suresh α aminophosphonates

Arabian Journal of Chemistry (2012) xxx, xxx–xxx

King Saud University

Arabian Journal of Chemistry

www.ksu.edu.sawww.sciencedirect.com

ORIGINAL ARTICLE

Solvent-free synthesis of a-aminophosphonates:

Cellulose-SO3H as an efficient catalyst

Krishnammagari Suresh Kumar a, Balam Satheesh Krishna a,

Chinnapareddy Bhupendra Reddy a, Mudumala Veera Narayana Reddy b,

Cirandur Suresh Reddy a,*

a Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, Indiab Department of Image Science and Engineering, Pukyong National University, Busan 608-737, Republic of Korea

Received 24 December 2011; accepted 15 September 2012

*

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KEYWORDS

Cellulose-SO3H;

Kabachnik-Fields reaction;

C–P bond formation;

a-Aminophosphonates

Corresponding author. Te

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-mail address: csrsvu@gmai

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Abstract a-Aminophosphonates possess a broad range of applications ranging from agrochemis-

try to medicine. We developed an efficient and eco-friendly Cellulose-SO3H catalyzed one-pot syn-

thesis 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.ª 2012 King Saud University. Production and hosting by Elsevier B.V. All rights reserved.

1. Introduction

a-Aminophosphonates are phosphorus structural analogs of a-amino acids (Sheridan, 2002). The medicinal importance andbiological effects of a-aminophosphonate derivatives as antibi-

otics (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 regu-

lators (Emsley and Hall, 1976) anti-thrombotic agents (Meyerand Barlett, 1998), peptidases and proteases (Miller et al.,1998), had stimulated scientific research to develop many

9849694958; fax: +91 877

.S. Reddy).

Saud University.

g by Elsevier

. Production and hosting by Elsev

9.009

Kumar, K.S. et al., Solvent-frof Chemistry (2012), http://dx

synthetic procedures for them. Based on this background over

the last few years we have synthesized and reported (Prasadet al., 2007; Reddy et al., 2010) some bioactive, antimicrobial,anti cancer and anti oxidant phosphonates.

Among the various synthetic protocols described for thesynthesis of a-aminophosphonates (Ordonez et al., 2009)nucleophilic addition of phosphites to imines i.e., Kabach-

nik-Fields reaction (Cherkasov and Galkin, 1998) proved tobe a convenient route. For the efficient and capitulate orientedsynthesis of a-aminophosphonates various other syntheticmethodologies have been reported by using different catalysts.

In such hierarchical reports Lewis acids such as lantanide tri-flate, (Manabe and Kobayashi, 2000) samarium diiodide,(Xu et al., 2003) indium (III) chloride, Lee et al., 2001 (bromo-

dimethyl) sulfonium bromide, (Kudrimoti and Bommena,2005) lithium perchlorate (Heydari et al., 2001), zirconiumtetrachloride (Yadav et al., 2001), tin tetrachloride (Laschat

and Kunz, 1992), bismuth nitrate pentahydrate (Bhattacharyaand Kaur, 2007) and magnesium perchlorate (Bhagat and

ier B.V. All rights reserved.

ee synthesis of a-aminophosphonates: Cellulose-SO3H as an.doi.org/10.1016/j.arabjc.2012.09.009

mailto:[email protected]

http://dx.doi.org/10.1016/j.arabjc.2012.09.009


http://www.sciencedirect.com/science/journal/18785352



2 K.S. Kumar et al.

Chakraborti, 2007) were identified as efficient catalysts. Sev-eral metal complexes have also been used as effective catalystsfor this reaction, (De Noronha et al., 2011) including ytter-

bium, boron, aluminium, zirconium and molybdenum com-plexes. As an alternative, the use of heteropoly acid (HPA)such as 12-tungstophosphoric acid as catalysts has also re-

ceived considerable attention (Heydari et al., 2007). In yet an-other attempt phenyltrimethylammonium chloride (Heydariand Arefi, 2007) was used as a catalyst for obtaining new gen-

eration of a-aminophosphonates. The same applicability is notexcluded for the natural phosphate alone or potassium fluoridedoped natural phosphate (Zahouily et al., 2007). Recently, theorganocatalysis 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 lessdemanding reaction conditions in comparison to the metal cat-

