1,3,4-oxadiazole is a five member heterocyclic ring which is a very important compound for designing potent bioactive agents. This interesting group of compound has different biological activities such as anti-inflammatory, antimicrobial, anticancer, antitubercular, anticonvulsant, anti-HIV, hypogycemic and antioxidant etc. In the present research work, we have synthesized four newly 1,3,4-oxadiazole derive atives derived from existing NSAID Ibuprofen. The purity of compounds was checked by TLC and melting point. The melting point was determined by open capillary methods and uncorrected. Structure of all four newly synthesized compounds was confirmed by spectral analysis (FTIR, and 1HNMR).
Keywords: Oxadiazole, 1, 3, 4-Oxadiazole derivatives, Heterocyclic, Ibuprofen, Cyclic compound

Gupta, M.K.

Singhai, Anuj

Journal of Drug Delivery and Therapeutics (JDDT)

Singhai et al                                                                                                               Journal of Drug Delivery & Therapeutics. 2018; 8(6-A):25-27  ISSN: 2250-1177                                                                                  [25]                                                                                 CODEN (USA): JDDTAO Available online on 10.01.2019 at http://jddtonline.info Journal of Drug Delivery and Therapeutics Open Access to Pharmaceutical and Medical Research © 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted non-commercial use, provided the original work is properly cited Open  Access                                                                                                                                                     Research Article Synthesis and Characterization of 1, 3, 4-Oxadiazole Derivatives Anuj Singhai*a, M.K. Guptab a Research Scholar, Oriental College of Pharmacy and Research, Oriental University, Indore (MP), India b Professor and Dean, Oriental College of Pharmacy and Research, Oriental University, Indore (MP), India  ABSTRACT 1,3,4-oxadiazole is a five member heterocyclic ring which is a very important compound for designing potent bioactive agents. This interesting group of compound has different biological activities such as anti-inflammatory, antimicrobial, anticancer, antitubercular, anticonvulsant, anti-HIV, hypogycemic and antioxidant etc. In the present research work, we have synthesized four newly 1,3,4-oxadiazole derive atives derived from existing NSAID Ibuprofen. The purity of compounds was checked by TLC and melting point. The melting point was determined by open capillary methods and uncorrected. Structure of all four newly synthesized compounds was confirmed by spectral analysis (FTIR, and 1HNMR). Keywords: Oxadiazole, 1, 3, 4-Oxadiazole derivatives, Heterocyclic, Ibuprofen, Cyclic compound.  Article Info: Received 25 Sep 2018;     Review Completed 28 Nov 2018;     Accepted 04 Dec 2018;     Available online 10 Jan 2019 Cite this article as:  Singhai A, Gupta MK, Synthesis and Characterization of 1, 3, 4-Oxadiazole Derivatives, Journal of Drug Delivery and Therapeutics. 2018; 8(6-A):25-27 *Address for Correspondence:  Anuj Singhai, Scholar, Oriental College of Pharmacy and Research, Oriental University, Indore (MP), India   INTRODUCTION Oxadiazole are widely used in pharmaceutical research to develop active drug substances. Among the all hetrocyclics, 1,3,4-oxadiazole is the very important class in synthetic medicinal chemistry having different biological activities  such as anti-inflammatory1, analgesic2, antimicrobial3, anti-HIV4, anticancer5, anthelmintic6, anticonvulsant7, antiviral8, hypoglycemic9, antitubercular10. Now we have synthesized some new 1,3,4-oxadiazole derivatives derived from Ibuprofen and characterized with spectral analysis.  MATERIAL AND METHODS Synthetic studies The title compounds were synthesized as given in the scheme 1. Ibuprofen was refluxed with absolute ethanol in presence of conc. Sulphuric acid to gave ester of Ibuprofen (I), this on reaction with hydrazine hydrate (99%) in absolute ethanol gave carbohydrazide of ibuprofen (II), this compound was refluxed with CS2 in ethanol in the presence of KOH gave 1,3,4 - oxadiazole attached with Ibuprofen (III). The title compounds (IVa-d) were synthesized by reaction of III with various amines in presence of formaldehyde. Spectral studies The purity of compounds was checked by TLC and melting point. The melting point was determined by open capillary methods and uncorrected. Structure of all four newly synthesized compounds was confirmed by spectral analysis (FTIR, and 1HNMR). The IR and 1H-NMR spectral data are given in the result and discussion part.  