Arabian Journal of Chemistry (2012) xxx, xxxxxx

King Saud University

Arabian Journal of Chemistry

www.ksu.edu.sa
www.sciencedirect.com

ORIGINAL ARTICLE

Solvent-free synthesis of a-aminophosphonates:

Cellulose-SO3H as an ecient catalyst
Krishnammagari Suresh Kumar a, Balam Satheesh Krishna a,
Chinnapareddy Bhupendra Reddy a, Mudumala Veera Narayana Reddy b,
Cirandur Suresh Reddy a,*
a
b

Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India

Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of Korea

Received 24 December 2011; accepted 15 September 2012

KEYWORDS
Cellulose-SO3H;
Kabachnik-Fields reaction;
CP bond formation;
a-Aminophosphonates

Abstract a-Aminophosphonates possess a broad range of applications ranging from agrochemistry to medicine. We developed an efcient and eco-friendly Cellulose-SO3H catalyzed one-pot synthesis of a-aminophosphonates by three-component, room temperature reaction of an aldehyde, an
amine and dialkylphosphite under solvent-free conditions. The major advantages of the present
method are simple experimentation, use of inexpensive and eco-friendly reusable catalyst with good
yields and short reaction times.
2012 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

1. Introduction
a-Aminophosphonates are phosphorus structural analogs of aamino acids (Sheridan, 2002). The medicinal importance and
biological effects of a-aminophosphonate derivatives as antibiotics (Atherton et al., 1986), herbicides, fungicides, insecticides
(Maier and Spoerri, 1991), enzyme inhibitors (Allen et al.,
1989), HIV protease (Peyman et al., 1994), plant growth regulators (Emsley and Hall, 1976) anti-thrombotic agents (Meyer
and Barlett, 1998), peptidases and proteases (Miller et al.,
1998), had stimulated scientic research to develop many
* Corresponding author. Tel.: +91 9849694958; fax: +91 877
2289555.
E-mail address: csrsvu@gmail.com (C.S. Reddy).
Peer review under responsibility of King Saud University.

Production and hosting by Elsevier

synthetic procedures for them. Based on this background over

the last few years we have synthesized and reported (Prasad
et al., 2007; Reddy et al., 2010) some bioactive, antimicrobial,
anti cancer and anti oxidant phosphonates.
Among the various synthetic protocols described for the
synthesis of a-aminophosphonates (Ordonez et al., 2009)
nucleophilic addition of phosphites to imines i.e., Kabachnik-Fields reaction (Cherkasov and Galkin, 1998) proved to
be a convenient route. For the efcient and capitulate oriented
synthesis of a-aminophosphonates various other synthetic
methodologies have been reported by using different catalysts.
In such hierarchical reports Lewis acids such as lantanide triate, (Manabe and Kobayashi, 2000) samarium diiodide,
(Xu et al., 2003) indium (III) chloride, Lee et al., 2001 (bromodimethyl) sulfonium bromide, (Kudrimoti and Bommena,
2005) lithium perchlorate (Heydari et al., 2001), zirconium
tetrachloride (Yadav et al., 2001), tin tetrachloride (Laschat
and Kunz, 1992), bismuth nitrate pentahydrate (Bhattacharya
and Kaur, 2007) and magnesium perchlorate (Bhagat and

1878-5352 2012 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.arabjc.2012.09.009

Please cite this article in press as: Kumar, K.S. et al., Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an
ecient catalyst. Arabian Journal of Chemistry (2012), http://dx.doi.org/10.1016/j.arabjc.2012.09.009

K.S. Kumar et al.

Chakraborti, 2007) were identied as efcient catalysts. Several metal complexes have also been used as effective catalysts
for this reaction, (De Noronha et al., 2011) including ytterbium, boron, aluminium, zirconium and molybdenum complexes. As an alternative, the use of heteropoly acid (HPA)
such as 12-tungstophosphoric acid as catalysts has also received considerable attention (Heydari et al., 2007). In yet another attempt phenyltrimethylammonium chloride (Heydari
and Are, 2007) was used as a catalyst for obtaining new generation of a-aminophosphonates. The same applicability is not
excluded for the natural phosphate alone or potassium uoride
doped natural phosphate (Zahouily et al., 2007). Recently, the
organocatalysis has emerged as an important area of research
over the last decade as it involved more stable, eco-friendly,
readily available, less expensive catalyst and required less
demanding reaction conditions in comparison to the metal catalyst. (Dalko and Moisan, 2001) In such sequence oxalic acid,
(Vahdat et al., 2008) quinine, (Pettersen et al., 2006) and camphor sulfonic acid (Shinde et al., 2011) were used as potential
catalysts. Similarly some solid supported catalysts (Chandrasekhar et al., 2001) like silica supported tantalum pentachloride
and alumina-supported reagents were also exploited for
accomplishing the same results. Later on Lewis salt boron triuoride diethyl etherate, transition metal oxide titanium dioxide and some resins like amberlite-IR 120 and amberlyst-15
were explored as catalysts in the synthesis of a-aminophosphonates (Bhattacharya and Rana, 2008). Recently, the solid acid
catalyst like montmorillonite KSF and sulfamic acid was employed for this purpose (Mitragotri et al., 2008).
However, these catalysts have various drawbacks like their
non availability difculties in preparation and requirement of
long reaction times. Many of them when used with substrates
containing aliphatic amino groups, uncharacterizable by products were formed. Due to signicant potential biological activity of a-aminophosphonates the emphasis was focused on the
development of an efcient and at the same time bio-friendly
sustainable synthesis for them. In this context the search for
efcient and green catalyst arose. Efforts in this direction led
to the discovery of Cellulose-SO3H that was already proved
as promising solid acid catalyst for the synthesis of some important class of organic compounds (Shaabani et al., 2008) like
a-amino nitriles, quinolines and imidazoazines. In this connection, now we wish to report the Cellulose-SO3H as an efcient
catalyst for the synthesis of a-aminophosphonates from an

Table 1

aldehyde, an amine and dialkylphosphite in one pot solvent free

three component synthesis at room temperature.
2. Experimental
2.1. Materials
Chemicals were procured from SigmaAldrich and Merck and
used as such without further purication. All solvents used for
the spectroscopic and other physical studies were reagent grade
and further puried by literature methods (Armarego and
Perrin, 1997).
2.2. Characterization techniques
The melting points (mp) were determined in open capillary
tubes on a Mel-Temp apparatus (Tempo Instruments and
Equip Pvt. Ltd., Mumbai, India), expressed in degrees centigrade (C) and are uncorrected. Infrared (IR) Spectra were obtained on a Nicolet (San Diego, CA, USA) 380 Fourier
transform infrared (FT-IR) spectrophotometer at the Environmental Engineering Laboratory, Sri Venkateswara University,
Tirupati, India and samples were analyzed as potassium bromide (KBr) disks and absorptions (mmax) were reported in wave
numbers (cm1). All the compounds were dissolved in CDCl3
for 1H, 13C and DMSO-d6 for 31P NMR spectra were recorded
on a Bruker (Ettlingen, Germany) AMX 400 MHz nuclear
magnetic resonance (NMR) spectrometer operating at
400 MHz for 1H NMR, 100.57 MHz for 13C NMR, and
161.9 MHz for 31P NMR respectively. The chemical shifts
were expressed in delta (d) and were referenced to TMS in
1
H NMR and 13C NMR and 85% H3PO4 in 31P NMR. Mass
spectra were recorded on a QTof mass spectrometer (QSTAR
XL, Applied Biosystems/MDS Sciex, USA). Microanalysis
was performed on a Thermo Finnigan (Courtaboeuf, France)
Flash EA 1112 I instrument at the University of Hyderabad,
Hyderabad, India.
2.3. General procedure for the synthesis of a-aminophosphonates
(4aw)
A mixture of an aldehyde (1 mmole), an amine (1 mmole),
diethylphosphite (1 mmole) and Cellulose-SO3H (0.04 g) were

