Niobium pentoxide, a recyclable heterogeneous solid surface catalyst for the synthesis of α-amino phosphonates


Niobium pentoxide, a bifunctional solid surface catalyst, has been successfully employed to facilitate the three-component reaction between aldehydes, amines and triethyl phosphite at room temperature under solvent-free conditions to generate α-amino phosphonate in moderate to good yields. The catalyst can be recycled through simple filtration and reused to effect this transformation.

Graphic abstract

This is a preview of subscription content, access via your institution.

Figure 1
Figure 2
Figure 3


  1. 1.

    (a) Engberts J B F N, Feringn B L, Keller E and Otto S 1996 Lewis‐acid catalysis of carbon carbon bond forming reactions in water Recl. Trav. Chim. 115 457; (b) Yamamoto H Lewis Acids in Organic Synthesis Vol. 1 (Weinheim, Germany: Wiley-VCH Verlag GmbH)

  2. 2.

    (a) Hou J T, Gao J W and Zhang Z H 2011 NbCl5: an efficient catalyst for one-pot synthesis of α-aminophosphonates under solvent-free conditions Appl. Organometal. Chem. 25 47; (b) Maghsoodlou M T, Habibi-Khorassani S M, Heydari R, Hazeri N, Sajadikhah S S and Rostamizadeh M 2010 Al(H2PO4)3 as an efficient and reusable catalyst for one‐pot three‐component synthesis of α‐amino phosphonates under solvent‐free conditions Chin. J. Chem. 28 285; (c) Gallardo-Macias R and Nakayama K 2010 Tin(II) compounds as catalysts for the Kabachnik-Fields reaction under solvent-free conditions: Facile synthesis of α-aminophosphonates Synthesis 57; (d) Rezaei Z, Firouzabadi H, Iranpoor N, Ghaderi A, Jafari M R, Jafari A A and Zare H R 2009 Design and one-pot synthesis of alpha-aminophosphonates and bis(alpha-aminophosphonates) by iron(III) chloride and cytotoxic activity Eur. J. Med. Chem. 44 4266; (e) Sobhani S and Tashrifi Z 2009 Al(OTf)3 as an efficient catalyst for one-pot synthesis of primary diethyl 1-aminophosphonates under solvent-free conditions Synth. Commun. 39 120; (f) Sobhani S and Tashrifi Z 2009 One‐pot synthesis of primary 1‐aminophosphonates: Coupling reaction of carbonyl compounds, hexamethyldisilazane, and diethyl phosphite catalyzed by Al(OTf)3 Heteroat. Chem. 20 109; (g) Bhagat S and Chakraborti A K 2007 An extremely efficient three-component reaction of aldehydes/ketones, amines, and phosphites (Kabachnik−Fields reaction) for the synthesis of α-amino phosphonates catalyzed by magnesium perchlorate J. Org. Chem. 72 1263; (h) Xu F, Luo Y Q, Wu J T, Shen Q and Chen H 2006 Facile one‐pot synthesis of α‐amino phosphonates using lanthanide chloride as catalyst Heteroat. Chem. 17 389; (i) Zhan Z P and Li J P 2005 Bismuth (III) chloride–catalyzed three‐component coupling: Synthesis of α‐amino phosphonates Synth. Commun. 35 2501; (j) Ghosh R, Maiti S, Chakraborty A and Maiti D K 2004 In(OTf)3 catalysed simple one-pot synthesis of α-amino phosphonates J. Mol. Catal. A: Chem. 210 53; (k) Azizi N and Saidi M R 2003 Lithium perchlorate‐catalyzed three‐component coupling: A facile and general method for the synthesis of α‐aminophosphonates under solvent‐free conditions Eur. J. Org. Chem. 4630; (l) Ranu B C, Hajra A and Jana U 1999 General procedure for the synthesis of α-amino phosphonates from aldehydes and ketones using indium (III) chloride as a catalyst Org. Lett. 1 1141; (m) Bhagat S and Chakraborti A K 2008 Zirconium (IV) compounds as efficient catalysts for synthesis of α-aminophosphonates J. Org. Chem. 73 6029; (n) Kasthuraiah M, Kumar K A, Reddy C S and Reddy C D 2007 Syntheses, spectral property, and antimicrobial activities of 6‐α‐amino dibenzo [d,f][1,3,2]dioxaphosphepin 6‐oxides Heteroat. Chem. 18 2; (o) Xu F, Luo Y Q, Deng M Y and Shen Q 2003 One‐pot synthesis of α‐amino phosphonates using samarium diiodide as a Catalyst Precursor Eur. J. Org. Chem. 4728; (p) Chandrasekhar S, Prakash S J, Jagadeshwar V and Narsihmulu C 2001 Three component coupling catalyzed by TaCl5–SiO2: synthesis of α-amino phosphonates Tetrahedron Lett. 42 5561; (q) Ambica, Kumar S, Taneja S C, Hundal M S and Kapoor K K 2008 One-pot synthesis of α-aminophosphonates catalyzed by antimony trichloride adsorbed on alumina Tetrahedron Lett. 49 2208; (r) Cherkasov R A and Galkin V I 1998 The Kabachnik–Fields reaction: synthetic potential and the problem of the mechanism Russ. Chem. Rev. 67 857; (s) Abdel-Rahman R M, Ali T E and Abdel-Kariem S M 2016 Methods for synthesis of N-heterocyclyl/heteroaryl- α-aminophosphonates and α-(azaheterocyclyl)phosphonates Arkivoc. 183

