
absorption spectrometry (Fig. 1). The nanoparticles sizes of CuO@Fe3O4 were
determined from the XRD pattern using Scherrer’s equation (the nanoparticle sizes
evaluated by Scherrer’s equation are 20 nm).
Initially, the reaction of benzyl alcohol 1a with aniline 2a was chosen as a model
for the in situ oxidative imine formation in the presence of CuO@Fe3O4
nanoparticles (Scheme 1). Treatment of 1a with aniline (1 equiv) at room
temperature in the absence of base in toluene failed to give the corresponding
imine 3a for 4 days (Entry 1). Ramon et al. have reported that using a base is
necessary in oxidative imine formation of alcohols [38]. However; the reaction did
not change upon adding the base (NaOH, 1.5 equiv) at room temperature for 4 days.
Heating of benzyl alcohol (1a) with aniline (2a) at 100 °C in the presence of NaOH
(1.5 equiv) with toluene for 24 h led to the formation of the desired imine 3a in 56%
yield (Table 1, Entry 3). The yield of the reaction was increased upon further
increase of the reaction time (Entries 4–6). The reaction yield was increased to 85%
yield after 4 days in the presence of 1.5 mol % of CuO@Fe3O4 (Entry 6). When the
catalyst loading was raised from 1.5 to 2.5%, the yield of 3a slightly increased to
86% (Entry 7). The yield of the reaction did not change upon further increase of the
catalyst or reaction time (Entries 8 and 9). When the reaction was carried out in
CH3CN and dioxane as a solvent, the reaction yield decreased to 14 and 33% yield,
respectively (Entries 10 and 11). Treatment of 1a with 2a at 100 °C in the presence
of Fe3O4 nanoparticles (1.5 mol %) gave the corresponding imine 3a in 8% yield
(Entries 12). Thus, the optimal reaction conditions for the oxidative imine formation
in the presence of CuO@Fe3O4 nanoparticles involved the use of 1.5 mol % of the
catalyst at 100 °C for 4 days.
In the next step, treatment of diethyl phosphite with a mixture of benzyl alcohol
1a and aniline 2a in the presence of CuO@Fe3O4 nanoparticles gave the
corresponding a-aminophosphonate 4a in 70% yield after 24 h (Scheme 2).
This process was successfully applied to other alcohol and aniline derivatives as
summarized in Table 2 (Scheme 3). Substituted benzyl alcohols reacted with a
mixture of aniline and diethylphosphite in the presence of 1.5 mol % of
CuO@Fe3O4 and NaOH (1.5 equiv) as the base to afford the desired products
4b–4e in moderate to good yields. However, treatment of p-nitrobenzyl alcohol with
aniline in the presence of diethyl phosphite under the same condition, failed to give
the expected a-aminophopsphonate (Entry 6) and that maybe is due to more
reactivity of the alcohol substrate to oxidize to corresponding carboxylic acid.
Substituted anilines also reacted with benzyl alcohol and diethyl phosphite under
optimized reaction conditions and gave the desired products 4f–4j in moderate to
Scheme 1 Reaction of benzyl
alcohol (1 equiv) with aniline (1
equiv) in the presence of
CuO@Fe3O4 as a catalyst
OH
NH2
N
CuO@Fe3O4
NaOH (1.5 equiv)
+
3a
1a
2a
123

B. Kaboudin et al.
Table 1 Reaction of benzyl alcohol (1 equiv) with aniline (1 equiv)
Entry
Mol % of
catalyst
Temperature
(°C)
Time
(d)a
Yield
b
%
3a
c
1
1.5
1.5
1.5
1.5
1.5
1.5
2.5
3.5
3.5
1.5
1.5
1.5
Rt
4
4
1
2
3
4
4
4
6
4
4
4
–
2
Rt
–
3
100
100
100
100
100
100
100
Reflux
100
100
56
73
83
85
86
86
86
14d
33e
8f
4
5
6
7
8
9
10
11
12
a
Reactions carried out in toluene
GC yield
b
c
d
e
f
Without any base
Acetonitrile as solvent
Dioxane as solvent
The reaction carried out in the presence of Fe3O4 nanoparticles
OH
1) CuO@Fe3O4 (1.5 mol%)
Toluene, NaOH(1.5 equiv)
100 °C, 4 days
NH2
O
P(OEt)2
+
O
NH
2)
, 100 °, 24 h
H P(OEt)2
1a
4a
2a
Scheme 2 Treatment of diethyl phosphite with a mixture of benzyl alcohol (1 equiv) and aniline
(1 equiv) in the presence of CuO@Fe3O4 as a catalyst
good yields (Entries 8–12). The process was also successfully applied for
1-naphthalenemethanol, and the compound 4j was obtained in 57% isolated yield
(Entry 12). Treatment of 1-butanol and furan-2-ylmethanol with aniline, and also
benzyl alcohol with butyl amine in the presence of diethyl phosphite under the same
condition, failed to give the expected a-aminophopsphonate (Entries 13–15).
