Indian Journal of Chemistry Vol. 52B, February 2013, pp 259-265 Synthesis and antimicrobial evaluation of novel lipophilic derivatives of pyrazolylisoxazolines Shally Chadha, Rajni Khajuria, Satya Paul & Kamal K Kapoor* Department of Chemistry, University of Jammu, Jammu 180 006, India E-mail: k2kapoor@yahoo.com Received 2 May 2011; accepted (revised) 9 November 2012 A series of novel 3-(3-phenyl-3,4-dihydro-2H-pyrazol-5-yl)-2,2-dimethylspiro{bicyclo[2.2.1]heptan-3,5-isoxazoline- 2}, 3-(2,3-diphenyl-3,4-dihydropyrazol-5-yl)-2,2-dimethylspiro{bicyclo[2.2.1]heptan-3,5-isoxazoline-2} and 5-octyl-3- (3-phenyl-3,4-dihydro-2H-pyrazol-5-yl)isoxazoline-2, 5-decyl-3-(2,3-diphenyl--3,4-dihydropyrazol-5-yl)isoxazoline-2 have been prepared and screened for their antibacterial and antifungal activities. Keywords: Isoxazoline-2, lipophilic, heterocycles, pyrazolylisoxazolines Isoxazole is an important heterocyclic nucleus which has been used extensively in pharmaceutical chemistry. Isoxazoles are potent biologically active compounds possessing antifungal 1 , antiviral 2 , antibacterial 3 , anticonvulsant 4 , anti-inflammatory, anti-tumor 5 , antimicrobial 6 , analgesic 7 and immuno- suppressive activity 8 . Considerable attention has been focused on pyrazoline derivatives due to their interesting biological activities such as antifungal, antibacterial 9 , antidepressant 10 , anticonvulsant 11 , anti- inflammatory 12 , anti-tumor 13 , anti-diabetic 14 , antihypertensive 15 and analgesic properties 16 . Keeping in view the interesting biological properties associated with isoxazoles and pyrazolines, it was conceived to synthesise molecules of general structure 1, which incorporate both these moieties as part structure (Figure 1). The lipophilic portion comprising of dimethyl bicycloheptyl or long chain alkyl is expected to help in cell penetration owing to its hydrophobic interactions with the interior of the membrane 17 . Results and Discussion 3 -Aceto-3,3-dimethylspiro{bicyclo[2.2.1]heptan- 2,5 -isoxazoline-2} 2, obtained 18 from the reaction of camphene and acetone, upon Claisen-Schmidt condensation 19 with benzaldehyde 3 generated 3 - cinnamoyl-3,3-dimethylspiro{bicyclo[2.2.1]heptan- 2,5 -isoxazoline-2} 4. Compound 4 on reaction with hydrazine hydrate in presence of KHSO 4 /SiO 2 20 yielded target compound 3 -(3-phenyl-3,4-dihydro-2H-pyrazol-5-yl)-2,2- dimethylspiro{bicyclo[2.2.1]heptan-3,5-isoxazoline- 2 } 5. The replacement of hydrazine hydrate with phenylhydrazine smoothly provided 3 -(2,3-diphenyl- 3,4-dihydropyrazol-5-yl)-2,2-dimethylspiro{bicycle- [2.2.1]heptan-3,5 -isoxazoline-2 } 6 (Scheme ). In an attempt to impart lipophilicity to the molecules by long alkyl chains instead of its cyclic counterpart, another set of experiments was performed by replacing camphene with decene and dodecene as depicted in (Scheme ). The formation was established by spectral means (vide Experimental Section). Following the same protocol, a range of compounds was synthesised using various aldehydes 3 (Schemes  and ). The synthesised compounds were screened 21-23 for their antibacterial (Staphylococcus aureus ATCC 29313, Methicillin resistant S. aureus, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) and antifungal (C. albicans ATCC 22019, C. albicans V-01-27853), Aspergillus fumigatus LSI-II, Aspergillus niger ATCC 16404) activities, but none was found effective upto a concentration of 150 g/mL. Experimental Section All melting points were measured in open capillaries on Perfit melting point apparatus and are uncorrected. Infrared spectra on KBr were recorded on Bruker-4800 infrared spectrometer. NMR and ESIMS spectra were recorded on Ac-200 (200 and