VCL3 CATALYZED EFFICIENT ONE-POT SYNTHESIS OF A-AMINO PHOSPHONATES

α-Aminophosphonates are synthesized by three component condensation of aldehydes, amines and trimethylphosphite in acetonitrile by using VCI3 as catalyst. Compared to the conventional methods, this new method consistently has the advantages including excellent yields, short reaction times and mild reaction conditions. Introduction α-Aminophosphonates continue to attract increased interest as synthetic targets, because of their structural analogy to α-Aminoacids. Aminophosphates are the important class of biologically active compounds, They act as peptide mimics, enzyme inhibitors, antibiotics, crop protection agents and catalytic antibodies. As a result, a variety of synthetic approaches have been developed for the synthesis of α-Aminophosphonates. Of these methods, the nucleophilic addition of phosphates with imines, catalyzed by an acid or a base is one of the most convenient methods. It is interesting to note that the Lewis acids catalyze the reaction in much milder conditions. Among these Lewis acids such as SnCh, SnCU, BF3.0Et2, ZnC^ / MgBr2 have been used for this transformation. However, these reactions cannot be carried out in a one-pot operation starting from aldehydes. Recent reagent include ZrCU, lanthanide triflates, InCl3, LiC104-TMSCl and Montimorllonite-KSF were used for this transformation. Very recently a solvent free reaction between aldehydes, ammonium formate and dialkyl phosphite catalyzed by alumina under microwave conditions is also reported. Most of the above mentioned procedures employ dimethylphospite as the reagent, with a view to see the migration of methyl carbonium ion to that of using dimethyl (trimethyl silyl) phosphite, was the primary aim of the present investigation. The present study also aims at development of cheaper alternative reagent. Herein we report an efficient and inexpensive protocol for the synthesis of α-Aminophosphonates using catalytic amount of VCI3 under mild reaction conditions Scheme 1. * Correspondence: B. Rajitha, Department of Chemistry, National Institute of Technology, Warangal, India, Fax: 0091-9712-2459547 E-mail: ytirupatireddy@yahoo.com Vol. II. Λ'α 2, 2005 l 'C/i catalyzed efficient one-pot synthesis ofa-amino phosphonutes Ο VCI3, CH3CN R-NH X + R-NH2 + P(OCH3)3 RT Λ R Η 1 2 3 4 Scheme 1 Results and Discussion The treatment of benzaldehyde, aniline and trimethylphosphite in the presence of 10 mol percent of VCI3 in acetonitrile medium at room temperature resulted in the formation of the corresponding α-Aminophosphonates in 95% yield within 10 min. Similarly various aldehydes and amines were treated with trimethylphosphite to afford the corresponding α-Aminophosphonates at ambient temperature in high yields within 5-10 min Table-1. The reaction conditions are very mild and the α-Aminophosphonates are exclusively formed without formation of any undesired side products. The present method does not require any additives or promoters to proceed the reaction. Experimental To a stirred solution of benzaldehyde (10 mmol) and aniline (10 mmol) in acetonitrile (25 mL) was added trimethylphosphite (10 mmol) and VC13 (10 mol %). The reaction mixture was stirred at room temperature (Table 1), i. e. till the completion of the reaction as indicated by the TLC. The reaction mixture was quenched with cold water and extracted with dichloromethane (2 