Optimization of the synthesis of a-aminophosphonates.a

Entry

Catalyst (mol%)

Time (min)

Yieldb

1
2
3
4
5
6
7
8

Catalyst free
Sulfamic acid (10)
Silica-sulfuric acid (10)
p-Toluenesulfonic acid (10)
Cellulose-SO3H (0.04)c
Camphorsulfonic acid (10)
Starch-SO3H (0.04)c
b-Cyclodextrin (10)

10 (h)
40
5 (h)
40
15
30
30
6 (h)

50
59
87d
72
98
91
87
55e

Reaction condition: Benzaldehyde (1 mmol), Aniline (1 mmol) and diethylphosphite (1 mmol) at room temperature under solvent free
condition.
b
Isolated yield.
c
Amount maintain in grams
d
Acetonitrile used as solvent.
e
Water used as solvent under reuxing condition.

Please cite this article in press as: Kumar, K.S. et al., Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an
ecient catalyst. Arabian Journal of Chemistry (2012), http://dx.doi.org/10.1016/j.arabjc.2012.09.009

Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an efcient catalyst

stirred at room temperature for a particular period of time as
given in Table 2 to produce the title compounds (Scheme 1).
After completion of the reaction dichloromethane was added
to the reaction mixture and stirred and then separated the Cellulose-SO3H and collected by ltration. Dichloromethane
layer was removed in a rota-evaporator. The residual product
was puried by silica gel column chromatography. The
collected Cellulose-SO3H was reused for at least 3 to 4 runs
without loss of product yield.
2.4. General procedure for the synthesis of Cellulose-SO3H
catalyst (Kumar et al., 2010)
To a magnetically stirred solution of cellulose (5.00 g) in
dichloromethane (20 mL), chlorosulfonic acid (1.00 g) was
added drop wise during 2 h. After the addition the mixture
was stirred for another 2 h. The white solid thus separated
was ltered and washed with acetonitrile (30 mL) and dried
at room temperature. The yield was 5.6 g.
2.5. Physical and spectral data of the products (4aw)
2.5.1. Diethylphenyl(phenylamino)methylphosphonate (4a)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.46
7.45 (m, 2H, Ar-H), 7.317.29 (m, 3H, Ar-H), 7.087.07 (m,
2H, Ar-H), 6.696.58 (m, 3H, Ar-H), 4.894.87 (m, 1H,
NH), 4.804.72 (m, 1H, CHP), 4.124.10 (m, 2H, OCH2CH3),
3.923.90 (m, 1H, OCH2CH3), 3.673.66 (m, 1H, OCH2CH3),
1.27 (t, 3H, J = 7.0 Hz, OCH2CH3), 1.10 (t, 3H, J = 7.0 Hz,
OCH2CH3); 13C NMR (100.57 MHz, TMS, CDCl3): d 147.5
(C-10 ), 136.2 (C-1), 129.6 (C-30 & C-50 ), 128.5 (C-3 & C-5),
128.1 (C-2 & C-6), 126.7 (C-4), 120.6 (C-40 ), 113.5 (C-20 &

Synthesis of a-aminophosphonates 4a.a

Table 2
Entry

Solvent

Time (min)

Yield (%)c

1
2
3
4
5
6
7
8
9
10

EtOH
CH2Cl2
CH3CN
Toluene
Solvent-free
EtOH + Cellulose-SO3Hb
CH2Cl2 + Cellulose-SO3H
CH3CN + Cellulose-SO3H
Toluene + Cellulose-SO3H
Solvent-free + Cellulose-SO3H

120
120
120
120
60
60
60
60
60
15

nrd
nr
nr
nr
nr
66
70
71
75
98

Reaction conditions: room temperature, equimolar (1 mmol)

ratio.
b
Amount of catalyst (Cellulose-SO3H) used in 0.04 g.
c
Isolated yield calculated after purication.
d
No reaction.

O
O

O
R1

+ R2

Scheme 1
phonates.

NH 2 +
2

Cellulose-SO3H
Neat ,r.t.,15-30 min

OEt One pot, 83-98%

OEt
3

R1
H

P(OE t)2
NH R 2

C-60 ), 69.6 (d, J = 151.5 Hz, P-CH), 62.3 (d, J = 6.3 Hz,
OCH2CH3), 16.3 (d, J = 6.9 Hz, OCH2CH3).
2.5.2. Diethylphenyl(4-chlorophenylamino)methylphosphonate
(4b)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.48
6.51 (m, 9H, Ar-H), 4.854.82 (m, 1H, NH), 4.794.71 (m,
1H, CHP), 4.104.07 (m, 2H, OCH2CH3), 3.943.91 (m, 1H,
OCH2CH3), 3.653.62 (m, 1H, OCH2CH3), 1.26 (t, 3H,
J = 6.9 Hz, OCH2CH3), 1.09 (t, 3H, J = 6.9 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 145.7 (C-10 ), 136.2
(C-1), 129.6 (C-30 & C-50 ), 128.6 (C-3 & C-5), 128.3 (C-2 &
C-6), 126.7 (C-4), 126.1 (C-40 ), 114.7 (C-20 & C-60 ), 69.5 (d,
J = 150.8 Hz, P-CH), 62.5 (d, J = 6.0 Hz, OCH2CH3), 16.3
(d, J = 5.9 Hz, OCH2CH3).
2.5.3. Diethylphenyl(2-chlorophenylamino)methylphosphonate
(4c)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.56
6.79 (m, 9H, Ar-H), 4.864.82 (m, 1H, NH), 4.784.71 (m,
1H, CHP), 4.114.06 (m, 2H, OCH2CH3), 3.943.91 (m, 1H,
OCH2CH3), 3.663.63 (m, 1H, OCH2CH3), 1.25 (t, 3H,
J = 7.0 Hz, OCH2CH3), 1.08 (t, 3H, J = 7.0 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 143.9 (C-10 ), 136.1
(C-1), 130.8 (C-50 ), 128.5 (C-3 & C-5), 128.3 (C-2 & C-6),
127.6 (C-30 ), 126.7 (C-4), 123.8 (C-40 ), 122.4 (C-60 ), 114.9 (C20 ), 69.4 (d, J = 152.1 Hz, P-CH), 62.2 (d, J = 6.3 Hz,
OCH2CH3), 16.3 (d, J = 6.2 Hz, OCH2CH3).
2.5.4. Diethyl (4-methoxyphenylamino)(phenyl)
methylphosphonate (4d)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.45 (d,
2H, J = 7.3 Hz, Ar-H), 7.327.30 (m, 3H, Ar-H), 6.69 (d, 2H,
J = 9.2 Hz, Ar-H), 6.55 (d, 2H, J = 9.2 Hz, Ar-H), 4.68 (d,
1H, J = 24.3 Hz, CHP), 4.56 (brs, 1H, NH), 4.144.08 (m,
2H, OCH2CH3), 3.933.91 (m, 1H, OCH2CH3), 3.723.70
(m, 1H, OCH2CH3), 3.68 (s, 3H, Ar-OCH3), 1.28 (t, 3H,
J = 7.1 Hz, OCH2CH3), 1.11 (t, 3H, J = 7.1 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 151.9 (C-40 ), 140.2
(C-10 ), 136.3 (C-1), 128.7 (C-3 & C-5), 128.3 (C-2 & C-6),
126.6 (C-4), 115.8 (C-20 & C-60 ), 115.3 (C-30 & C-50 ), 69.9 (d,
J = 151.4 Hz, P-CH), 62.2 (d, J = 6.5 Hz, OCH2CH3), 55.8
(Ar-OCH3), 16.2 (d, J = 6.3 Hz, OCH2CH3).
2.5.5. Diethyl (4-uorophenylamino)(phenyl)
methylphosphonate (4e)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.46
6.52 (m, 9H, Ar-H), 4.874.85 (m, 1H, NH), 4.734.66 (m,
1H, CHP), 4.144.10 (m, 2H, OCH2CH3), 3.933.91 (m, 1H,
OCH2CH3), 3.683.66 (m, 1H, OCH2CH3), 1.28 (t, 3H,
J = 7.0 Hz, OCH2CH3), 1.10 (t, 3H, J = 7.0 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 155.6 (C-40 ), 143.2
(C-10 ), 136.3 (C-1), 128.7 (C-3 & C-5), 128.3 (C-2 & C-6),
126.7 (C-4), 118.7 (C-20 & C-60 ), 116.5 (C-30 & C-50 ), 69.7 (d,
J = 151.5 Hz, P-CH), 62.3 (d, J = 6.9 Hz, OCH2CH3), 16.3
(d, J = 6.1 Hz, OCH2CH3).