alyst. (Dalko and Moisan, 2001) In such sequence oxalic acid,(Vahdat et al., 2008) quinine, (Pettersen et al., 2006) and cam-phor sulfonic acid (Shinde et al., 2011) were used as potential

catalysts. Similarly some solid supported catalysts (Chandrase-khar et al., 2001) like silica supported tantalum pentachlorideand alumina-supported reagents were also exploited for

accomplishing the same results. Later on Lewis salt boron tri-fluoride diethyl etherate, transition metal oxide titanium diox-ide and some resins like amberlite-IR 120 and amberlyst-15were explored as catalysts in the synthesis of a-aminophospho-

nates (Bhattacharya and Rana, 2008). Recently, the solid acidcatalyst like montmorillonite KSF and sulfamic acid was em-ployed for this purpose (Mitragotri et al., 2008).

However, these catalysts have various drawbacks like theirnon availability difficulties in preparation and requirement oflong reaction times. Many of them when used with substrates

containing aliphatic amino groups, uncharacterizable by prod-ucts were formed. Due to significant potential biological activ-ity of a-aminophosphonates the emphasis was focused on the

development of an efficient and at the same time bio-friendlysustainable synthesis for them. In this context the search forefficient and green catalyst arose. Efforts in this direction ledto the discovery of Cellulose-SO3H that was already proved

as promising solid acid catalyst for the synthesis of some impor-tant class of organic compounds (Shaabani et al., 2008) likea-amino nitriles, quinolines and imidazoazines. In this connec-

tion, now we wish to report the Cellulose-SO3H as an efficientcatalyst for the synthesis of a-aminophosphonates from an

Table 1 Optimization of the synthesis of a-aminophosphonates.a

Entry Catalyst (mol%)

1 Catalyst free

2 Sulfamic acid (10)

3 Silica-sulfuric acid (10)

4 p-Toluenesulfonic acid (10)

5 Cellulose-SO3H (0.04)c

6 Camphorsulfonic acid (10)

7 Starch-SO3H (0.04)c

8 b-Cyclodextrin (10)

a Reaction condition: Benzaldehyde (1 mmol), Aniline (1 mmol) and

condition.b Isolated yield.cAmount maintain in gramsd Acetonitrile used as solvent.e Water used as solvent under refluxing condition.

Please cite this article in press as: Kumar, K.S. et al., Solvent-frefficient catalyst. Arabian Journal of Chemistry (2012), http://dx

aldehyde, an amine and dialkylphosphite in one pot solvent freethree component synthesis at room temperature.

2. Experimental

2.1. Materials

Chemicals were procured from Sigma–Aldrich and Merck andused as such without further purification. All solvents used for

the spectroscopic and other physical studies were reagent gradeand further purified by literature methods (Armarego andPerrin, 1997).

2.2. Characterization techniques

The melting points (mp) were determined in open capillary

tubes on a Mel-Temp apparatus (Tempo Instruments andEquip Pvt. Ltd., Mumbai, India), expressed in degrees centi-grade (�C) and are uncorrected. Infrared (IR) Spectra were ob-tained on a Nicolet (San Diego, CA, USA) 380 Fourier

transform infrared (FT-IR) spectrophotometer at the Environ-mental Engineering Laboratory, Sri Venkateswara University,Tirupati, India and samples were analyzed as potassium bro-

mide (KBr) disks and absorptions (mmax) were reported in wavenumbers (cm�1). All the compounds were dissolved in CDCl3for 1H, 13C and DMSO-d6 for

31P NMR spectra were recorded

on a Bruker (Ettlingen, Germany) AMX 400 MHz nuclearmagnetic resonance (NMR) spectrometer operating at400 MHz for 1H NMR, 100.57 MHz for 13C NMR, and

161.9 MHz for 31P NMR respectively. The chemical shiftswere expressed in delta (d) and were referenced to TMS in1H NMR and 13C NMR and 85% H3PO4 in

31P NMR. Massspectra were recorded on a QTof mass spectrometer (QSTAR

XL, Applied Biosystems/MDS Sciex, USA). Microanalysiswas 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(4a–w)

A mixture of an aldehyde (1 mmole), an amine (1 mmole),diethylphosphite (1 mmole) and Cellulose-SO3H (0.04 g) were