The reusability of the CuO@Fe3O4 catalyst was also studied for the reaction of
benzyl alcohol 1a with aniline 2a and diethylphosphite in the presence of NaOH.
The nanoparticles were collected by an external magnet, and the particles was
washed four times with deionized water and methanol and reused after drying at
90 °C for 3 h for the synthesis of a-aminophosphonates. The catalytic activity did
not decrease considerably after four catalytic cycles (2% decreases after four
catalytic cycles).
123

A novel straightforward synthesis of a-aminophosphonates:…
Table 2 Reaction of alcohols 1 with amines 2 in the presence of diethylphosphite using CuO@Fe3O4
nanocatalyst
Entry
Alcohol 1
Amine 2
Product 4
Reaction Yield
31 P NMR
time (h)a
(%)b
δ (ppm) 4
OH
NH2
O
P(OEt)2
NH
2a
1a
4a
1
2
3
4
24
48
24
36
70
67
65
62
22.59
22.89
21.96
22.89
OH
NH2
MeO
O
P(OEt)2
NH
4b
2a
OMe
1b
OH
NH2
Cl
O
P(OEt)2
NH
2a
Cl
1c
4c
OH
NH2
O
P(OEt)2
NH
4d
2a
1d
OH
NH2
2a
O
5
48
66
22.59
P(OEt)2
NH
4e
1e
NH2
2a
OH
c
6
7
–
48
48
–
–
–
–
NO2
1f
NH2
OH
2a
c
–
NH2
1g
NH2
OH
O
P(OEt)2
NH
4f
OMe
1a
2b
8
9
48
24
63
69
22.69
22.19
MeO
OH
NH2
Br
O
P(OEt)2
NH
4g
1a
Br
2c
NH2
OH
O
10
11
24
24
70
72
22.73
21.26
P(OEt)2
NH
4h
Me
2d
2e
1a
Me
NH2
OH
O
P(OEt)2
NH
4i
NO2
O2
N
1a
123

B. Kaboudin et al.
Table 2 continued
Entry
12
Alcohol 1
Amine 2
Product 4
Reaction Yield
31 P NMR
δ (ppm) 4
22.94
time (h)a
(%)b
OH
NH2
24
57
O
P(OEt)2
2a
1h
NH
4j
NH2
d
OH
13
14
15
–
48
48
48
–
–
–
–
–
–
1i
2a
NH2
c
OH
–
O
1j
2a
OH
d
NH2
–
2f
1a
a
b
c
d
Reaction time is for second step
Yields refer to the isolated pure products after column chromatography
Unknown mixture
No reaction
1) CuO@Fe3O4 (1.5 mol%)
Toluene, NaOH(1.5 equiv)
O
R1
R2
P(OEt)2
100 °C, 4 days
R1
R2
+
NH2
O
OH
NH
2)
, 100 °C
H P(OEt)2
2
1
4
Scheme 3 Treatment of diethyl phosphite with a mixture of alcohol (1 equiv) and amine (1 equiv) in the
presence of CuO@Fe3O4 as a catalyst
A proposed mechanism is outlined in Scheme 4 for the synthesis of a-
aminophosphonates from the reaction of alcohols with amines in the presence of
diethyl phosphite using CuO@Fe3O4 nanoparticles. The present process is thought
to proceed via oxidative imine formation from alcohols and amines using
CuO@Fe3O4 nanoparticles, a known intermediate, followed by nucleophilic
addition of diethyl phosphite with the imine intermediate to give the a-
aminophosphonates 4. As shown in Scheme 4, a simple mechanism for CuO
catalyzed benzaldehyde formation from benzyl alcohol is in agreement with reports
by Riisager et al. [42]. The alcohol adsorbs on a copper site of the catalyst to form a
metal–alkoxide intermediate followed by abstraction of proton from the OH group
by oxygen on the surface of the catalyst. Subsequently, a b-H elimination process
occurs by Cu(II) to give Cu(I) hydride and a benzyl carbocation intermediate
followed by aldehyde formation. In the final step, atmospheric oxygen reacts with
123

A novel straightforward synthesis of a-aminophosphonates:…
OH
O
P(OEt)2
NH
Cu(II)
Cu(II)
O
OH
O
Fe3O4
H
H P(OEt)2
Cu(II)
N
= CuO
Cu(I)H
O
NH2
O2
Scheme 4 Proposed mechanism for the synthesis of a-aminophosphonate 4
the hydride forming the peroxide anion and regenerating the catalytic Cu(II) site.