4a-w

Cellulose-SO3H catalyzed synthesis of a-aminophos-

2.5.6. Diethyl (benzylamino)(phenyl)methylphosphonate (4f)

viscous colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d
7.427.26 (m, 10H, Ar-H), 4.084.04 (m, 2H, OCH2CH3), 3.99

Please cite this article in press as: Kumar, K.S. et al., Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an
ecient catalyst. Arabian Journal of Chemistry (2012), http://dx.doi.org/10.1016/j.arabjc.2012.09.009

4
(m, 1H, NH), 3.823.79 (m, 2H, OCH2CH3), 3.53 (d, 1H,
J = 23.2 Hz, CHP), 2.63 (s, 2H, Ar-CH2-N), 1.28 (t, 3H,
J = 7.0 Hz, OCH2CH3), 1.12 (t, 3H, J = 7.0 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 140.2 (C-10 ), 130.7
(C-1), 129.2 (C-2 & C-6), 128.8 (C-30 & C-50 ), 128.3 (C-3 &
C-5), 127.9 (C-20 & C-60 ), 127.3 (C-40 ), 127.0 (C-4), 66.3 (d,
J = 152.2 Hz, P-CH), 62.2 (d, J = 6.3 Hz, OCH2CH3), 53.1
(Ar-CH2-N), 16.3 (d, J = 5.9 Hz, OCH2CH3).
2.5.7. Diethyl(4-chlorophenyl)(phenylamino)
methylphosphonate (4g)
Yellow semi solid; 1H NMR (400 MHz, TMS, CDCl3): d 7.42
(d, 2H, J = 8.0 Hz, Ar-H), 7.30 (d, 2H, J = 8.0, Ar-H), 7.10
6.60 (m, 5H, Ar-H), 5.90 (brs, 1H, NH), 4.77 (d, 1H,
J = 24.4 Hz, CHP), 4.174.09 (m, 2H, OCH2CH3), 3.843.77
(m, 1H, OCH2CH3), 3.763.71 (m, 1H, OCH2CH3), 1.28 (t,
3H, J = 6.9 Hz, OCH2CH3), 1.16 (t, 3H, J = 6.9 Hz,
OCH2CH3); 13C NMR (100.57 MHz, TMS, CDCl3): d 147.3
(C-10 ), 134.4 (C-1), 132.5 (C-4), 129.5 (C-30 & C-50 ), 128.6
(C-3 & C-5), 128.2 (C-2 & C-6), 120.8 (C-40 ), 113.5 (C-20 &
C-60 ), 69.2 (d, J = 151.5 Hz, P-CH), 62.8 (d, J = 6.4 Hz,
OCH2CH3), 16.8 (d, J = 6.0 Hz, OCH2CH3).
2.5.8. Diethyl(4-chlorophenyl)(4-methoxyphenylamino)methyl
phosphonate (4h)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.39
7.29 (m, 4H, Ar-H), 6.706.50 (m, 4H, Ar-H), 4.704.62 (m,
1H, CHP), 4.534.51 (m, 1H, NH), 4.144.09 (m, 2H,
OCH2CH3), 4.033.94 (m, 1H, OCH2CH3), 3.813.80 (m,
1H, OCH2CH3), 3.69 (s, 3H, Ar-OCH3), 1.29 (t, 3H,
J = 7.0 Hz, OCH2CH3), 1.16 (t, 3H, J = 7.0 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 151.8 (C-40 ), 139.9
(C-10 ), 134.2 (C-1), 132.8 (C-4), 128.8 (C-3 & C-5), 128.3
(C-2 & C-6), 115.9 (C-20 & C-60 ), 114.8 (C-30 & C-50 ), 69.9
(d, J = 151.6 Hz, P-CH), 62.8 (d, J = 5.8 Hz, OCH2CH3),
55.7 (Ar-OCH3), 16.4 (d, J = 5.9 Hz, OCH2CH3).

K.S. Kumar et al.

(t, 3H, J = 6.9 Hz, OCH2CH3); 13C NMR (100.57 MHz,
TMS, CDCl3): d 147.8 (C-10 ), 145.8 (C-4), 142.5 (C-1), 129.8
(C-30 & C-50 ), 127.9 (C-2 & C-6), 123.6 (C-3 & C-5), 120.8
(C-40 ), 113.5 (C-20 & C-60 ), 69.5 (d, J = 151.5 Hz, P-CH),
62.5 (d, J = 6.3 Hz, OCH2CH3), 16.8 (d, J = 6.1 Hz,
OCH2CH3OCH2CH3).
2.5.11. Diethyl(phenylamino)(p-tolyl)methylphosphonate (4k)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.35
6.66 (m, 7H, Ar-H), 6.60 (d, 2H, J = 7.5 Hz, Ar-H), 4.75
(brs, 1H, NH), 4.71 (d, 1H, J = 24.0 Hz, CHP), 4.144.08
(m, 2H, OCH2CH3), 3.953.92 (m, 1H, OCH2CH3), 3.70
3.68 (m, 1H, OCH2CH3), 2.30 (s, 3H, Ar-CH3), 1.28 (t, 3H,
J = 7.0 Hz, OCH2CH3), 1.13 (t, 3H, J = 7. 0 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 147.8 (C-10 ), 136.8
(C-4), 133.3 (C-1), 129.8 (C-30 & C-50 ), 128.9 (C-3 & C-5),
126.5 (C-2 & C-6), 120.8 (C-40 ), 113.8 (C-20 & C-60 ), 70.2 (d,
J = 150.5 Hz, P-CH), 62.6 (d, J = 6.3 Hz, OCH2CH3), 21.4
(Ar-CH3), 16.7 (d, J = 6.9 Hz, OCH2CH3).
2.5.12. Diethyl(4-methoxyphenylamino)(p-tolyl)
methylphosphonate (4l)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.34 (d,
2H, J = 7.8 Hz, Ar-H), 7.12 (d, 2H, J = 7.8 Hz, Ar-H), 6.68
(d, 2H, J = 8.2 Hz, Ar-H), 6.55 (d, 2H, J = 8.2 Hz, Ar-H),
4.80 (brs, 1H, NH), 4.66 (d, 1H, J = 24.3 Hz, CHP), 4.14
4.09 (m, 2H, OCH2CH3), 3.953.92 (m, 1H, OCH2CH3),
3.713.69 (m, 1H, OCH2CH3), 3.67 (s, 3H, Ar-OCH3), 2.30
(s, 3H, Ar-CH3), 1.28 (t, 3H, J = 7.0 Hz, OCH2CH3), 1.14
(t, 3H, J = 7.0 Hz, OCH2CH3); 13C NMR (100.57 MHz,
TMS, CDCl3): d 151.7 (C-40 ), 139.7 (C-10 ), 136.8 (C-4), 132.7
(C-1), 128.3 (C-3 & C-5), 126.5 (C-2 & C-6), 115.9 (C-20 &
C-60 ), 114.8 (C-30 & C-50 ), 69.2 (d, J = 151.5 Hz, P-CH),
62.2 (d, J = 6.8 Hz, OCH2CH3), 55.9 (Ar-OCH3), 21.3 (ArCH3), 16.3 (d, J = 6.5 Hz, OCH2CH3).
2.5.13. Diethyl(benzylamino)(p-tolyl)methylphosphonate (4m)