Time (min) Yieldb

10 (h) 50

40 59

5 (h) 87d

40 72

15 98

30 91

30 87

6 (h) 55e

diethylphosphite (1 mmol) at room temperature under solvent free



Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an efficient catalyst 3

stirred at room temperature for a particular period of time asgiven 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 Cel-lulose-SO3H and collected by filtration. Dichloromethanelayer was removed in a rota-evaporator. The residual product

was purified by silica gel column chromatography. Thecollected Cellulose-SO3H was reused for at least 3 to 4 runswithout 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) indichloromethane (20 mL), chlorosulfonic acid (1.00 g) wasadded drop wise during 2 h. After the addition the mixturewas stirred for another 2 h. The white solid thus separated

was filtered and washed with acetonitrile (30 mL) and driedat room temperature. The yield was 5.6 g.

2.5. Physical and spectral data of the products (4a–w)

2.5.1. Diethylphenyl(phenylamino)methylphosphonate (4a)

Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.46–7.45 (m, 2H, Ar-H), 7.31–7.29 (m, 3H, Ar-H), 7.08–7.07 (m,2H, Ar-H), 6.69–6.58 (m, 3H, Ar-H), 4.89–4.87 (m, 1H,NH), 4.80–4.72 (m, 1H, CHP), 4.12–4.10 (m, 2H, OCH2CH3),

3.92–3.90 (m, 1H, OCH2CH3), 3.67–3.66 (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 &

Cellulose-SO3HNeat ,r.t.,15-30 min

One pot, 83-98%

P(OEt)2R1

H NH

1 2 4a-w3

O

R1 H

OP

OEt

O

OEtHNH2R2+ +

R2

Scheme 1 Cellulose-SO3H catalyzed synthesis of a-aminophos-

phonates.

Table 2 Synthesis of a-aminophosphonates 4a.a

Entry Solvent Time (min) Yield (%)c

1 EtOH 120 nrd

2 CH2Cl2 120 nr

3 CH3CN 120 nr

4 Toluene 120 nr

5 Solvent-free 60 nr

6 EtOH+ Cellulose-SO3Hb 60 66

7 CH2Cl2 + Cellulose-SO3H 60 70

8 CH3CN+ Cellulose-SO3H 60 71

9 Toluene + Cellulose-SO3H 60 75

10 Solvent-free + Cellulose-SO3H 15 98

a Reaction conditions: room temperature, equimolar (1 mmol)

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


C-60), 69.6 (d, J= 151.5 Hz, P-CH), 62.3 (d, J = 6.3 Hz,OCH2–CH3), 16.3 (d, J= 6.9 Hz, O–CH2–CH3).

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), 4.85–4.82 (m, 1H, NH), 4.79–4.71 (m,

1H, CHP), 4.10–4.07 (m, 2H, OCH2CH3), 3.94–3.91 (m, 1H,OCH2CH3), 3.65–3.62 (m, 1H, OCH2CH3), 1.26 (t, 3H,J= 6.9 Hz, OCH2CH3), 1.09 (t, 3H, J = 6.9 Hz, OCH2CH3);13C 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, OCH2–CH3), 16.3(d, J = 5.9 Hz, O–CH2–CH3).

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), 4.86–4.82 (m, 1H, NH), 4.78–4.71 (m,

1H, CHP), 4.11–4.06 (m, 2H, OCH2CH3), 3.94–3.91 (m, 1H,OCH2CH3), 3.66–3.63 (m, 1H, OCH2CH3), 1.25 (t, 3H,J= 7.0 Hz, OCH2CH3), 1.08 (t, 3H, J = 7.0 Hz, OCH2CH3);13C 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 (C-20), 69.4 (d, J= 152.1 Hz, P-CH), 62.2 (d, J = 6.3 Hz,

OCH2–CH3), 16.3 (d, J= 6.2 Hz, O–CH2–CH3).

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), 7.32–7.30 (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), 4.14–4.08 (m,2H, OCH2CH3), 3.93–3.91 (m, 1H, OCH2CH3), 3.72–3.70(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);13C 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, OCH2–CH3), 55.8(Ar-OCH3), 16.2 (d, J= 6.3 Hz, O–CH2–CH3).