χ 50 mL), dried over anhydrous Na2S04 , concentrated in vacuum and purified by column chromatography (hexane: ethyl acetate, 80:20) to afford corresponding pure α-Aminophosphonates in 95% yield. In summary, we have demonstrated a novel and efficient protocol for the synthesis of aAminophosphonates using catalytic amount of VCI3. The method offers several advantages including high yields of product, very short reaction times, inexpensive catalyst, does not involve any additives to promote the reaction. Acknowledgement The authors are thankful to UGC, New Delhi for financial assistance and to the director, OCT, Hyderabad for 'H NMR and mass spectral analysis. }'. Τ. Redely el αϊ Heterocyclic Communications Table -1: VCI3 catalyzed efficient synthesis of a-Aminophosphonates Entry Aldehyde Amine Reaction Time (min) Yield (%) 4a C6H5CHO C6H5NH2 5 95 4b 2-(OH) C6H4CHO C6H5NH2 10 90 4c 4-(CH3) C6H4CHO C6H5NH2 5 94 4d 4-(OCH3) C6H5NH2 10 92 4e 2-(Cl) C6H4CHO C6H5NH2 10 90 4f 4-(CHO) C5H4N C6H5NH2 5 93 4g C6H5CHO 2-(CH3) C6H4NH2 10 94 4h C6H5CHO 4-(CH3) C6H4NH2 10 90 4i C6H5CHO 4-(Cl) C6H4NH2 10 94 4j C6H5CHO C6H5CH2NH2 10 95 4k C6H5CHO 2-(Br) C6H4NH2 15 93 41 2-(CHO) C4H3O C6H5NH2 15 94 4m 2-(CHO) C4H3O C6H5CH2NH2 15 93 All products were characterized by Η NMR, IR, and Mass spectra isolated and unoptimized yield 155 Vol. 11, No. 2, 2005 VC!3 catalyzed efficient one-pot synthesis of a-amino phosphonates References (1) a) Fileds, S. C. : Tetrahedron. 55, 1237 (1999). b) Fields, Ε. K. : J. Am. Chem. Soc. 74, 1528 (1952). c) Yuan, C., and Chen, S. : Synthesis, 1124 (1992). d) More, D. R. : J. Org. Chem. 43, 992 (1978). e) Yokomatsu, T., Yoshida, Y., Shibuya, S. : J. Org. Chem. 59, 7930 (1994). (2) Kafarski, P., Lejczak, B. : Phosphorous, Sulfur, Silicon RelatedElem. 63, 1993 (1991). (3) A) Allen, M. C., Fuhrer, W., Tuck, B., Wade, R., Wood, J. M. : J. Med. Chem. 32, 1652 (1989). b) Giannousis, P. P., Bartlet, P. A. :J. Med. Chem. 30, 1603 (1987). (4) Atherton, F. R., Hassall, C. H., Lambert, R. W.: J. Med. Chem. 29, 29 (1986). (5) a) Wieczorek, P., Lejczak, B., Kaczanowska, M., Kafarski, P. : Pestic. Sei., 30, 43 (1990). b) Nachev, I. A. : Liebigs Ann. Chem. 861 (1988). (6) Hirschmann, R., Smith III, A. B., Taylor, C. M., Benkovic, P. Α., Taylor. S. D., Yager, Κ. M., Sprengler, P. Α., Venkovic, S. J . : Science. 265, 234 (1994). (7) a) Kukhar, V. P., Solodenko, V. A. : Rus. Chem. Rev (Engl. Trans) 56, 859 (1987). b) Redmore, D.; Topics in Phosphorous Chemistry, Vol. 8; Griffith, E.J; Grayson, M.; Eds.; Wiley: New York, 515, (1976). (8) Pudovik, A. N . : Dokl. Akad. Nauk. S. R, 83, 865 (1952), Chem. Abstr. 47, 4300 (1953). (9) Baylis, Ε. K., Campbell, C. D., Dingwall, J. G.; J. Chem. Soc. Perkin. Trans. I 2845 (1984). (10) Zon, J . : Pol. J. Chem. 55, 643 (1981). Chem. Abstr. 96, 199793 (1982). (11) Yadav, J. S., Reddy, Β. V. S., Sarita, R. K., Reddy, Β. K., Prasad, A. R. : Synthesis, 2277 (2001). (12) Quian, C., Huang, T. : J. Org. Chem. 63, 4125 (1998). (13) Ranu, B. C., Hajra, Α., Jana, J . : Org. Lett. 1, 1141 (1999). (14) Sidi, M. R., Azizi, N . : Synlett., 1347 (2002). (15) Yadav, J. S., Basi, U., Subba Reddy, Madan, C. H.: Synlett. 7, 1131 (2001). (16) a) Kaboudin, B. : Chem. Lett. 880 (2001). b) Kaboudin, B., Nazari, R.: Tetrahedron Lett. 42, 8211,(2001). (17) Haydari, Α., Zarei, M., Reza, Α., Tavakol, H.: Tetrahedron Lett. 42, 3629 (2001). Received on October 26, 2004