2.5.9. Diethyl(3-chlorophenyl)(phenylamino)
methylphosphonate (4i)
White solid, mp 9092 C; 1H NMR (400 MHz, TMS, CDCl3):
d 7.50 (s, 1H, Ar-H), 7.39 (d, 1H, J = 7.5 Hz, Ar-H), 7.297.22
(m, 2H, Ar-H), 7.12 (t, 2H, J = 8.0 Hz, Ar-H), 6.72 (t, 1H,
J = 7.2 Hz, Ar-H), 6.59 (d, 2H, J = 7.7 Hz, Ar-H), 5.55 (brs,
1H, NH), 4.76 (d, 1H, J = 24.5 Hz, CHP), 4.184.11 (m, 2H,
OCH2CH3), 3.983.88 (m, 1H, OCH2CH3), 3.81 3.79 (m,
1H, OCH2CH3), 1.29 (t, 3H, J = 7.2 Hz, OCH2CH3), 1.22 (t,
3H, J = 7.2 Hz, OCH2CH3); 13C NMR (100.57 MHz, TMS,
CDCl3): d 147.6 (C-10 ), 137.5 (C-1), 134.3 (C-3), 130.2 (C-5),
129.8 (C-30 & C-50 ), 126.9 (C-4), 126.3 (C-2), 126.1 (C-6),
120.8 (C-40 ), 113.8 (C-20 & C-60 ), 69.4 (d, J = 150.9 Hz,
P-CH), 62.3 (d, J = 6.3 Hz, OCH2CH3), 16.1 (d,
J = 6.2 Hz, OCH2CH3).
2.5.10. Diethyl(4-nitrophenyl)(phenylamino)
methylphosphonate (4j)
Bright yellow solid, mp 122124 C; 1H NMR (400 MHz,
TMS, CDCl3): d 8.13 (d, 2H, J = 8.5 Hz, Ar-H), 7.66 (d,
2H, J = 8.5 Hz, Ar-H), 7.066.55 (m, 5H, Ar-H), 5.21 (brs,
1H, NH), 4.90 (d, 1H, J = 25.2 Hz, CHP), 4.173.86 (m,
4H, OCH2CH3), 1.26 (t, 3H, J = 6.9 Hz, OCH2CH3), 1.16

Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.33 (d,

2H, J = 7.8 Hz, Ar-H), 7.12 (d, 2H, J = 7.8 Hz, Ar-H), 6.80
6.70 (m, 5H, Ar-H), 4.854.83 (m, 1H, NH), 4.704.63 (m, 1H,
CHP), 4.144.10 (m, 2H, OCH2CH3), 3.923.91 (m, 1H,
OCH2CH3), 3.793.67 (m, 3H, OCH2CH3 & Ar-CH2-N),
2.31 (s, 3H, Ar-CH3), 1.28 (t, 3H, J = 7.1 Hz, OCH2CH3),
1.12 (t, 3H, J = 7.1 Hz, OCH2CH3); 13C NMR
(100.57 MHz, TMS, CDCl3): d 140.3 (C-10 ), 136.9 (C-4),
128.8 (C-3 & C-5), 128.3 (C-30 & C-50 ), 127.9 (C-1), 127.7
(C-20 & C-60 ), 127.5 (C-2 & C-6), 126.8 (C-40 ), 66.5 (d,
J = 151.5 Hz, P-CH), 62.8 (d, J = 6.9 Hz, OCH2CH3), 50.1
(Ar-CH2-N), 21.7 (Ar-CH3), 16.6 (d, J = 6.4 Hz, OCH2
CH3).
2.5.14. Diethyl(4-methoxyphenyl)(phenylamino)
methylphosphonate (4n)
Viscous colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d
7.33 (d, 2H, J = 8.5 Hz, Ar-H), 7.02 (d, 2H, J = 8.5 Hz, ArH), 6.776.52 (m, 5H, Ar-H), 5.20 (brs, 1H, NH), 4.63 (d,
1H, J = 23.7 Hz, CHP), 4.073.61 (m, 4H, OCH2CH3), 3.69
(s, 3H, Ar-OCH3), 1.21 (t, 3H, J = 6.9 Hz, OCH2CH3), 1.04
(t, 3H, J = 6.9 Hz, OCH2CH3); 13C NMR (100.57 MHz,
TMS, CDCl3): d 158.6 (C-4), 147.6 (C-10 ), 129.3 (C-30 &

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Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an efcient catalyst