  3. 3.

    Bekkum H V and Kouwenhoven H W 2007 Introduction to Zeolite Science and Practice Jiri Cejka, Herman van Bekkum, Avelino Corma and Ferdi Schuth (Eds.) (Amsterdam: Elsevier) Vol. 168, pp. 947–997

  4. 4.

    Gawande M B, Pandey R K and Jayaram R V 2012 Role of mixed metal oxides in catalysis science-versatile applications in organic synthesis J. Catal. Sci. Technol. 2 1113

    CAS  Article  Google Scholar 

  5. 5.

    (a) Varma R S 2002 Clay and clay-supported reagents in organic synthesis Tetrahedron 58 1235; (b) Dasgupta S and Torok B 2009 Application of clay catalysts in organic synthesis. A review Org. Prep. Proced. Int. 40 1

  6. 6.

    Kozhevnikov I V 1994 Heteropoly Acids as Catalysts for Organic Reactions Stud. Surf. Sci. Catal. 90 21

    CAS  Article  Google Scholar 

  7. 7.

    Siddiki S M A H, Rashed M N, Ali M A, Toyao T, Hirunsit P, Ehara M and Shimizu K 2019 Lewis acid catalysis of Nb2O5 for reactions of carboxylic acid derivatives in the presence of basic inhibitors ChemCatChem. 11 383

  8. 8.

    Yang S, Gao X -W, Diao C L, Song B -A, Jin L -H, Xu G -F, Zhang G -P, Wang W, Hu D -Y, Xue W, Zhou X and Lu P 2006 Synthesis and antifungal activity of novel chiral α‐aminophosphonates containing fluorine moiety Chin. J. Chem. 24 1581

    CAS  Google Scholar 

  9. 9.

    Reddy G S, Rao K U M, Sundar C S, Sudha S S, Haritha B, Swapna S and Reddy C S 2014 Neat synthesis and antioxidant activity of a-aminophosphonates Arab. J. Chem. 7 833

    Google Scholar 

  10. 10.

    Dake S A, Raut D S, Kharat K R, Mhaske R S, Deshmukh S U and Pawar R P 2011 Ionic liquid promoted synthesis, antibacterial and in vitro antiproliferative activity of novel α-aminophosphonate derivatives Bioorg. Med. Chem. Lett. 21 2527

    CAS  Article  Google Scholar 

  11. 11.

    Sivala M R, Devineni S R, Golla M, Medarametla V, Pothuru G K and Chamarthi N R 2016 A heterogeneous catalyst, SiO2-ZnBr2: An efficient neat access for α-aminophosphonates and antimicrobial activity evaluation J. Chem. Sci. 128 1303

    CAS  Article  Google Scholar 

  12. 12.

    Ramana K V, Rasheed S, Sekhar K C, Adam S and Raju C N 2012 One-pot and catalyst-free synthesis of novel α-aminophosphonates under microwave irradiation and their biological activity Der Pharmacia Lett. 4 456

    CAS  Google Scholar 

  13. 13.

