Available online www.jocpr.com Journal of Chemical and Pharmaceutical Research, 2012, 4(2):1375-1382 Research Article ISSN : 0975-7384 CODEN(USA) : JCPRC5 1375 A facile and efficient One-pot Three Component Reaction (Kabachinik-Fields Reaction) for the Synthesis of Novel α-Aminophosphonates by 1, 4-Dimethylpiperazine as a new catalyst C. Sampath, K. Veena Vani, Y. Kotaiah, N. Hari Krishna, C. Naga Raju and C. Venkata Rao* Department of Chemistry, Sri Venkateswara University, Tirupati, India _____________________________________________________________________________________________ ABSTRACT A facile and an efficient method has been developed for the synthesis of novel α-aminophosphonates 4a-n by the one-pot three component reaction of equimolar quantities of 4-amino-N-2-thiazolyl-benzenesulfonamide (Sulfathiazole) (1), diethyl/dibutyl phosphites (2) and various aldehydes (3a-n) in dry toluene at reflux conditions via Kabachinik-Fields reaction in high yields (70-80%) in the presence of 1, 4-dimethylpiperazine as a new catalyst. Their chemical structures were established by IR, 1 H, 13 C, 31 P-NMR, mass spectral studies and elemental analyses. All the title compounds exhibited promising antibacterial, antifungal and antioxidant activities. Keywords: α-aminophosphonates, Kabachinik-Fields reaction, antibacterial activity, antifungal activity, antioxidant activity. _____________________________________________________________________________________________ INTRODUCTION The α-aminophosphonate moiety is a versatile and novel pharmacaphore due to broad spectrum of biological activity exhibited by compounds bearing this structural unit. Thus, the development of new synthetic methodologies for α-aminophosphonates has attracted the attention of medical/organic chemists. α-aminophosphonates are the important class of compounds, since they are considered to be structural analogs of the corresponding α-amino acids, as well as heterocyclic phosphonates [1] and the ω-aminophosphonates [2], with several biological activities. Their applications are significant in agriculture as plant regulators, herbicides [3], pesticides and in medicine as anti- cancer agents [4], enzyme inhibitors [5], peptide mimics [6], antibiotics and pharmacological agents [7]. A great variety of synthetic methods have been developed for the synthesis of α-aminophosphonates. Of them, Kabachinik- Fields [8] reaction is one of the most versatile pathways for the formation of carbon-phosphorus bonds. These synthetic methods are generally carried out in the presence of various bases such as potassium fluoride on alumina [9], lithium diisopropylamine (LDA) [10], 1, 8-diazabicycloundec-7-ene (DBU) [11] magnesium oxide (MgO) [12]. A few Lewis acids such as zirconium tetrachloride (ZrCl 4 ), indium trichloride (InCl 3 ), tantalum pentachloride (TaCl 5 ), ferric chloride (FeCl 3 ) and Lanthanide-triflates were also used as catalysts. In addition, antimicrobial and antioxidant activity of α-aminophosphonates have been extensively studied and well established in the literature [13- 18]. Based on the importance of α-aminophosphonates, we herein report the synthesis of novel α-aminophosphonates using 4-amino-N-2-thiazolyl-benzenesulfonamide (Sulfathiazole) 1 as an amine, diethyl/dibutyl phosphites 2, various aldehydes 3a-n and 1, 4-dimethylpiperazine as a new catalyst. EXPERIMENTAL SECTION Sigma-Aldrich, Merck and Lancaster Chemicals were used as such. Solvents used for spectroscopic and other physical studies were reagent grade and were further purified by standard procedures and techniques. The IR spectra