C-50 ), 128.4 (C-1), 127.5 (C-2 & C-6), 120.7 (C-40 ), 114.3 (C-3
& C-5), 113.3 (C-20 & C-60 ), 69.5 (d, J = 151.6 Hz, P-CH), 62.5
(d, J = 7.0 Hz, OCH2CH3), 55.9 (Ar-OCH3), 16.3 (d,
J = 6.9 Hz, OCH2CH3).
2.5.15. Diethyl(4-methoxyphenyl)(4-nitrophenylamino)methyl
phosphonate (4o)
Yellow solid, mp 112114 C; 1H NMR (400 MHz, TMS,
CDCl3): d 7.96 (d, 2H, J = 9.1 Hz, Ar-H), 7.13 (d, 2H,
J = 8.5 Hz, Ar-H), 6.65 (brs, 1H, NH), 6.55 (d, 2H,
J = 8.5 Hz, Ar-H), 6.38 (d, 2H, J = 9.1 Hz, Ar-H), 4.55 (d,
1H, J = 23.7 Hz, CHP), 3.903.81 (m, 4H, OCH2CH3), 3.42
(s, 3H, Ar-OCH3), 0.97 (t, 3H, J = 7.1 Hz, OCH2CH3), 0.89
(t, 3H, J = 7.1 Hz, OCH2CH3); 13C NMR (100.57 MHz,
TMS, CDCl3): d 158.8 (C-4), 153.5 (C-10 ), 136.1 (C-40 ), 128.2
(C-1), 127.9 (C-2 & C-6), 127.2 (C-30 & C-50 ), 114.5 (C-20 &
C-60 ), 114.3 (C-3 & C-5), 69.7 (d, J = 151.5 Hz, P-CH), 55.7
(Ar-OCH3), 62.3 (d, J = 6.3 Hz, OCH2CH3), 16.1 (d,
J = 6.0 Hz, OCH2CH3).
2.5.16. Diethyl(4-methoxyphenyl)(3-nitrophenylamino)methyl
phosphonate (4p)
Yellow solid, mp 149151 C; 1H NMR (400 MHz, TMS,
CDCl3): d 7.65 (s, 1H, Ar-H), 7.45 (d, 2H, J = 8.5 Hz, ArH), 7.347.17 (m, 2H, Ar-H), 7.09 (t, 1H, J = 6.7 Hz, ArH), 6.87 (d, 2H, J = 8.2 Hz, Ar-H), 5.60 (brs, 1H, NH), 5.11
(d, 1H, J = 23.1 Hz, CHP), 4.053.99 (m, 2H, OCH2CH3),
3.903.86 (m, 1H, OCH2CH3), 3.773.73 (m, 1H, OCH2CH3),
3.68 (s, 3H, Ar-OCH3), 1.15 (t, 3H, J = 7.0 Hz, OCH2CH3),
1.04 (t, 3H, J = 7.0 Hz, OCH2CH3); 13C NMR
(100.57 MHz, TMS, CDCl3): d 158.8 (C-4), 148.5 (C-30 ),
148.1 (C-10 ), 130.8 (C-50 ), 128.7 (C-1), 127.7 (C-2 & C-6),
119.8 (C-60 ), 114.7 (C-3 & C-5), 112.5 (C-40 ), 106.8 (C-20 ),
69.3 (d, J = 151.1 Hz, P-CH), 62.2 (d, J = 6.8 Hz, OCH2
CH3), 55.6 (Ar-OCH3), 16.4 (d, J = 6.2 Hz, OCH2CH3).
2.5.17. Diethyl(4-uorophenylamino)(4-methoxyphenyl)methyl
phosphonate (4q)
White solid, mp 5254 C; 1H NMR (400 MHz, TMS, CDCl3):
d 7.34 (d, 2H, J = 8.3 Hz, Ar-H), 6.82 (d, 2H, J = 8.3 Hz, ArH), 6.76 (d, 2H, J = 8.8 Hz, Ar-H), 6.51 (d, 2H, J = 8.8 Hz,
Ar-H), 5.70 (brs, 1H, NH), 4.724.63 (m, 1H, CHP), 4.10
4.03 (m, 2H, OCH2CH3), 3.903.70 (m, 1H, OCH2CH3),
3.68 (s, 3H, Ar-OCH3), 3.643.63 (m, 1H, OCH2CH3), 1.22
(t, 3H, J = 7.0 Hz, OCH2CH3), 1.07 (t, 3H, J = 7.0 Hz,
OCH2CH3); 13C NMR (100.57 MHz, TMS, CDCl3): d 158.7
(C-4), 155.9 (C-40 ), 143.4 (C-10 ), 128.6 (C-1), 127.7 (C-2 &
C-6), 118.6 (C-20 & C-60 ), 116.6 (C-30 & C-50 ), 114.3 (C-3 &
C-5), 69.7 (d, J = 151.5 Hz, P-CH), 62.5 (d, J = 6.7 Hz,
OCH2CH3), 55.9 (Ar-OCH3), 16.5 (d, J = 6.2 Hz, OCH2
CH3).
2.5.18. Diethyl(4-methoxyphenyl)(4-methoxyphenylamino)
methyl phosphonate (4r)
White solid, mp 118120 C; 1H NMR (400 MHz, TMS,
CDCl3): d 7.20 (d, 2H, J = 8.5 Hz, Ar-H), 6.96 (d, 2H,
J = 8.5 Hz, Ar-H), 6.67 (d, 2H, J = 7.2 Hz, Ar-H), 6.51 (d,
2H, J = 7.2 Hz, Ar-H), 5.45 (brs, 1H, NH), 4.62 (d, 1H,
J = 24.2 Hz, CHP), 4.124.03 (m, 2H, OCH2CH3), 3.923.87
(m, 1H, OCH2CH3), 3.703.62 (m, 1H, OCH2CH3), 3.45 (s,

3H, Ar-OCH3), 3.40 (s, 3H, Ar-OCH3), 1.27 (t, 3H,

J = 7.0 Hz, OCH2CH3), 1.09 (t, 3H, J = 7.0 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 158.8 (C-4), 151.3
(C-40 ), 140.3 (C-10 ), 128.7 (C-1), 128.1 (C-2 & C-6), 115.9 (C20 & C-60 ), 114.8 (C-30 & C-50 ), 113.8 (C-3 & C-5), 69.7 (d,
J = 151.5 Hz, P-CH), 62.3 (d, J = 6.3 Hz, OCH2CH3), 55.6
(Ar-OCH3), 55.2 (Ar-OCH3), 16.5 (d, J = 6.9 Hz, OCH2
CH3).
2.5.19. Diethyl (4-nitrophenylamino)(3,4,5-trimethoxyphenyl)
methylphosphonate (4s)
White solid, mp 9092 C; 1H NMR (400 MHz, TMS, CDCl3):
d 7.12 (d, 2H, J = 7.3 Hz, Ar-H), 7.07 (d, 2H, J = 7.3 Hz, ArH), 6.83 (s, 2H, Ar-H), 5.42 (brs, 1H, NH), 4.63 (d, 1H,
J = 24.2 Hz, CHP), 4.114.04 (m, 2H, OCH2CH3), 3.913.89
(m, 1H, OCH2CH3), 3.713.62 (m, 1H, OCH2CH3), 3.51 (s,
3H, Ar-OCH3), 3.47 (s, 6H, Ar-OCH3), 1.26 (t, 3H,
J = 7.0 Hz, OCH2CH3), 1.10 (t, 3H, J = 7.0 Hz, OCH2CH3);
13
C NMR (100.57 MHz, TMS, CDCl3): d 152.6 (C-3 & C-5),
151.5 (C-40 ), 139.7 (C-10 ), 137.5 (C-4), 130.6 (C-1), 115.9 (C20 & C-60 ), 114.8 (C-30 & C-50 ), 104.2 (C-2 & C-6), 70.7 (d,
J = 151.5 Hz, P-CH), 62.5 (d, J = 6.9 Hz, OCH2CH3), 56.1
(Ar-OCH3), 55.8 (Ar-OCH3), 16.1 (d, J = 6.7 Hz, OCH2
CH3).
2.5.20. Diethyl(phenylamino)(3,4,5-trimethoxyphenyl)methyl
phosphonate (4t)
White solid, mp 109111 C; 1H NMR (400 MHz, TMS,
CDCl3): d 7.107.03 (m, 3H, Ar-H), 6.816.75 (m, 4H, ArH), 5.41 (brs, 1H, NH), 4.62 (d, 1H, J = 24.2 Hz, CHP),
4.104.03 (m, 2H, OCH2CH3), 3.923.88 (m, 1H, OCH2CH3),
3.723.63 (m, 1H, OCH2CH3), 3.49 (s, 3H, Ar-OCH3), 3.49 (s,
6H, Ar-OCH3), 1.25 (t, 3H, J = 7.1 Hz, OCH2CH3), 1.12 (t,
3H, J = 7.1 Hz, OCH2CH3); 13C NMR (100.57 MHz, TMS,
CDCl3): d 152.5 (C-3 & C-5), 140.2 (C-10 ), 137.3 (C-4), 128.3
(C-30 & C-50 ), 127.6 (C-20 & C-60 ), 126.9 (C-40 ), 125.4 (C-1),
105.6 (C-2 & C-6), 67.3 (d, J = 150.8 Hz, P-CH), 62.5 (d,
J = 7.0 Hz, OCH2CH3), 60.8 (Ar-OCH3), 56.1 (Ar-OCH3),
16.4 (d, J = 6.3 Hz, OCH2CH3OCH2CH3).
2.5.21. Diethyl (phenylamino)(furan-2-yl)methylphosphonate
(4u)
Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.54
7.49 (m, 1H, Ar-H), 7.477.42 (m, 1H, Ar-H), 7.287.23 (m,
1H, Ar-H), 7.117.07 (m, 1H, Ar-H), 6.996.78 (m, 4H, ArH), 5.72 (brs, 1H, NH), 4.084.02 (m, 2H, OCH2CH3), 3.91
3.73 (m, 1H, OCH2CH3), 3.69 (s, 3H, Ar-OCH3), 3.653.61
(m, 1H, OCH2CH3), 1.21 (t, 3H, J = 7.0 Hz, OCH2CH3),
1.06 (t, 3H, J = 7.0 Hz, OCH2CH3); 13C NMR
(100.57 MHz, TMS, CDCl3): d 159.5 (C-2), 145.9 (C-10 ),
142.3 (C-5), 129.8 (C-30 & C-50 ), 127.3 (C-6), 114.8 (C-20 &
C-60 ), 111.2 (C-4), 107.2 (C-3), 63.3 (d, J = 151.5 Hz, P-CH),
62.1 (d, J = 6.3 Hz, OCH2CH3), 16.5 (d, J = 6.1 Hz,
OCH2CH3).
2.5.22. Diethyl(3-nitrophenylamino)(4-(pyridine-4-yl)phenyl)
methyl phosphonate(4v)
White solid, mp 153155 C. IR (KBr): m 3340 (-NH), 1237
(-P = O) cm1; 1H NMR (400 MHz, TMS, CDCl3): d 8.65
(d, 2H, J = 5.7 Hz, Ar-H), 7.98 (d, 2H, J = 6.4 Hz, Ar-H),

