Indian Journal of Chemistry Vol. 53B, February 2014, pp 218-226 Synthesis of some novel class of isoxazoline and isoxazolidine derivatives in ionic liquid via 1,3-dipolar cycloaddition reaction of dihydropyran derived nitrones and their antimicrobial activities Bhaskar Chakraborty* a , Amalesh Samanta b , Chiran Devi Sharma a & Nasima Khatun b a Organic Chemistry Laboratory, Sikkim Government College, Gangtok 737 102, India b Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India E-mail: bhaskargtk@yahoo.com Received 9 April 2013; accepted (revised) 13 December 2013 1,3-Dipolar cycloaddition of dihydropyran derived nitrones synthesized from 2,3 dihydro 4H-pyran and various hydroxylamines, with electron deficient alkynes are found to have significant rate acceleration and improved yields of isoxazolines in 1-Butyl-3-methylimidazolium based ionic liquids while with enals exclusively endo isoxazolidines are obtained with high selectivity. Synthetic potentiality of the novel isoxazolines and nitrones have been also tested successfully in peptide and aldehyde synthesis. All the novel isoxazoline and isoxazolidine derivatives have been screened for antimicrobial activities and found to be active. Keywords: Dihydropyran derived nitrones, cycloaddition reaction, novel isoxazolidine & isoxazolines, ionic liquid, peptides, aldehyde synthesis, antimicrobial activity Nitrones are versatile synthetic intermediates and excellent spin trapping reagents 1 . Nitrones are prepared either by condensation of aldehyde and ketones with hydroxyl amines 1 or by oxidation of the corresponding N,N–disubstituted hydroxylamines 2 . The 1,3-dipolar cycloaddition reaction between a nitrone and olefins or alkynes represents the favourite method for the construction of five-membered heterocycles commonly called isoxazolidines and isoxazolines, important frameworks of various natural products 3 . Isoxazoline and isoxazolidines posses medicinal activities such as antibacterial, anticonvulsant, antibiotic, antitubercular and antifungal activity 4,5 . Despite their potential utility, many of these procedures require high temperature and prolonged reaction times (drastic experimental conditions) and also suffer from poor regioselectivity, and lack of simplicity. In a few cases, the yields and selectivities reported are far from satisfactory due to the occurrence of several side reactions 6 . In recent times, ionic liquids have emerged as green solvents with desirable properties such as good solvating ability, wide liquidious range, tunable polarity, high thermal stability, negligible vapour pressure and ease of recyclability 7 . Therefore, classical organic reactions can be performed in these media with great advantages (yield and selectivity) as compared to conventional conditions. They are referred to as ‘designer solvents’ as their properties such as hydrophilicity, hydrophobicity, Lewis acidity, viscosity and density can be altered by the fine-tuning of parameters such as the choice of organic cation, inorganic anion and the length of alkyl chain attached to an organic cation (Figure 1). These structural variations offer flexibility to the chemist to devise the most idealized solvent, catering to the needs of any particular process. Since ionic liquids are entirely composed of non-coordinating ions, they can provide an ideal reaction medium for reactions that involve reactive ionic intermediates. Due to the stabilization of charged intermediates by ionic liquids, they can promote unprecedented selectivities and enhanced reaction rates. Consequently, ionic liquids are being used as recyclable solvents for the immobilization of transition metal based catalysts, Lewis acids and enzymes 8 . As a result of their green credentials and potential to enhance reaction rates and selectivities, ionic liquids are finding increasing applications in organic synthesis 9 with an ever-increasing quest for exploration of newer reactions in ionic liquids 10 . In continuation of the efforts to establish green methodologies in nitrone cycloaddition reactions 11-16 , herein is reported the use of ionic liquids as recyclable solvents for synthesis and 1,3-dipolar cycloaddition reaction of dihydropyran derived nitrones (having