Reaction of the peroxide anion with a second hydride reduces it further to hydroxide
anions [43, 44]. The reaction was carried out in an open flask, and we found no
difference in yield between the reactions carried out with or without air.
In conclusion, we have reported a novel and convenient method for the synthesis
of a-aminophosphonates via a one-pot condensation of alcohols, amines and diethyl
phosphite. A simple work-up, mild reaction conditions, moderate to good yields,
reusability of the catalyst, and clean reactions should make this method an attractive
and a useful contribution to present methodologies.
Experimental
General
All solvents and reagents were purchased from commercial sources and used
without further purification. All melting points were taken on a Yanagimoto and
Buchi 510 apparatus and are not corrected. NMR spectra were obtained on a Bruker
Avance 400 NMR spectrometer (1H NMR: 400 MHz, 13C NMR: 100 MHz, 31P
NMR: 162.0 MHz). Analytical TLC was carried out with Merck plates precoated
with silica gel 60 F254 (0.25 mm thick).
123

B. Kaboudin et al.
Procedure for the preparation of CuO@Fe3O4 nanoparticles catalyst
This catalyst was obtained according to the method reported in the literature [38].
FeCl3Á6H2O (4.72 g) and FeCl2Á4H2O (1.72 g) were dissolved in 40 mL distilled
water under stirring at 90 °C and argon gas. Then, 20 mL of ammonia (25%) was
added drop-wise to the reaction mixture with stirring. Prepared nanoparticles were
magnetically separated and washed with deionized water repeatedly and dried in
vacuum. Prepared Fe3O4 nanoparticles (4 g, 17 mmol) were added to a stirred
solution of CuCl2 (0.13 g, 1 mmol) in deionised water (120 mL). After 10 min at
room temperature, the mixture was slowly basified with NaOH 1 M until the pH
was around 13, and the mixture was stirred for 24 h and then filtrated under vacuum.
The solid catalyst was washed several times with deionised water (3 9 50 mL) and
dried for 3 days at room temperature.
General procedure for the synthesis of a-aminophosphonates (4) from the one-pot
three-component condensation of alcohols, amines, and diethylphosphite
To a mixture of CuO@Fe3O4 nanoparticles (40 mg, 1.3 mol % based on copper)
and NaOH (1.4 mmol, 56 mg) in toluene (3 mL), alcohol (1 mmol) and amine
(2 mmol) were added, and the mixture was stirred at 100 °C for 4 days in an open
flask. Diethylphosphite (1 mmol, 0.13 ml) was added to the reaction mixture, and
the mixture was stirred for 24–48 h (see Table 2) at 100 °C. The reaction progress
was monitored by TLC until the completion of the reaction. After cooling, EtOAc
(5 mL) was added to the reaction mixture, and the catalyst was separated by an
external magnet, washed thoroughly with methanol and distilled water and dried at
90 °C for 3 h for the next reaction. Then, the product was extracted by EtOAc
(3 9 10 mL). The combined organic phases were concentrated. The residue was
purified with column chromatography to give a-aminophosphonate 4 in 57–72%
isolated yield. All a-aminophosphonate 4 gave satisfactory spectral data in accord
with the assigned structures and literature reports.
