Nano-BF3.SiO2 is an efficient, reusable and eco-friendly catalyst for various organic reactions. So, this catalyst was applied for the synthesis of biologically active phosphonates by Michaelis-Arbuzov reaction in good to excellent yields. Key advantageous of this procedure is high yielding, easy work-up procedure, short reaction time and solvent free condition. All the title compounds were characterized by spectral and elemental analysis. They were further screened for their ability towards in vitro antibacterial and antifungal activity. Majority of the title compounds showed good inhibition towards bacteria and fungi.
Keywords: Nano-BF3.SiO2, phosphonates, Michaelis-Arbuzov reaction, antibacterial and antifungal activity
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Phosphonates represent a class of stable organophosphorus compounds contain a single carbon-phosphorus (C–P) bond, are one of several pentavalent phosphorus compounds of considerable synthetic interest due to their utility as reagents in the Wadsworth-Emmons reaction1 and their applications in bioorganic chemistry.2 They are resistant to chemical and enzymatic hydrolysis, thermal decomposition 3 and photolysis.4 They are widely used as herbicides,5 pesticides,6 detergents,7 reagents for Wittig-Horner reactions,8 hybrid organic-inorganic supports and catalysts,9 antiviral agents,10 agents with antitumor activity11 or as chemical weapons of mass destruction.12 Various biomolecules which contains phosphonate motif are proved to be inhibitors of certain biosynthetic pathways. The high chemical stability of phosphonates together with their resistance to biodegradation, makes this class of compounds of particular interest for the drug design.
The Michaelis–Arbuzov rearrangement is one of the most extensively investigated reactions in organophosphorus chemistry. It is widely used in many fields of chemistry from organic synthesis to catalyst design to prepare phosphonates13 by simple SN2 reaction of nucleophilic trialkylphosphite with alkyl/aryl/arylmethyl halides to give a phosphonium intermediate which further led to phosphonate ester along with another alkyl halide. The reaction has some drawbacks such as the need for elevated temperature, removal of the trialkylphosphites used in excess, and weaker electrophiles aryl/heteroaryl halides or vinyl halides that give lower yields.
Recently, various methods were developed using different Lewis acid catalysts,14 bases such as Cs2CO3,15 and Pd-mediated cross-coupling reaction 16a-c that stimulate the M-A reaction effectively and minimize the troubles. But, they have one or more shortcomings such as long reaction time, elevated temperature, removal of the trialkylphosphites used in excess, toxic catalyst and lower yields. Recently, solid-supported heterogeneous acid catalysts are unique and have become more trendy over the past two decades. A heterogeneous catalyst, Nano BF3.SiO2 17 is a bench-top catalyst that has many advantages such as simple preparation, reusability, large surface area, strong Lewis acid character, easy handling and being environmentally benign.
On the other hand, microwave-assisted (MW-assisted) organic synthesis has been shown to provide a number of advantages over the standard heating techniques such as clean reactions, improved reaction yields and shortened reaction times, easy work-ups and/or solvent free reaction conditions.18
Keeping in mind the above points and in continuation of our research for the for the synthesis of biologically active phosphonate derivatives; we developed a new ecofriendly method by the reaction of various urea/thiourea derivatives with triethyl phosphite using 37% nano-BF3-SiO2 as ecofriendly, recyclable catalyst under microwave irradiation.
2.1. Materials and methods
The reactions were carried out in a round bottom 50 mL flask fitted with reflux condenser, a dropping funnel and in Nitrogen atmosphere. A magnetic stirrer cum hot plate was used for stirring and heating the reaction mixtures. Rota evaporator was used for removing the solvent from the reaction mixture. All the chemicals used in the present work were obtained from Sd. Fine Chem. Ltd., India; Qualigens, Mumbai and were used after purifying them by following the established procedures. All the solvents and reagents were dried and purified before use by adopting the standard procedures and techniques. Rota evaporator was used for removing the solvent from the reaction mixture. Progress of the reaction and purity of the compounds were monitored by thin layer chromatography (TLC) on aluminium sheet of silica gel 60F254, E-Merck, Germany using iodine as visualizing agent. The 1H, 13C and 31P NMR Spectra were recorded on Bruker AMX spectrometer operating at 400 MHz for 1H, 100 MHz for 13C and 161.9 MHz for 31P NMR. All compounds were dissolved in DMSO-d6 and chemical shifts were referenced to TMS (1H and 13C NMR) and 85% H3PO4 (31P NMR) and Mass spectra were recorded on API 2000 Perkin-Elmer PE-SCIEX Mass spectrometer. IR spectra were recorded on an FTIR spectrometer Bruker IFS 55 (Equinox) in KBr. Micro-analytical data were obtained from University of Hyderabad, Hyderabad, India. The 1H chemical shifts were expressed in parts per million (ppm) with reference to tetramethylsilane (TMS). The following abbreviations were used while presenting the NMR data: s = singlet, d = doublet, t = triplet, q = quartet and m = multiplet. All microwave irradiation experiments were carried out in the commercially available single-mode microwave synthesis apparatus equipped with a high sensitivity infrared sensor for temperature control and measurement.