Please cite this article in press as: Kumar, K.S. et al., Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an
ecient catalyst. Arabian Journal of Chemistry (2012), http://dx.doi.org/10.1016/j.arabjc.2012.09.009

K.S. Kumar et al.

Yield (%)

100

98.0

Yield
90

97.5
97.0

Yield (%)

Yield (%)

80
70
60

96.5

50

96.0

40

95.5

30

95.0
20
0.00

0.02

0.04

0.06

0.08

0.10

Run

Amount of the catalyst (gm)

Figure 2
Figure 1

Optimization plot of Cellulose-SO3H.

7.727.69 (m, 2H, Ar-H), 7.50 (d, 2H, J = 5.9 Hz, Ar-H),
7.227.13 (m, 2H, Ar-H), 6.44 (d, 2H, J = 6.5 Hz, Ar-H),
4.85 (brs, 1H, NH), 4.70 (d, 1H, J = 21.8, CHP), 4.184.03
(m, 2H, OCH2CH3), 4.003.86 (m, 1H, OCH2CH3), 3.74
3.60 (m, 1H, OCH2CH3), 1.31 (t, 3H, J = 7.0 Hz, OCH2CH3),
1.14 (t, 3H, J = 7.0 Hz, OCH2CH3); 13C NMR (100.57 MHz,
TMS, CDCl3): d 149.6 (C-6 & C-7), 147.6 (C-30 ), 147.5 (C-10 ),
147.2 (C-8a), 136.8 (C-4a), 136.2 (C-4), 131.8 (C-50 ), 128.2 (C-3
& C-10), 127.2 (C-4 & C-9), 122.2 (C-5 & C-8), 120.5 (C-60 ),
115.5 (C-40 ), 112.9 (C-20 ), 63.4 (d, J = 6.3 Hz, OCH2CH3),
56.9 (d, J = 151.5 Hz, P-CH), 16.3 (d, J = 6.9 Hz, OCH2
CH3); 31P NMR (161.9 MHz, H3PO4, DMSO-d6): d 24.20; Elemental analysis Calcd for C22H24N3O5P: C: 59.86%, H:

Table 3
a

Reusability of the Cellulose-SO3H.

5.48%; found C: 59.66%, H: 5.23%; LC-MS: m/z = 442

(M++1).
2.5.23. Diethyl(3-bromophenylamino)(4-(pyridine-4yl)phenyl) methylphosphonate (4w)
Light yellow solid, mp 163165 C. IR (KBr): m 3202 (-NH),
1247 (-P = O) cm1; 1H NMR (400 MHz, TMS, CDCl3): d
8.66 (d, 2H, J = 8.1 Hz, Ar-H), 7.647.50 (m, 6H, Ar-H),
6.94 (d, 1H, J = 8.0 Hz, Ar-H), 6.82 (d, 1H, J = 7.9 Hz, ArH), 6.786.49 (m, 2H, Ar-H), 5.02 (t, 1H, J = 8.2 Hz, NH),
4.79 (dd, 1H, J = 24.5, 9.1 Hz, CHP), 4.14 (m, 2H,
OCH2CH3), 3.99 (m, 1H, OCH2CH3), 3.76 (m, 1H,
OCH2CH3), 1.32 (t, 3H, J = 7.05 Hz, OCH2CH3), 1.16 (t,

Synthesis of 4aw with Cellulose-SO3H.

Entry

R1

R2

Time (min)

Yield (%)b

4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
4q
4r
4s
4t
4u
4v
4w

Ph
Ph
Ph
Ph
Ph
Ph
4(Cl)C6H4
4(Cl)C6H4
3(Cl)C6H4
4(NO2)C6H4
4(CH3)C6H4
4(CH3)C6H4
4(CH3)C6H4
4(OMe)C6H4
4(OMe)C6H4
4(OMe)C6H4
4(OMe)C6H4
4(OMe)C6H4
3,4,5(OMe)3C6H2
3,4,5(OMe)3C6H2
Furfuryl
4-(4-Pyridyl)C6H4
4-(4-Pyridyl)C6H4

Ph
4(Cl)C6H4
2(Cl)C6H4
4(OMe)C6H4
4(F)C6H4
C6H5-CH2
Ph
4(OMe)C6H4
Ph
Ph
Ph
4(OMe)C6H4
C6H5-CH2
Ph
4(NO2)C6H4
3(NO2)C6H4
4(F)C6H4
4(OMe)C6H4
4(NO2)C6H4
C6H5
C6H5
3(NO2)C6H4
3(Br)C6H4

15
20
25
20
20
15
20
25
20
30
20
25
25
25
30
30
25
25
25
30
30
30
30

98
95
94
94
93
96
92
93
92
89
94
92
94
93
94
89
90
91
88
89
86
83
84

a
b

(Wu et al., 2006)

(Vahdat et al., 2008)
(Xia and Lu, 2007)
(Wu et al., 2006)
(Wu et al., 2006)
(Wu et al., 2006)
(Wu et al., 2006)
(Wu et al., 2006)
(Bhattacharya and Rana, 2008)
(Bhattacharya and Rana, 2008)
(Wu et al., 2006)
(Wu et al., 2006)
(Wu et al., 2006)
Bhattacharya and Rana, 2008
(Bhattacharya and Rana, 2008)
(Tillu et al., 2011)
(Bhattacharya and Rana, 2008)
(Rezaei et al., 2011)
(Rezaei et al., 2011)
(Rezaei et al., 2011)
(Vahdat et al., 2008)

Characterized by their NMR.

Isolated yield calculated after purication.

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ecient catalyst. Arabian Journal of Chemistry (2012), http://dx.doi.org/10.1016/j.arabjc.2012.09.009

Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an efcient catalyst

O
P

H
H

R1

O
O

+H 2 N

R2

-H 2O
+H2O

O
O

R2
H

OEt
OEt
P

OH
+

CH

O + N

OEt
OEt
R1

NH R2

R1

O
Cellulose
l l s

Cellulose
l l s

Cellulose
l l s

Figure 3

Mechanistic pathway for the synthesis of a-aminophosphonates.