O,O0-Diethyl [(anilino)phenylmethyl] phosphonate (4a) White solid (70%,
220 mg); mp: 91–93 °C [Lit [45]. 90–92 °C];1H NMR (400 MHz, CDCl3): d
(ppm) 1.15 (t, 3H, J = 7.2 Hz), 1.32 (t, 3H, J = 7.2 Hz), 3.67–3.74 (m, 1H),
3.94–4.00 (m,1H), 4.12–4.19 (m, 2H), 4.81 (d, 2H, br, NH ? CHP JPH = 24.0 Hz),
6.65(d, 2H, J = 8.0 Hz), 6.73 (t, 1H, J = 7.6 Hz), 7.14 (t, 2H, J = 7.6 Hz),
7.28–7.31 (m, 1H), 7.36 (t, 2H, J = 7.6 Hz), 7.52 (d, 2H, J = 7.2 Hz)13C NMR
(100 MHz, CDCl3): d (ppm) 16.2 (d, JPC = 6.0 Hz), 16.4 (d, JPC = 6.0 Hz), 55.6
(d, JPC = 150.0 Hz), 63.2 (d, JPC = 7.0 Hz) 63.3 (d, JPC = 7.0 Hz), 114.0, 118.5,
127.9, 127.9 (d, JPC = 4.0 Hz), 128.6 (d, JPC = 3.0 Hz), 129.20, 135.82 (d,
JPC = 3.0 Hz), 146.19 (d, JPC = 15.0 Hz) 31P NMR (162 MHz, CDCl3/H3PO4): d
(ppm) 22.59.
O,O0-Diethyl [(anilino)(4-methoxyphenyl)methyl] phosphonate (4b) White solid
(67%, 235 mg); mp: 105–107 °C [Lit [46]. 104-106 °C];1H-NMR (400 MHz,
CDCl3): d (ppm) 1.17 (t, 3H, J = 7.2 Hz), 1.31 (t, 3H, J = 7.2 Hz), 3.69–3.76 (m,
123

A novel straightforward synthesis of a-aminophosphonates:…
1H), 3.80 (s, 3H), 3.95–4.02 (m, 1H), 4.11–4.18 (m, 2H), 4.75 (d, 1H,
JHP = 24.0 Hz), 6.63 (d, 2H, J = 7.2 Hz), 6.72 (t, 1H, J = 7.6 Hz), 6.89 (d, 2H,
J = 8.4 Hz), 7.13 (t, 2H, J = 8.0 Hz), 7.42 (dd, 2H, J = 8.8 and 2.4 Hz). 13C-
NMR (100 MHz, CDCl3): d (ppm) 16.3 (d, JPC = 6.0 Hz), 16.5 (d, JPC = 6.0 Hz),
55.4 (d, JPC = 150.0 Hz), 55.2, 63.2 (d, JPC = 6.0 Hz), 63.3 (d, JPC = 6.0 Hz),
113.9, 114.0 (d, JPC = 3.0 Hz), 118.4, 127.6 (d, JPC = 3.0 Hz), 129.0 (d,
JPC = 6.0 Hz), 129.2, 146.3 (d, JPC = 15.0 Hz), 159.3 (d, JPC = 3.0 Hz).31P-
NMR (162 MHz, CDCl3/H3PO4): d (ppm) 22.89.