2.5.5. Diethyl (4-fluorophenylamino)(phenyl)methylphosphonate (4e)

Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.46–

6.52 (m, 9H, Ar-H), 4.87–4.85 (m, 1H, NH), 4.73–4.66 (m,1H, CHP), 4.14–4.10 (m, 2H, OCH2CH3), 3.93–3.91 (m, 1H,OCH2CH3), 3.68–3.66 (m, 1H, OCH2CH3), 1.28 (t, 3H,J= 7.0 Hz, OCH2CH3), 1.10 (t, 3H, J = 7.0 Hz, OCH2CH3);13C 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, OCH2–CH3), 16.3(d, J = 6.1 Hz, O–CH2–CH3).

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

viscous colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d7.42–7.26 (m, 10H, Ar-H), 4.08–4.04 (m, 2H, OCH2CH3), 3.99



4 K.S. Kumar et al.

(m, 1H, NH), 3.82–3.79 (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);13C 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, OCH2–CH3), 53.1(Ar-CH2-N), 16.3 (d, J= 5.9 Hz, O–CH2–CH3).

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), 4.17–4.09 (m, 2H, OCH2CH3), 3.84–3.77(m, 1H, OCH2CH3), 3.76–3.71 (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,OCH2–CH3), 16.8 (d, J= 6.0 Hz, O–CH2–CH3).

2.5.8. Diethyl(4-chlorophenyl)(4-methoxyphenylamino)methylphosphonate (4h)

Colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d 7.39–7.29 (m, 4H, Ar-H), 6.70–6.50 (m, 4H, Ar-H), 4.70–4.62 (m,

1H, CHP), 4.53–4.51 (m, 1H, NH), 4.14–4.09 (m, 2H,OCH2CH3), 4.03–3.94 (m, 1H, OCH2CH3), 3.81–3.80 (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);13C 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, OCH2–CH3),55.7 (Ar-OCH3), 16.4 (d, J = 5.9 Hz, O–CH2–CH3).

2.5.9. Diethyl(3-chlorophenyl)(phenylamino)methylphosphonate (4i)

White solid, mp 90–92 �C; 1H NMR (400 MHz, TMS, CDCl3):

d 7.50 (s, 1H, Ar-H), 7.39 (d, 1H, J = 7.5 Hz, Ar-H), 7.29–7.22(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), 4.18–4.11 (m, 2H,

OCH2CH3), 3.98–3.88 (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, OCH2–CH3), 16.1 (d,J= 6.2 Hz, O–CH2–CH3).

2.5.10. Diethyl(4-nitrophenyl)(phenylamino)methylphosphonate (4j)

Bright yellow solid, mp 122–124 �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), 7.06–6.55 (m, 5H, Ar-H), 5.21 (brs,1H, NH), 4.90 (d, 1H, J= 25.2 Hz, CHP), 4.17–3.86 (m,4H, OCH2CH3), 1.26 (t, 3H, J= 6.9 Hz, OCH2CH3), 1.16


(t, 3H, J = 6.9 Hz, OCH2CH3);13C NMR (100.57 MHz,

TMS, CDCl3): d 147.8 (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, OCH2–CH3), 16.8 (d, J = 6.1 Hz,O–CH2–CH3O–CH2–CH3).

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), 4.14–4.08(m, 2H, OCH2CH3), 3.95–3.92 (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);13C 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, OCH2–CH3), 21.4(Ar-CH3), 16.7 (d, J= 6.9 Hz, O–CH2–CH3).

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), 3.95–3.92 (m, 1H, OCH2CH3),

3.71–3.69 (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, OCH2–CH3), 55.9 (Ar-OCH3), 21.3 (Ar-CH3), 16.3 (d, J = 6.5 Hz, O–CH2–CH3).

2.5.13. Diethyl(benzylamino)(p-tolyl)methylphosphonate (4m)

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), 4.85–4.83 (m, 1H, NH), 4.70–4.63 (m, 1H,

CHP), 4.14–4.10 (m, 2H, OCH2CH3), 3.92–3.91 (m, 1H,OCH2CH3), 3.79–3.67 (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, OCH2–CH3), 50.1(Ar-CH2-N), 21.7 (Ar-CH3), 16.6 (d, J= 6.4 Hz, O–CH2–CH3).