3H, J = 7.1 Hz, OCH2CH3); 13C NMR (100 MHz, TMS,

CDCl3): d 149.9 (C-6 & C-7), 147.7 (C-30 ), 147.4 (C-10 ),
147.3 (C-8a), 137.6 (C-4a), 136.6 (C-4), 130.4 (C-50 ), 128.4
(C-3 & C-10), 127.2 (C-4 & C-9), 123.0 (C-5 & C-8), 121.3
(C-60 ), 116.5 (C-40 ), 112.2 (C-20 ), 63.3 (d, J = 6.1 Hz, OCH2
CH3), 56.2 (d, J = 150.5 Hz, P-CH), 16.2 (d, J = 5.9 Hz,
OCH2CH3); 31P NMR (161.9 MHz, H3PO4, DMSO-d6): d
29.56; Elemental analysis Calcd for C22H24BrN2O3P: C:
55.59%, H: 5.09%; found C: 55.37%, H: 4.96%; HRMS: m/
z = 477.0782 (M++1).
3. Results and discussion
In continuation of our ongoing program in developing methods for the synthesis of a-aminophosphonates and identifying
new catalysts (Reddy et al., 2007), we had performed the optimization of the efciency of various catalysts on the synthesis
of a-aminophosphonates at different concentrations to the select the best catalyst (Table 1) and nally we found CelluloseSO3H as an efcient catalyst for the present reaction.
Initially, the three component reaction involving benzaldehyde, aniline and diethylphosphite by using various solvents
was performed for a period of 120 min at room temperature.
The desired a-aminophosphonates (4a) were not obtained
(Table 2, entries 14). The same reaction when run under the
solvent-free condition the expected product 4a (Table 2, entry
5) was not formed even after stirring the reaction mixture for
60 min. When Cellulose-SO3H catalyzed preparation of 4a
was performed in various solvents on the same substrates for
60 min, the product formation (Table 2, entries 69) was observed in low yields (6675%). Then nally in an effort to improve the yield further, the reaction was conducted without
solvent in the presence of Cellulose-SO3H as a catalyst. Surprisingly formation of the target product 4a was formed with
98% yield within 15 min (Table 2, entry 10).
The optimization studies of the catalyst required for the
reaction of an aldehyde, aniline with phosphate in the presence
of various amounts of catalyst ranging from 0.010.10 g
showed that the best results in terms of yields and reaction
time would be obtained with 0.04 g (Fig. 1).
When extended to variety of other substrates under the Cellulose-SO3H catalyzed solvent-free conditions, the reaction
proceeded smoothly at room temperature affording high yields
(Table 3) of the desired products (4aw) within 1530 min
without formation of any undesired by products (Scheme 1).
Also analyzed the yield of the product 4a at different runs with
the reused catalyst is represented in Fig. 2.
The scope of reactivity in view of substrates has been found
that this method is equally effective for both electron-rich as
well as electron-decient aldehydes and aniline. The reactivities

of aromatic amines with heterocyclic aldehydes such as furfuraldehyde and 4-(4-pyridyl)benzaldehyde produced corresponding products (Table 3, entry 4u, 4v and 4w) in excellent yields.
Even in the case of sterically hindered substrate trimethoxybenzaldehyde, the reaction resulted in good yields (Table 3,
entry 4s and 4t).
Here the role of Cellulose-SO3H in this method appears to
be to take away the water formed during the formation of the
imine intermediate in the rst step of the reaction by itself converting into iminium salt of cellulose sulfate. Thus the main
difculty of the reversibility in the rst step of KabachnikFields reaction, where the backward reaction occurs to form
the substrates is prevented. Subsequently, the cellulose sulfate
abstracts a proton from the H-phosphonate and renders its
phosphorus atom more nucleophilic and further catalyzes its
nucleophilic addition at the electrophilic imine carbon atom.
Thus the Cellulose-SO3H catalyzes the total reaction in both
the steps, rst by removal of water and preventing reversibility
in the rst stage and rendering phosphorus more nucleophilic
by abstraction of proton from H-phosphonate in the second
step. During this reaction Cellulose-SO3H catalyzes the reaction only by proton transfer and chemically remains as it is
for recycling (Fig. 3). Thus the simplicity and efciency of this
reaction with applicability to a wide range of different substrates, this procedure becomes the choice for the commercial
large scale industrial manufacture of a-aminophosphonates.
4. Conclusion
The present communication reports an efcient green synthesis
of a-aminophosphonates in high yield with short reaction
times at room temperature using Cellulose-SO3H as catalyst.
This method is an elegant technique for CP bond formation
by nucleophilic addition of dialkylphosphites to in situ generated imines.

Acknowledgments
The authors express their grateful thanks to Dr. S. Chandrasekhar, Scientist G, Organic Chemistry Division I, IICT,
Hyderabad, India for his helpful discussions and Council of Scientic and Industrial Research Project (01/2347/09/EMR-II)
CSIR, New Delhi, India for providing nancial support.
References
Allen, M.C., Fuhrer, W., Tuck, B., Wade, R., Wood, J.M., 1989.
Renin inhibitors. Synthesis of transition-state analog inhibitors

Please cite this article in press as: Kumar, K.S. et al., Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an
ecient catalyst. Arabian Journal of Chemistry (2012), http://dx.doi.org/10.1016/j.arabjc.2012.09.009