    Abdou W M, Barghash R F and Bekheit M S 2011 Multicomponent reactions in a one-pot synthesis of α-aminophosphonates and α-aminophosphonic diamides with anti-inflammatory properties Monatsh Chem. 142 649

    CAS  Google Scholar 

  14. 14.

    El-Boraey H A L, El-Gokha A A A, El-Soyad I E T and Azzam M A 2015 Transition metal complexes of α-aminophosphonates Part I: synthesis, spectroscopic characterization, and in vitro anticancer activity of copper(II) complexes of α-aminophosphonates Med. Chem. Res. 24 2142

    CAS  Google Scholar 

  15. 15.

    Lejczak B, Kafarski P and Gancarz R 1988 Plant growth regulating properties of 1‐amino‐1‐methylethylphosphonic acid and its derivatives Pestic. Sci. 22 263

    CAS  Article  Google Scholar 

  16. 16.

    Bhattacharya A K, Rana K C, Pannecouque C and Clercq E D 2012 An efficient synthesis of a hydroxyethylamine (HEA) isostere and its α‐aminophosphonate and phosphoramidate derivatives as potential anti‐HIV agents ChemMedChem 7 1601

  17. 17.

    Herrera R P and Marqués-López E 2015 Multicomponent reactions: Concepts and applications for design and synthesis (New Jersey: John Wiley & Sons) Ch. 12

    Google Scholar 

  18. 18.

    (a) Mangalaraj S and amanathan C R 2012 Construction of tetrahydro-b-carboline skeletons via Brønsted acid activation of imide carbonyl group: syntheses of indole alkaloids (±)-harmicine and (±)-10-desbromoarborescidine-A RSC Adv. 2 12665; (b) Selvakumar J, Rao R S, Srinivasapriyan V, Marutheeswaran S and Ramanathan C R 2015 Synthesis of condensed tetrahydroisoquinoline class of alkaloids by employing TfOH-mediated imide carbonyl activation Eur. J. Org. Chem. 2175; (c) Harikrishnan A, Sanjeevi J and Ramanathan C R 2015 The cooperative effect of Lewis pairs in the Friedel–Crafts hydroxyalkylation reaction: a simple and effective route for the synthesis of(±)-carbinoxamine Org. Biomol. Chem. 13 3633; (d) Venkatanna K, Kumar S Y, Karthick M, Padmanaban P and Ramanathan C R 2019 A chiral bicyclic skeleton-tethered bipyridine–Zn(OTf)2 complex as a Lewis acid: enantioselective Friedel–Crafts alkylation of indoles with nitroalkenes Org. Biomol. Chem. 17 4077

  19. 19.

    (a) Harikrishnan A, Sanjeevi J and Ramanathan C R 2015 The cooperative effect of Lewis pairs in the Friedel–Crafts hydroxyalkylation reaction: a simple and effective route for the synthesis of (±)-carbinoxamine Org. Biomol. Chem. 13 3633; (b) Harikrishnan A, Selvakumar J, Gnanamani E, Bhattacharya S and Ramanathan C R 2013 Friedel–Crafts hydroxyalkylation through activation of a carbonyl group using AlBr3: an easy access to pyridyl aryl/heteroaryl carbinols New J. Chem. 37 563; (c) Gnanamani E, Someshwar N, Sanjeevi J and Ramanathan C R 2014 Conformationally rigid chiral bicyclic skeleton-tethered bipyridine N,N’-dioxide as organocatalyst: Asymmetric ring opening of meso-epoxides Adv. Synth. Catal. 356 2219

Download references


We thank the SERB, New Delhi for financial (Grant No. CRG/2019/002,960) support. AS acknowledges the UGC for the fellowship. We thank UGC-SAP, Department of Chemistry. We gratefully acknowledge the Department of Chemistry, Pondicherry University for HRMS facility (DST-FIST Sponsored); Central Instrumentation Facility, Pondicherry University for NMR and IR data.

Author information



Corresponding author

Correspondence to Chinnasamy Ramaraj Ramanathan.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 1749 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sahani, A., Rao, R.S., Vadakkayil, A. et al. Niobium pentoxide, a recyclable heterogeneous solid surface catalyst for the synthesis of α-amino phosphonates. J Chem Sci 133, 4 (2021).

Download citation


  • α-Amino phosphonates
  • Bifunctional catalyst
  • Niobium pentoxide
  • Kabachnik-fields reaction
  • Organophosphorus compounds