2.5.14. Diethyl(4-methoxyphenyl)(phenylamino)methylphosphonate (4n)

Viscous colorless liquid; 1H NMR (400 MHz, TMS, CDCl3): d7.33 (d, 2H, J= 8.5 Hz, Ar-H), 7.02 (d, 2H, J= 8.5 Hz, Ar-H), 6.77–6.52 (m, 5H, Ar-H), 5.20 (brs, 1H, NH), 4.63 (d,1H, J = 23.7 Hz, CHP), 4.07–3.61 (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 &




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, OCH2–CH3), 55.9 (Ar-OCH3), 16.3 (d,

J = 6.9 Hz, O–CH2–CH3).

2.5.15. Diethyl(4-methoxyphenyl)(4-nitrophenylamino)methyl

phosphonate (4o)

Yellow solid, mp 112–114 �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), 3.90–3.81 (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, OCH2–CH3), 16.1 (d,J = 6.0 Hz, O–CH2–CH3).

2.5.16. Diethyl(4-methoxyphenyl)(3-nitrophenylamino)methylphosphonate (4p)

Yellow solid, mp 149–151 �C; 1H NMR (400 MHz, TMS,

CDCl3): d 7.65 (s, 1H, Ar-H), 7.45 (d, 2H, J = 8.5 Hz, Ar-H), 7.34–7.17 (m, 2H, Ar-H), 7.09 (t, 1H, J = 6.7 Hz, Ar-H), 6.87 (d, 2H, J = 8.2 Hz, Ar-H), 5.60 (brs, 1H, NH), 5.11(d, 1H, J = 23.1 Hz, CHP), 4.05–3.99 (m, 2H, OCH2CH3),

3.90–3.86 (m, 1H, OCH2CH3), 3.77–3.73 (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, O–CH2–CH3).

2.5.17. Diethyl(4-fluorophenylamino)(4-methoxyphenyl)methyl

phosphonate (4q)

White solid, mp 52–54 �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, Ar-

H), 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), 4.72–4.63 (m, 1H, CHP), 4.10–4.03 (m, 2H, OCH2CH3), 3.90–3.70 (m, 1H, OCH2CH3),3.68 (s, 3H, Ar-OCH3), 3.64–3.63 (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,OCH2–CH3), 55.9 (Ar-OCH3), 16.5 (d, J = 6.2 Hz, O–CH2–

CH3).

2.5.18. Diethyl(4-methoxyphenyl)(4-methoxyphenylamino)

methyl phosphonate (4r)

White solid, mp 118–120 �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), 4.12–4.03 (m, 2H, OCH2CH3), 3.92–3.87(m, 1H, OCH2CH3), 3.70–3.62 (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);13C 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 (C-20 & 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, OCH2–CH3), 55.6

(Ar-OCH3), 55.2 (Ar-OCH3), 16.5 (d, J = 6.9 Hz, O–CH2–CH3).

2.5.19. Diethyl (4-nitrophenylamino)(3,4,5-trimethoxyphenyl)methylphosphonate (4s)

White solid, mp 90–92 �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, Ar-

H), 6.83 (s, 2H, Ar-H), 5.42 (brs, 1H, NH), 4.63 (d, 1H,J= 24.2 Hz, CHP), 4.11–4.04 (m, 2H, OCH2CH3), 3.91–3.89(m, 1H, OCH2CH3), 3.71–3.62 (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);13C 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 (C-

20 & 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, OCH2–CH3), 56.1(Ar-OCH3), 55.8 (Ar-OCH3), 16.1 (d, J = 6.7 Hz, O–CH2–

CH3).

2.5.20. Diethyl(phenylamino)(3,4,5-trimethoxyphenyl)methyl

phosphonate (4t)

White solid, mp 109–111 �C; 1H NMR (400 MHz, TMS,CDCl3): d 7.10–7.03 (m, 3H, Ar-H), 6.81–6.75 (m, 4H, Ar-H), 5.41 (brs, 1H, NH), 4.62 (d, 1H, J= 24.2 Hz, CHP),

4.10–4.03 (m, 2H, OCH2CH3), 3.92–3.88 (m, 1H, OCH2CH3),3.72–3.63 (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, OCH2–CH3), 60.8 (Ar-OCH3), 56.1 (Ar-OCH3),16.4 (d, J = 6.3 Hz, O–CH2–CH3O–CH2–CH3).