O,O0-Diethyl [(anilino)(4-chlorophenyl)methyl] phosphonate (4c) White solid
(65%, 230 mg); mp: 75–77 °C [Lit [47]. 73–75 °C];1H NMR (400 MHz, CDCl3):
d (ppm) 1.19 (t, 3H, J = 7.2 Hz), 1.32 (t, 3H, J = 7.2 Hz), 3.78–3.84 (m, 1H),
3.99–4.05 (m,1H), 4.09–4.21 (m, 2H), 4.78 (d, 1H, JPH = 24.0 Hz), 6.60 (d, 2H,
J = 8.0 Hz), 6.75 (t, 1H, J = 7.2 Hz), 7.14 (t, 2H, J = 8.0 Hz), 7.33 (d, 2H,
J = 8.4 Hz), 7.45 (dd, 2H, J = 7.4 and 2.4 Hz).13C NMR (100 MHz, CDCl3): d
(ppm) 16.3 (d, JPC = 5.0 Hz), 16.4 (d, JPC = 6.0 Hz), 55.80 (d, JPC = 150.0 Hz),
63.43 (d, JPC = 7.0 Hz) 63.50 (d, JPC = 7.0 Hz), 114.25, 119.07 128.85 (d,
JPC = 3.0 Hz), 129.23, 129.27, 133.82 (d, JPC = 4.0 Hz), 134.32 (d, JPC = 3.0 -
Hz), 145.75 (d, JPC = 15.0 Hz).31P NMR (162 MHz, CDCl3/H3PO4): d (ppm)
21.96.
O,O0-Diethyl [(anilino)(4-isopropylphenyl) methyl] phosphonate (4d) White solid
1
(62%, 225 mg); mp: 126–128 °C [Lit [48]. 124 °C]; H-NMR (400 MHz, CDCl3):
d (ppm) 1.12 (t, 3H, J = 7.2 Hz), 1.24 (d, 6H, J = 6.8 Hz), 1.31 (t, 3H,
J = 7.2 Hz), 2.90 (sep, 1H J = 6.8 Hz,), 3.68–3.73 (m, 1H), 3.93–3.99 (m, 1H),
4.11–4.17 (m, 2H), 4.77 (d, 1H, JPH = 24.0 Hz), 6.65 (d, 2H, J = 7.6 Hz), 6.73 (t,
1H, J = 7.6 Hz), 7.14 (t, 2H, J = 8.0 Hz), 7.21 (d, 2H, J = 8.0 Hz), 7.41 (dd, 2H,
J = 8.00 and 2.0 Hz). 13C-NMR (100 MHz, CDCl3): 16.17 (d, JPC = 6.0 Hz),
16.40 (d, JPC = 5.0 Hz), 23.96, 33.78, 55.81 (d, JPC = 150.0 Hz), 63.22 (d,
JPC = 5.0 Hz), 63.28 (d, JPC = 5.0 Hz), 113.98, 118.42, 126.70 (d, JPC = 3.0 Hz),
127.78 (d, JPC = 6.0 Hz), 129.18, 132.95, 146.30 (d, JPC = 14.0 Hz), 148.64 (d,
JPC = 4.0 Hz).31P-NMR (162 MHz, CDCl3/H3PO4): d (ppm) 22.44.
O,O0-Diethyl [(anilino)(2-methylphenyl)methyl]phosphonate (4e) [49] White solid
1
(66%, 220 mg); mp: 114–116 °C; H NMR (400 MHz, CDCl3): d (ppm) 1.08 (t,
3H, J = 7.2 Hz), 1.33 (t, 3H, J = 7.2 Hz), 2.55 (s, 3H) 3.54–3.60 (m, 1H),
3.88–3.95 (m,1H), 4.14–4.20 (m, 2H), 4.99 (d, 1H, JPH = 23.6 Hz), 6.6 (d, 2H,
J = 8.0 Hz), 6.72 (t, 1H, J = 7.2 Hz), 7.13 (t, 2H, J = 8.0 Hz), 7.18–7.25 (m, 3H),
7.55–7.60 (m, 1H). 13C NMR (100 MHz, CDCl3): d (ppm) 16.14 (d, JPC = 6.0 Hz),
16.46 (d, JPC = 6.0 Hz), 19.80 (s, 1C), 55.85 (d, JPC = 150.0 Hz), 63.16 (d,
JPC = 7.0 Hz) 63.41 (d, JPC = 7.0 Hz), 113.87, 118.61, 126.56 (d, JPC = 3.0 Hz),
127.16 (d, JPC = 4.0 Hz), 127.78, (d, JPC = 4.0 Hz), 129.24, 130.52 (d,
JPC = 3.0 Hz), 133.91 (d, JPC = 3.0 Hz), 136.40 (d, JPC = 7.0 Hz), 145.83 (d,
JPC = 15.0 Hz). 31P NMR (162 MHz, CDCl3/H3PO4): d (ppm) 23.28. Anal. Calcd
for C18H24NO3P, C, 64.83; H, 7.26; N, 4.20. Found: C, 65.05; H, 7.28; N, 4.12.
