Indian Journal of Chemistry Vol. 49B, August 2010, pp. 1155-1160 Note A green approach in aqueous phase synthesis of isoxazolidine derivatives from N-phenyl- -amino nitrone and their antibacterial activities Bhaskar Chakraborty* a, Manjit Singh Chhetri a & Amalesh Samanta b a Organic Chemistry Laboratory, Sikkim Govt. College, Gangtok, Sikkim 737 102, India b Division of Microbiology, Dept. of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India E-mail: bhaskargtk@yahoo.com Received 15 April 2009; accepted (revised) 25 June 2010 1,3 Dipolar cycloaddition reaction of N-phenyl--amino nitrone with different dipolarophiles have been studied in water for the synthesis of novel isoxazolidines. Significant change in rate acceleration and high yield of these reactions are observed in water compared to organic solvents. All the synthesized compounds have been screened for their antibacterial activity and found to exihibit significant activity. Keywords: N-phenyl--amino nitrone, aqueous phase synthesis, high yield, antibacterial activity. Organic solvent free reactions have attracted considerable interest due to increasing awareness about environmental problems in chemical research and industry 1 . Water as the reaction medium is generally considered as a cheap, safe and environ- mentally benign alternative to organic solvents 2,3 . This prompted the systematic investigation into the feasibility of organic solventless reactions in aqueous media under mild conditions. 1,3 Dipolar cycloaddi- tion reaction between a nitrone and an olefinic dipolarophile is an efficient method for the synthesis of the isoxazolidine ring system 4 . Furthermore, the cycloadducts have found numerous applications in synthesis through reductive cleavage of the N-O bond to give  amino alcohols 4 while nitrones can be used as an oxidizing agent for the synthesis of aldehydes 5 . Asymmetric induction in nitrone-olefin cyclo- additions has been achieved through incorporation of chirality in both the dipole and dipolarophile 6 . Due to unstability of nitrones very few examples of the isolation or detection of the nitrones have been reported and are usually trapped in-situ by different dipolarophiles in 1,3 dipolar cycloaddition reaction to afford cycloadducts 4 . Preliminary reports about the synthesis and cycloaddition reactions of N-phenyl-- amino nitrone 1 in organic solvent has been already reported 7 . In continuation of our studies in aqueous phase isoxazolidine synthesis using -chloro nitrones 8 , the present paper reports on the synthesis and antibacterial activities of some novel isoxazolidine derivatives derived from nitrone 1 in water with high yield in a very short reaction time (Scheme I, Table I). For the present study, we have used three different maleimides, ethyl acrylate and methyl vinyl ketone (electron poor and electron rich dipolaro- philes) so as to study the nature of the cycloaddition reactions and the stereochemistry of isoxazolidine derivatives. Almost all the reactions in water are very fast (4-5 hr in case of maleimides and 5 hr for other olefins) compared to the cycloaddition reactions carried out in organic solvents (THF) which were reported to take longer periods (26-48 hr) (ref. 7). It was observed that the reactions in common organic solvents such as THF or CH 2 Cl 2 under identical reaction conditions were very slow and proceeded only partially even after 10–15 hr (ref. 7) (Table I). Hence this is a very simple and greener procedure for cycloaddition reaction in the isoxazolidine synthesis. The amount of water used in the reaction did not have any significant influence on the overall rate of the reaction and yield of the products 9 . It is possible that water promotes the reaction through hydrogen bond formation with the carbonyl oxygen atom of the , unsaturated carbonyl compounds and thereby increasing the eletrophilic character at the  carbon which is attacked by nucleophilic oxygen atom of the nitrone. Thus water activates the maleimides, ethyl acrylate, methyl vinyl ketone and thereby greatly facilitates the reaction. Results and Discussion Excellent example of introduction of chirality has been observed in nitrone additions described here. The addition of nitrone 1 to maleimides and ethyl acrylate, methyl vinyl ketone result isoxazolidine derivatives (2–6) where as many as two to three asymmetric centers are introduced in a single step. Like most of the nitrones reported from our laboratory 10-15 , nitrone 1 is also found to have