8
containing phosphorus acid derivatives at the scissile bond. J. Med.
Chem. 32, 16521661.
Armarego, W.L.F., Perrin, D.D., 1997. In Purication of Laboratory
Chemicals, fourth ed. Butterworth- Heinemann, Oxford.
Atherton, F.R., Hassal, C.H., Lambert, R.W., 1986. Synthesis and
structureactivity relationships of antibacterial phosphonopeptides
incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid. J. Med. Chem. 29, 2940.
Bhagat, S., Chakraborti, A.K., 2007. An extremely efcient threecomponent reaction of aldehydes/ketones, amines, and phosphites
for the synthesis of a-aminophosphonates catalyzed by magnesium
perchlorate. J. Org. Chem. 72, 12631270.
Bhattacharya, A.K., Kaur, T., 2007. An efcient one-pot synthesis of
a-amino phosphonates catalyzed by bismuth nitrate pentahydrate.
Synlett 2007, 745748.
Bhattacharya, A.K., Rana, K.C., 2008. Amberlite-IR 120 catalyzed
three-component synthesis of a-amino phosphonates in one-pot.
Tetrahedron Lett. 49, 25982601.
Chandrasekhar, S., Prakash, S.J., Jagadeshwar, V., Narsihmula, Ch.,
2001. Three component coupling catalyzed by TaCl5SiO2: synthesis of a-amino phosphonates. Tetrahedron Lett. 42, 55615563.
Cherkasov, R.A., Galkin, V.I., 1998. The Kabachnik-Fields reaction:
synthetic potential and the problem of the mechanism. Russ. Chem.
Rev. 67, 857882.
Dalko, P.I., Moisan, L., 2001. Enantioselective organocatalysis.
Angew. Chem., Int. Ed. 40, 37263748.
De Noronha, R.G., Romao, C.C., Fernandes, A.C., 2011. MoO2Cl2 as
a novel catalyst for the synthesis of a-aminophosphonates. Catal.
Commun. 12, 337340.
Emsley, J., Hall, D., 1976. The Chemistry of Phosphorous. Harper and
Row, London.
Heydari, A., Are, A., 2007. One-pot three-component synthesis of aamino phosphonate derivatives. Catal. Commun. 8, 10231026.
Heydari, A., Zarei, M., Alijanianzadeh, R., Tavakol, H., 2001. Onepot synthesis of N-trimethylsilyloxy-a-amino phosphonates from
aldehydes using lithium perchlorate/diethyl ether as a catalyst.
Tetrahedron Lett. 42, 32613629.
Heydari, A., Hamadi, H., Pourayoubi, M., 2007. A new one-pot
synthesis of a-amino phosphonates catalyzed by H3PW12O40.
Catal. Commun. 8, 12241226.
Kudrimoti, S., Bommena, V.R., 2005. (Bromodimethyl)sulfonium
bromide: an inexpensive reagent for the solvent-free, one-pot
synthesis of a-aminophosphonates. Tetrahedron Lett. 46, 1209
1210.
Kumar, A., Srivastava, S., Gupta, G., 2010. Supramolecular carbohydrate scaffold-catalyzed synthesis of tetrahydroquinolines. Tetrahedron Lett. 51, 517520.
Laschat, S., Kunz, H., 1992. Carbohydrates as chiral templates:
stereoselective synthesis of (R)- and (S)-a-aminophosphonic acid
derivatives. Synthesis 1992, 9094.
Lee, S., Park, J.H., Kang, J., Lee, J.K., 2001. Lanthanide triatecatalyzed three component synthesis of a-amino phosphonates in
ionic liquids. A catalyst reactivity and reusability study. Chem.
Commun. 17, 16981699.
Maier, L., Spoerri, H., 1991. Organic phosphorus compounds.
Resolution of 1-amino-2-(4-uorophenyl)ethylphosphonic acid as
well as some di- and tripeptides. Phosphorus, Sulfur Silicon Relat.
Elem. 61, 6975.
Manabe, K., Kobayashi, S., 2000. Facile synthesis of a-amino
phosphonates in water using a Lewis acidsurfactant-combined
catalyst. Chem. Commun. 8, 669670.
Meyer, J.H., Barlett, P.A., 1998. Design, synthesis, and evaluation of
an inhibitor bridged between P1 and P3. J. Am. Chem. Soc. 120,
46004609.
Miller, D.J., Hammond, S.M., Anderluzzi, D., Bugg, T.D.H., 1998.
Aminoalkylphosphinate inhibitors of D-ala-D-ala adding enzyme. J.
Chem. Soc., Perkin Trans. 1, 131142, Perkin Trans. 1. 1.

K.S. Kumar et al.

Mitragotri, S.D., Pore, D.M., Desai, U.V., Wadgaonkar, P.P., 2008.
Sulfamic acid: an efcient and cost-effective solid acid catalyst for
the synthesis of a-aminophosphonates at ambient temperature.
Catal. Commun. 9, 18221826.
Ordonez, M., Cabrera, H.R., Cativiela, C., 2009. An overview of
stereoselective synthesis of a-aminophosphonic acids and derivatives. Tetrahedron 65, 1749.
Pettersen, D., Marcolini, M., Bernardi, L., Fini, F., Herrera, R.P.,
Sgarzani, V., Ricci, A., 2006. Direct access to enantiomerically
enriched a-amino phosphonic acid derivatives by organocatalytic
asymmetric hydrophosphonylation of imines. J. Org. Chem. 71,
62696272.
Peyman, A., Stahl, W., Wagner, K., Ruppert, D., Budt, K.H., 1994.
Non-peptide-based inhibitors of human immunodeciency virus-1
protease. Bioorg. Med. Chem. Lett. 4, 26012604.
Prasad, G.S., Krishna, J.R., Manjunath, M., Reddy, O.V.S., Krishnaiah, M., Reddy, C.S., Puranik, V.G., 2007. Synthesis, NMR, Xray crystallography and bioactivity of some a-aminophosphonates.
ARKIVOC xiii, 133141.
Reddy, M.V.N., Kumar, B.S., Krishna, A.B., Reddy, C.S., Nayak,
S.K., Reddy, C.D., 2007. One-pot synthesis of novel a-amino
phosphonates using tetramethylguanidine as a catalyst. ARKIVOC
xv, 246254.
Reddy, M.V.N., Krishna, A.B., Reddy, C.S., 2010. Synthesis, spectral
characterization and bioassay of 3,30 -(1,4-phenylene)-bis[2-alkoxycarbonyl-alkyl)-2-thio-benzoxa-phosphinines]. Eur. J. Med. Chem.
45, 18281832.
Rezaei, Z., Khabnadideh, S., Zomorodian, K., Pakshir, K., Nadali, S.,
Mohtashami, N., Mirzaei1, E. F., 2011. Design, synthesis, and
antifungal activity of new a-aminophosphonates. Int. J. Med.
Chem., ID 678101, doi: http://dx.doi.org/10.1155/2011/678101.
Shaabani, A., Rahmati, A., Badri, Z., 2008. Sulfonated cellulose and
starch: new biodegradable and renewable solid acid catalysts for
efcient synthesis of quinolines. Catal. Commun. 2008 (9), 1316.
Sheridan, R.P., 2002. The most common chemical replacements in
drug-like compounds. J. Chem. Inf. Comput. Sci. 42, 103108.
Shinde, P.V., Kategaonkar, A.H., Shingate, B.B., Shingare, M.S.,
2011. An organocatalyzed facile and rapid access to a-hydroxy and
a-amino phosphonates under conventional/ultrasound technique.
Tetrahedron Lett. 52, 28892892.
Tillu, V.K., Dumbre, D.K., Wakharka, R.D., Choudhaty, V.R., 2011.
One-pot three-component Kabachnik-Fields synthesis of a-aminophosphonates using H-beta zeolite catalyst. Tetrahedron Lett. 52,
863866.
Vahdat, S.M., Baharfar, R., Tajbakhsh, M., Heydari, A., Baghbanian,
S.M., Khaksar, S., 2008. Organocatalytic synthesis of a-hydroxy
and a-aminophosphonates. Tetrahedron Lett. 49, 65016504.
Wu, J., Sun, W., Xia, H.G., Sun, X., 2006. A facile and highly efcient
route to a-amino phosphonates via three-component reactions
catalyzed by Mg(ClO4)2 or molecular iodine. Org. Biomol. Chem.
4, 16631666.
Xia, M., Lu, Y.D., 2007. Ultrasound-assisted one-pot approach to aamino phosphonates under solvent-free and catalyst-free conditions. Ultrasound Sonochemistry 14, 235240.
Xu, F., Luo, Y., Deng, M., Shen, Q., 2003. One-pot synthesis of aamino phosphonates using samarium diiodide as a catalyst
precursor. Eur. J. Org. Chem. 24, 47284730.
Yadav, J.S., Reddy, B.V.S., Raj, S., Reddy, K.B., Prasad, A.R., 2001.
Zr4+-catalyzed efcient synthesis of a-aminophosphonates. Synthesis, 22772280.
Zahouily, M., Elmakssoudi, A., Mezdar, A., Rayadh, A., Sebti, S.,
2007. Natural phosphate and potassium uoride doped natural
phosphate catalysed simple one-pot synthesis of a-amino phosphonates under solvent-free conditions at room temperature. Catal.
Commun. 8, 225230.

Please cite this article in press as: Kumar, K.S. et al., Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an
ecient catalyst. Arabian Journal of Chemistry (2012), http://dx.doi.org/10.1016/j.arabjc.2012.09.009