Synthesis and Characterization of Novel Isoxazole derivatives
Lincy Joseph, Mathew George
Holy Queen College of Pharmaceutical Sciences and Research, Puthuruthy, Thrissur - 680623, Kerala.
*Corresponding Author E-mail: drlincyjoseph@gmail.com, mathewlincg@gmail.com
ABSTRACT:
1,2Isoxazoles are significant heterocycle with oxygen and nitrogen as hetero atoms belong to azole family with various therapeutic activities. Both hetero atoms oxygen and nitrogen are electronegative atoms and they are in 1,2 relationship. It’s a five membered heterocycle.3,4 Isoxazoles can be found in numerous natural products and biologically active compounds. Natural compound Ibotenic acid have isoxazole ring.5,6 Isoxazoles also form as part of many drugs, including the COX-2inhibitor valdecoxib, furoxan, is a nitric oxide donor.7 An isoxazolyl group is found in many beta-lactamase-resistant antibiotics, such as cloxacillin, dicloxacillin and flucloxacillin. The synthetic androgenic steroid danazol also has an isoxazole ring.8 A series of substituted 2-[3-(2,6-halophenyl)-5-methyl-isoxazolyl]-chromen-4-ones were synthesized by microwave irradiation method and were subjected to anti-oxidant activity. They found out presence of methyl group increased the anti-oxidant property.9 A series of isoxazoline based chalcones were prepared by the conventional Claisen-Schmidt condensation1 method under mild reaction conditions and investigated for their anti-microbial property.10
In a review paper stated Isoxazole derivatives are conferred with many biological activities such as anti-inflammatory, anticonvulsant, antibacterial, antifungal, immunoregulatory, anticancer, herbicidal, neuroleptic, antileukaemia, antidepressant activities.11 A series of compounds were prepared and assayed in a variety of biological tests for analgesic and antimicrobial activities. All the Synthesized compounds were tested for antibacterial and antifungal activity followed by cup-plate method. Among those nitro derivatives exhibited maximum anti-microbial and analgesic property.12 Some interesting benzimidazolylpyrazole derivatives were designed and synthesized. Their structures were confirmed using NMR and mass spectral analysis. The antioxidant study of the synthesized derivatives showed that among the four compounds, 5-(4-chlorophenyl)-3-(benzimidazol-2-yl)-isoxazole) showed best anti-oxidant activity.13 5-(2’-Aryl/heteroaryl chromon-6’-yl)-3-aryl/heteroaryl isoxazoles [II(a-b)] synthesized by the condensation of 1-(2’-aryl/furyl chromon-6’-yl)-3-aryl or heteroarylprop-2-en-1-ones [I(a-f)] with hydroxylamine hydrochloride. Most of the compounds have been found moderately antibacterial and anti-fungal when compared with the reference standard drugs.14 Benzofuran with fused isoxazole compounds are reported to posses, antibacterial, antifungal, anti-inflammatory and antitubercular activities.15 The benzisoxazole functional group zonisamide (1,2-benzoxazol-3-ylmethanesulfonamide) is confirmed viable drug against white spot syndrome virus.
Since Isoxazole is an important useful heterocycle, we have synthesized isoxazolines and their chemical identity characterized.
MATERIALS AND METHODS:
Synthesis:
Take 0.01mol aromatic aldehyde and 0.01mol aromatic ketone in 10ml 95% ethanol in a flask. 3.5ml 6M NaOH solution was added to the reaction mixture, stirred well for 10minutes. Cool in ice bath until crystal formation. Recrystallise from ethanol.
The formed unstable chalcones were further cyclised with 0.015mol of hydroxylamine hydrochloride and sodium acetate 0.015mol in 25ml ethanol was refluxed for 6hrs.
The mixture was concentrated and poured in to ice. The precipitate obtained was filtered washed and recrystallized from ethanol.
Reaction Scheme:
RESULTS AND DISCUSSION:
CONCLUSION:
Twenty five Isoxazole compounds have synthesized. Physico-chemical characteristics like Molecular formula, molecular weight, melting point, %yield, Rf values, Molar volume, Refractive index, surface tension, density. etc have been described appropriately. Structure of all synthesized compounds characterized spectrally. All compounds subjected for CHN analysis. There was no much variation from calculated values. Oral dosage suitability also checked. All compounds were solid in nature and gave good yield.
CONFLICT OF INTEREST:
The authors have no conflicts of interest regarding this investigation.
ACKNOWLEDGEMENT:
Authors are thankful to DST-SERB for providing fund for this research. Authors are acknowledging to STIC of Cochin University of Science and Technology for the services offered in spectral characterization of synthesized compounds.
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Received on 10.03.2023 Modified on 19.07.2023
Accepted on 17.11.2023 ©AJRC All right reserved
Asian J. Research Chem. 2023; 16(6):409-411.
DOI: 10.52711/0974-4150.2023.00066