123

B. Kaboudin et al.
O,O0-Diethyl[(4-methoxyphenylamino) (phenyl) methyl] phosphonate (4f) White
1
solid (63%, 230 mg); mp: 88–90 °C [Lit [50]. colorless oil]; H NMR (400 MHz,
CDCl3): d (ppm) 1.14 (t, 3H, J = 7.2 Hz), 1.31 (t, 3H, J = 7.2 Hz), 3.68–3.74 (m,
1H), 3.72 (s, 3H), 3.93–4.99 (m,1H), 4.11–4.18 (m, 2H), 4.72 (d, 1H, JPH = 24.0 -
Hz), 6.59 (d, 2H, J = 8.8 Hz), 6.71 (d, 2H, J = 8.8 Hz), 7.27–7.31 (m, 1H),
7.33–7.37 (m, 2H); 7.49 (d, 2H, J = 7.6 Hz); 13C NMR (100 MHz, CDCl3): d
(ppm) 16.23 (d, JPC = 5.0 Hz), 16.47 (d, JPC = 5.0 Hz), 55.65, 56.54 (d,
JPC = 150.0 Hz), 63.26 (d, JPC = 5.0 Hz) 63.32 (d, JPC = 4.0 Hz), 114.73,
115.51, 127.95, 128.00, 128.60 (d, JPC = 2.0 Hz), 135.87, 140.09 (d, JPC = 17.0 -
Hz), 152.83; 31P NMR (162 MHz, CDCl3/H3PO4): d (ppm) 22.69.
O,O0-Diethyl[(4-bromophenylamino)(phenyl) methyl] phosphonate (4g) White
solid (69%, 274 mg); mp: 117–120 °C [Lit [46]. 121–123 °C]; 1H NMR
(400 MHz, CDCl3): d (ppm) 1.11 (t, 3H, J = 7.2 Hz), 1.30 (t, 3H, J = 7.2 Hz),
3.65–3.71 (m, 1H), 3.92–3.98 (m,1H), 4.10–4.20 (m, 2H), 4.69 (d, 1H,
JPH = 24.0 Hz), 6.50 (d, 2H, J = 8.8 Hz), 7.20 (d, 2H, J = 8.8 Hz), 7.29–7.38
(m, 3H), 7.46 (d, 2H, J = 7.2 Hz). 13C NMR (100 MHz, CDCl3): d (ppm) 16.19 (d,
JPC = 6.0 Hz), 16.44 (d, JPC = 6.0 Hz), 55.40 (d, JPC = 150.0 Hz), 63.32 (d,
JPC = 7.0 Hz) 63.50 (d, JPC = 7.0 Hz), 110.38 (s, 1C), 115.66 (s, 1C), 127.82 (d,
JPC = 6.0 Hz), 145.1 (d, JPC = 5.0 Hz).31P NMR (162 MHz, CDCl3/H3PO4): d
(ppm) 22.19.
O,O0-Diethyl[(4-methylphenylamino)(phenyl)methyl] phosphonate (4h) ;White
solid (70%, 233 mg); mp: 118–120 °C [Lit [51]. 117–119 °C]; 1H NMR
(400 MHz, CDCl3): d (ppm) 1.14 (t, 3H, J = 6.8 Hz), 1.31 (t, 3H, J = 6.8 Hz),
2.21 (s, 3H) 3.69–3.75 (m, 1H), 3.94–4.00 (m,1H), 4.11–4.18 (m, 2H), 4.77 (d, 1H,
JPH = 24.0 Hz), 6.55 (d, 2H, J = 8.4 Hz), 6.94 (d, 2H, J = 8.0 Hz), 7.27–7.30 (m,
1H), 7.36 (t, 2H, J = 8.0 Hz), 7.50 (d, 2H, J = 7.6 Hz);13C NMR (100 MHz,
CDCl3): d (ppm) 16.22 (d, JPC = 5.0 Hz), 16.47 (d, JPC = 6.0 Hz), 20.40, 56.49 (d,
JPC = 150.0 Hz), 63.27 (d, JPC = 4.0 Hz) 63.34 (d, JPC = 4.0 Hz), 114.20,,127.93,
127.95, 128.59, 128.61, 129.69, 135.88, 143.77 (d, JPC = 14.0 Hz); 31P NMR
(162 MHz, CDCl3/H3PO4): d (ppm) 22.73.
