The convenient synthesis of a library of pyrimidineisoxazoline hybrids in 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF 6 ])-water/potassium hydroxide at ambient temperature has been accomplished. The ionic liquid [bmim] [PF 6 ], immiscible in water, can be easily recycled for reuse after separation of the products without any noticeable diminution in its activity. The protocol is rapid, the yields are good to excellent, and the method is facile.Isoxazoles and their dihydro derivatives, isoxazolines, constitute an interesting heterocyclic family with diverse and defined therapeutic significance. 1 Such compounds exhibit analgesic, antimicrobial, antifungal, and anticancer activities. They are useful intermediates for the synthesis of a variety of bioactive natural products, 2 and they have also served as lead structures for new glutamic acid ligand receptor designs, 3 such as ionotropic (iGluRs) and metabotropic Glu receptors (mGluRs).Several methods have been developed for the synthesis of isoxazolines or isoxazoles, such as the reaction of hydroxylamine with 1,3-dicarbonyl compounds, 4 a,b-unsaturated carbonyl compounds, 5 and a,b-unsaturated nitriles. 6 Previous reports reveal interesting methods for the synthesis of isoxazolines, e.g. 1,3-dipolar additions, 7 a photochemical reaction with nitrosonium tetrafluoroborate as catalyst, 8 solid-phase 1,3-dipolar cycloadditions, 9 syntheses of structurally diverse isoxazolines and isoxazoles in Magtrieve (CrO 2 ), 10 and ultrasound-promoted synthesis in water. 11 The synthesis of semisynthetic steroidal [16a,17a-d]-isoxazolines in the presence of chloramine-T in refluxing ethanol has been reported. 12 A tandem oximation-cyclization route to D 2 -isoxazolines in ethanol-sodium hydroxide 13 has also been explored.A wide variety of reagents, such as chlorine, 14 N-bromo-15 and N-chlorosuccinimide, 16 sodium hypochlorite, 17 alkyl hypochlorites, 18 chloramine-T, 19 1-chlorobenzotriazole, 20 benzyltrimethylammonium tetrachloroiodate, 21 and Ntert-butyl-N-chlorocyanamide, 22 have been used for the chloramination of aldoximes leading to isoxazoline synthesis. 1,3-Dipolar cycloadditions of nitrile oxides to various dipolarophiles 23 have been considerably accelerated in 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF 4 ]) 24 or 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF 6 ]). 25 The most convenient syntheses of isoxazolines have usually been in solvents such as dichloromethane, chloroform at 65 °C, methanolsodium hydroxide at 80 °C, toluene at 80 °C, N,N-dimethylformamide, and ethanol-sodium hydroxide. The hydrophobic ionic liquid [bmim][PF 6 ] is well known for its capability in various catalytic applications. In particular, hydrophobic media possessing hexafluorophosphate anions have a multitude of uses in different biochemical and chemical reactions. 26 We have investigated the effect of different reaction conditions involving model hydrophobic ionic liquids, such as [bmim][PF 6 ], on the formation of isoxazolines, and we illustrate...