Solvent-free synthesis of a-aminophosphonates

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

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 efficient 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; C–P bond formation; a-Aminophosphonates

Abstract a-Aminophosphonates possess a broad range of applications ranging from agrochemistry to medicine. We developed an efficient 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. ª 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 scientific research to develop many * Corresponding author. Tel.: +91 9849694958; fax: +91 877 2289555. E-mail address: [email protected] (C.S. Reddy). Peer review under responsibility of King Saud University.

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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 efficient 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 triflate, (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

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

2

K.S. Kumar et al.

Chakraborti, 2007) were identified as efficient 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 Arefi, 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 fluoride 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 trifluoride 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 difficulties 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 significant potential biological activity of a-aminophosphonates the emphasis was focused on the development of an efficient and at the same time bio-friendly sustainable synthesis for them. In this context the search for efficient 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 efficient 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 Sigma–Aldrich and Merck and used as such without further purification. All solvents used for the spectroscopic and other physical studies were reagent grade and further purified 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 (cm 1). 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 (4a–w) 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

a

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 refluxing condition.


Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an efficient 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 filtration. Dichloromethane layer was removed in a rota-evaporator. The residual product was purified 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 filtered 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 (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 &

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

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.

O O

O R1

H

+ R2

1

Scheme 1 phonates.

NH 2 + 2

H

P

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

OEt One pot, 83-98% OEt 3

R1 H

P(OE t)2 NH R 2 4a-w

Cellulose-SO3H catalyzed synthesis of a-aminophos-

3

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); 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, 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); 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, 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); 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, 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); 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, 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): d 7.42–7.26 (m, 10H, Ar-H), 4.08–4.04 (m, 2H, OCH2CH3), 3.99


4 (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); 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, 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)methyl phosphonate (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); 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, OCH2–CH3), 55.7 (Ar-OCH3), 16.4 (d, J = 5.9 Hz, O–CH2–CH3).

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, 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); 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, 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 (ArCH3), 16.3 (d, J = 6.5 Hz, O–CH2–CH3). 2.5.13. Diethyl(benzylamino)(p-tolyl)methylphosphonate (4m)

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

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): d 7.33 (d, 2H, J = 8.5 Hz, Ar-H), 7.02 (d, 2H, J = 8.5 Hz, ArH), 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 &


Solvent-free synthesis of a-aminophosphonates: Cellulose-SO3H as an efficient 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, 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)methyl phosphonate (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, ArH), 7.34–7.17 (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), 4.05–3.99 (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, 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), 4.72–4.63 (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,

5

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, 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, ArH), 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); 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, 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, ArH), 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, ArH), 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),


6

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

1

0.10

3

2

4

5

Run

Amount of the catalyst (gm)

Figure 2 Figure 1

Optimization plot of Cellulose-SO3H.

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; 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 163–165 °C. IR (KBr): m 3202 (-NH), 1247 (-P = O) cm 1; 1H NMR (400 MHz, TMS, CDCl3): d 8.66 (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, ArH), 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,

Synthesis of 4a–w 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 purification.


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

7

O P

H H

O

R1

O O

S

+H 2 N

O

R2

H

-H 2O +H2O

O O

S

R2 H

O

OEt OEt P

OH +

CH

O + N

O

O

OEt OEt

R1

NH R2

R1

O

S

O

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, 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 methods for the synthesis of a-aminophosphonates and identifying new catalysts (Reddy et al., 2007), we had performed the optimization of the efficiency of various catalysts on the synthesis of a-aminophosphonates at different concentrations to the select the best catalyst (Table 1) and finally we found CelluloseSO3H as an efficient 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 1–4). 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 6–9) was observed in low yields (66–75%). Then finally 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 0.01–0.10 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 (4a–w) within 15–30 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-deficient 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 first step of the reaction by itself converting into iminium salt of cellulose sulfate. Thus the main difficulty of the reversibility in the first 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, first by removal of water and preventing reversibility in the first 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 efficiency 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 efficient 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 C–P bond formation by nucleophilic addition of dialkylphosphites to in situ generated imines.

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