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), 7.47–7.42 (m, 1H, Ar-H), 7.28–7.23 (m,

1H, Ar-H), 7.11–7.07 (m, 1H, Ar-H), 6.99–6.78 (m, 4H, Ar-H), 5.72 (brs, 1H, NH), 4.08–4.02 (m, 2H, OCH2CH3), 3.91–3.73 (m, 1H, OCH2CH3), 3.69 (s, 3H, Ar-OCH3), 3.65–3.61

(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, OCH2–CH3), 16.5 (d, J = 6.1 Hz,

O–CH2–CH3).

2.5.22. Diethyl(3-nitrophenylamino)(4-(pyridine-4-yl)phenyl)methyl phosphonate(4v)

White solid, mp 153–155 �C. IR (KBr): m 3340 (-NH), 1237(-P = O) cm�1; 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),



0.00 0.02 0.04 0.06 0.08 0.10

20

30

40

50

60

70

80

90

100Yi

eld

(%)

Amount of the catalyst (gm)

Yield (%)

Figure 1 Optimization plot of Cellulose-SO3H.

1 2 3 4 5

95.0

95.5

96.0

96.5

97.0

97.5

98.0

Yiel

d (%

)

Run

Yield

Figure 2 Reusability of the Cellulose-SO3H.

6 K.S. Kumar et al.

7.72–7.69 (m, 2H, Ar-H), 7.50 (d, 2H, J = 5.9 Hz, Ar-H),7.22–7.13 (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), 4.18–4.03

(m, 2H, OCH2CH3), 4.00–3.86 (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, OCH2–CH3),

56.9 (d, J = 151.5 Hz, P-CH), 16.3 (d, J= 6.9 Hz, O–CH2–CH3);

31P NMR (161.9 MHz, H3PO4, DMSO-d6): d 24.20; Ele-mental analysis Calcd for C22H24N3O5P: C: 59.86%, H:

Table 3 Synthesis of 4a–w with Cellulose-SO3H.

Entrya R1 R2

4a Ph Ph

4b Ph 4(Cl)C6H4

4c Ph 2(Cl)C6H4

4d Ph 4(OMe)C6H4

4e Ph 4(F)C6H4

4f Ph C6H5-CH2

4g 4(Cl)C6H4 Ph

4h 4(Cl)C6H4 4(OMe)C6H4

4i 3(Cl)C6H4 Ph

4j 4(NO2)C6H4 Ph

4k 4(CH3)C6H4 Ph

4l 4(CH3)C6H4 4(OMe)C6H4

4m 4(CH3)C6H4 C6H5-CH2

4n 4(OMe)C6H4 Ph

4o 4(OMe)C6H4 4(NO2)C6H4

4p 4(OMe)C6H4 3(NO2)C6H4

4q 4(OMe)C6H4 4(F)C6H4

4r 4(OMe)C6H4 4(OMe)C6H4

4s 3,4,5(OMe)3C6H2 4(NO2)C6H4

4t 3,4,5(OMe)3C6H2 C6H5

4u Furfuryl C6H5

4v 4-(4-Pyridyl)C6H4 3(NO2)C6H4

4w 4-(4-Pyridyl)C6H4 3(Br)C6H4

a Characterized by their NMR.b Isolated yield calculated after purification.


5.48%; found C: 59.66%, H: 5.23%; LC-MS: m/z = 442(M++1).

2.5.23. Diethyl(3-bromophenylamino)(4-(pyridine-4-yl)phenyl) methylphosphonate (4w)

Light yellow solid, mp 163–165 �C. IR (KBr): m 3202 (-NH),1247 (-P = O) cm�1; 1H NMR (400 MHz, TMS, CDCl3): d8.66 (d, 2H, J= 8.1 Hz, Ar-H), 7.64–7.50 (m, 6H, Ar-H),6.94 (d, 1H, J= 8.0 Hz, Ar-H), 6.82 (d, 1H, J= 7.9 Hz, Ar-H), 6.78–6.49 (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,

Time (min) Yield (%)b

15 98 (Wu et al., 2006)

20 95 (Vahdat et al., 2008)

25 94 (Xia and Lu, 2007)

20 94 (Wu et al., 2006)

20 93 (Wu et al., 2006)

15 96 (Wu et al., 2006)