O,O0-Diethyl[(4-nitrophenylamino)(phenyl)methyl] phosphonate (4i) Yellow solid
1
(72%, 210 mg); mp: 148–150 °C [Lit [52]. obtained as yellow solid]; H NMR
(400 MHz, CDCl3): d (ppm) 1.12 (t, 3H, J = 7.2 Hz), 1.33 (t, 3H, J = 7.2 Hz),
3.60–3.67 (m, 1H), 3.91–3.97 (m,1H), 4.12–4.22 (m, 2H), 4.83 (d, 1H,
JPH = 24.0 Hz), 6.61 (d, 2H, J = 9.2 Hz), 7.32–7.41 (m, 3H), 7.41 (d, 2H,
J = 7.6 Hz), 8.04 (d, 2H, J = 9.2 Hz);13C NMR (100 MHz, CDCl3): d (ppm) 16.20
(d, JPC = 5.0 Hz), 16.75 (d, JPC = 6.0 Hz), 55.58(d, JPC = 150.0 Hz), 63.37 (d,
JPC = 7.0 Hz) 63.95 (d, JPC = 6.0 Hz), 112.47, 126.14, 127.73 (d, JPC = 5.0 Hz),
128.58 (d, JPC = 2.0 Hz), 128.97, (d, JPC = 1.0 Hz), 134.51 (d, JPC = 3.0 Hz),
139.09, 151.76 (d, JPC = 14 Hz); 31P NMR (162 MHz, CDCl3/H3PO4): d (ppm)
21.26.
O,O0-Diethyl [(1-naphthyl)(phenylamino) methyl] phosphonate [4j] ;White solid
(57%, 210 mg); mp: 126–127 °C [Lit [53]. 125–126 °C]. 1H NMR (400 MHz,
123

A novel straightforward synthesis of a-aminophosphonates:…
CDCl3): d (ppm) 0.76 (t, 3H, J = 7.2 Hz), 1.36 (t, 3H, J = 7.2 Hz), 3.22–3.24 (m,
1H), 3.72–3.77 (m,1H), 4.18–4.23 (m, 2H), 5.67 (d, 1H, JPH = 24.0 Hz), 6.57(d,
2H, J = 7.6 Hz), 6.68 (t, 1H, J = 7.6 Hz), 7.07 (t, 2H, J = 7.6 Hz), 7.47 (t, 1H,
J = 7.6 Hz,), 7.57 (t, 1H, J = 7.6 Hz), 7.65 (t, 1H, J = 7.6 Hz), 7.79–8.82 (m,2H),
7.93(d, 1H, J = 8.0 Hz), 8.28 (d, 1H, J = 8.0 Hz). 13C NMR (100 MHz, CDCl3): d
(ppm) 15.7 (d, JPC = 6.0 Hz), 16.5 (d, JPC = 6.0 Hz), 51.3 (d, JPC = 150.0 Hz),
63.2 (d, JPC = 7.0 Hz) 63.4 (d, JPC = 7.0 Hz), 113.6, 118.3, 122.9,
125.3125.4125.6 (d, JPC = 4.0 Hz), 126.3, 128.5(d, JPC = 4.0 Hz), 129.0, 129.2,
131.6 (d, JPC = 3.0 Hz), 131.7 (d, JPC = 4.0 Hz), 133.8 (d, JPC = 2.0 Hz), 146.1
(d, JPC = 14.0 Hz);31P NMR (162 MHz, CDCl3/H3PO4): d (ppm) 22.94.
Supporting information
Copies of 31P NMR, 1H NMR and 13C NMR for compounds 4a–4j. Supplementary
data associated with this article can be found in the online version.
Acknowledgements The authors gratefully acknowledge support by the Institute for Advanced Studies
in Basic Sciences (IASBS) Research Council (G2016IASBS31101).
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