RESULT AND DISCUSSION The sequence of the reaction employed for the synthesis of title compounds is outlined in Scheme 1. The physicochemical data and spectral data of the different synthesized compounds are given in Table I and Table II. The Ibuprofen was converted to its ethyl esters (I) by esterification. The purity of the compound was confirmed by melting point, TLC and structure was confirmed by chemical test, IR and 1HNMR spectral data. IR spectra showed the characteristic peak C-H stretching at 3082 cm-1, C=O at 1730 cm-1, C-O-C at 1238 cm-1, C-Cl at 783 cm-1. This was further supported by 1H-NMR spectral data given in table II. This methyl ester was reacted with hydrazine hydrate, gave carbohydrazide (II). The purity of this compound was confirmed by melting point, TLC and structure was confirmed by IR and 1HNMR spectral data. IR spectra showed the characterstic peak C-H stretching at 3022 cm-1, C=O at 1637 cm-1, C-Cl at 770 cm-1. This was further supported by 1H-NMR spectral data with δ value given in table II. This carbohydrazide was treated with CS2/ KOH in ethanol gave 1,3,4- oxadiazole ring attached with Ibuprofen (III). The purity of the compound was confirmed by melting point, TLC Singhai et al                                                                                                               Journal of Drug Delivery & Therapeutics. 2018; 8(6-A):25-27  ISSN: 2250-1177                                                                                  [26]                                                                                 CODEN (USA): JDDTAO and structure was confirmed by IR and 1HNMR spectral data. IR spectra showed the characterstic peak of C-H stretching at 3086 cm-1, C=N at 1503 cm-1, C=S at 1162 cm-1, C-Cl at 777 cm-1. This was further supported by 1HNMR spectral data with δ value given in table II. Treatment of III with various amines in presence of formaldehyde gave the title compounds IVa-d. The purity of these compounds were assessed by melting point, TLC and Structure were confirmed by IR, and 1HNMR data. Physicochemical data and spectral data of the different synthesized title compounds (IVa-d) are given in Table I and Table II. CONCLUSION The four derivative of 1,3,4-oxadiazole were derived from Ibuprofen by different chemical reaction. All the synthesized compounds were characterized by physiochemical, chromatographically and spectral analysis. The melting point and thin-layer chromatography (TLC) were performed for check purity of the synthesized compounds. Spectral studies i.e. FTIR and 1HNMR were performed for structure confirmation. All four compounds were synthesized with good yield.  Scheme 1 Table I:  Physico-chemical data of title compounds  (IVa-d) Compound R R M.P. (°C) Yield (%) Rf * IVa  Morpholine  132-134 74.5 0.30 IVb  Diethyl amine 216-218 69.9 0.41 IVc  Piperidine  102-104 70.7 0.29 IVd  2-Methyl Piperidine 184-186 70.7 0.44  All compounds were recrystallized by methanol. Stationary phase*- silica gel G. Mobile phase- ethyl acetate: chloroform (4:1). Visualizing agent- iodine vapours.      Singhai et al                                                                                                               Journal of Drug Delivery & Therapeutics. 2018; 8(6-A):25-27  ISSN: 2250-1177                                                                                  [27]                                                                                 CODEN (USA): JDDTAO Table II: Spectral data of title compounds (IV a-d) Compound R IR spectra (KBr cm-1) 1H NMR spectra  (CDCl3,δ, ppm)   IV a  3068(C-H), 1576(C=N), 1511(C=C), 1312(C=S), 1249(C-O-C). 7.36-7.55(m, 4H, Ar-H), 3.05(s,1H, C-H), 1.93(s, 3H,CH3), 4.17(s, 2H, CH2), 2.12 (s, 2H, CH2), 1.92 (s,1H, CH), 1.12 (t, 6H, CH3, CH3 of Ibuprofen), 3.68-3.65(t, 4H,morpholine), 2.79-2.76(t, 4H, morpholine).   IV b  2967(C-H), 1575(C=N), 1501(C=C), 1322(C=S), 1276(C-O-C).  7.66-7.85(m, 4H, Ar-H), 3.15(s,1H, C-H), 1.98(s, 3H,CH3), 4.55(s, 2H, CH2), 2.22 (s, 2H, CH2), 1.97 (s,1H, CH), 1.22 (t, 6H, CH3, CH3 of Ibuprofen) , 3.02-2.60(m, 4H, CH2, CH2), 1.33-1.30(t, 6H, CH3, CH3). IV c  2926(C-H), 1575(C=N), 1505(C=C), 1352(C=S), 1245(C-O-C). 7.76-7.45(m, 4H, Ar-H), 2.95(s,1H, C-H), 1.98(s, 3H,CH3), 4.25(s, 2H, CH2), 2.22 (s, 2H, CH2), 1.96 (s,1H, CH), 1.12 (t, 6H, CH3, CH3 of Ibuprofen), 2.80-2.72(t, 4H, piperidine), 1.64(m, 2H, piperidine), 1.51-1.24(m, 4H,piperidine).   IV d  2942(C-H), 1578(C=N), 1507(C=C), 1299(C=S), 1237(C-O-C).  7.15-7.52(m, 4H, Ar-H), 3.25(s,1H, C-H), 1.96(s, 3H,CH3), 4.25(s, 2H, CH2), 2.18 (s, 2H, CH2), 1.98 (s,1H, CH), 1.17 (t, 6H, CH3, CH3 of Ibuprofen), 2.80-2.72(m, 1H, piperidine), 1.74-1.55(m, 6H, piperidine), 1.37-1.35(d, 3H, 2-methyl piperidine), 1.25(m, 2H, piperidine).  ACKNOWLEDGEMENT  The authors express their humble thanks to The Principal, College of Pharmacy and Research, Oriental University, Indore for providing necessary facilities to carry out this work.  REFERENCES [1]. Husain A, Ajmal M, Synthesis of novel 1,3,4-oxadiazole derivatives and their biological properties. Acta Pharm. 2009; 59(2):223-33. [2]. Ingale N, Maddi V, Palkar M, Ronad P, Mamledesai S, Vishwanathswamy AHM, et al. Synthesis and evaluation of anti-inflammatory and analgesic activity of 3-[(5 substituted-1,3,4-oxadiazol-2-yl-thio)acetyl]-2H-chromen-2-ones. Med Chem Res. 2012; 21:16-26. [3]. Chandrakantha B, Shetty P, Nambiyar V, Isloor N, Isloor AM, Synthesis, characterization and biological activity of some new 1,3,4-oxadiazole bearing 2-flouro-4-methoxy phenyl moiety. Eur J Med Chem. 2010; 45:1206-10. [4]. 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Synthesis and Characterization of 1, 3, 4-Oxadiazole Derivatives

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Synthesis and Characterization of 1, 3, 4-Oxadiazole Derivatives

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