20 92 (Wu et al., 2006)

25 93 (Wu et al., 2006)

20 92 (Bhattacharya and Rana, 2008)


20 94 (Wu et al., 2006)

25 92 (Wu et al., 2006)

25 94 (Wu et al., 2006)

25 93 Bhattacharya and Rana, 2008


30 89 (Tillu et al., 2011)


25 91 (Rezaei et al., 2011)

25 88 (Rezaei et al., 2011)

30 89 (Rezaei et al., 2011)

30 86 (Vahdat et al., 2008)

30 83

30 84



l l s

O

S

O

OO

H OH

R1

+H2N R2-H2O

+H2O

O

S

O

OO NR2

H R1

+

PH OEt

OEt

O

R1CH

P

NH

O OEtOEt

R2

+

O

S

OH

OO

Cellulose

l l sCellulose

l l sCellulose

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,

OCH2–CH3);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 meth-ods for the synthesis of a-aminophosphonates and identifyingnew catalysts (Reddy et al., 2007), we had performed the opti-

mization of the efficiency of various catalysts on the synthesisof a-aminophosphonates at different concentrations to the se-lect the best catalyst (Table 1) and finally we found Cellulose-SO3H as an efficient catalyst for the present reaction.

Initially, the three component reaction involving benzalde-hyde, aniline and diethylphosphite by using various solventswas performed for a period of 120 min at room temperature.

The desired a-aminophosphonates (4a) were not obtained(Table 2, entries 1–4). The same reaction when run under thesolvent-free condition the expected product 4a (Table 2, entry

5) was not formed even after stirring the reaction mixture for60 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 6–9) was ob-served in low yields (66–75%). Then finally in an effort to im-prove the yield further, the reaction was conducted withoutsolvent in the presence of Cellulose-SO3H as a catalyst. Sur-

prisingly formation of the target product 4a was formed with98% 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 presenceof various amounts of catalyst ranging from 0.01–0.10 gshowed 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 Cel-

lulose-SO3H catalyzed solvent-free conditions, the reactionproceeded smoothly at room temperature affording high yields

(Table 3) of the desired products (4a–w) within 15–30 minwithout 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-deficient aldehydes and aniline. The reactivities


of aromatic amines with heterocyclic aldehydes such as furfur-aldehyde and 4-(4-pyridyl)benzaldehyde produced correspond-ing products (Table 3, entry 4u, 4v and 4w) in excellent yields.

Even in the case of sterically hindered substrate trimethoxy-benzaldehyde, the reaction resulted in good yields (Table 3,entry 4s and 4t).

Here the role of Cellulose-SO3H in this method appears tobe to take away the water formed during the formation of theimine intermediate in the first step of the reaction by itself con-

verting into iminium salt of cellulose sulfate. Thus the maindifficulty of the reversibility in the first step of Kabachnik-Fields reaction, where the backward reaction occurs to form

the substrates is prevented. Subsequently, the cellulose sulfateabstracts a proton from the H-phosphonate and renders itsphosphorus atom more nucleophilic and further catalyzes itsnucleophilic addition at the electrophilic imine carbon atom.

Thus the Cellulose-SO3H catalyzes the total reaction in boththe steps, first by removal of water and preventing reversibilityin the first stage and rendering phosphorus more nucleophilic

by abstraction of proton from H-phosphonate in the secondstep. During this reaction Cellulose-SO3H catalyzes the reac-tion only by proton transfer and chemically remains as it is

for recycling (Fig. 3). Thus the simplicity and efficiency of thisreaction with applicability to a wide range of different sub-strates, this procedure becomes the choice for the commerciallarge scale industrial manufacture of a-aminophosphonates.

4. Conclusion

The present communication reports an efficient green synthesisof a-aminophosphonates in high yield with short reactiontimes at room temperature using Cellulose-SO3H as catalyst.This method is an elegant technique for C–P bond formation

by nucleophilic addition of dialkylphosphites to in situ gener-ated imines.

Acknowledgments

The authors express their grateful thanks to Dr. S. Chandrase-khar, Scientist – G, Organic Chemistry Division – I, IICT,Hyderabad, India for his helpful discussions and Council of Sci-entific and Industrial Research Project (01/2347/09/EMR-II)

CSIR, New Delhi, India for providing financial support.

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