SOLID SUPPORTED MICROWAVE ASSISTED RAPID SYNTHESIS OF 1, 3, 4 OXADIAZOLESHTML Full Text
SOLID SUPPORTED MICROWAVE ASSISTED RAPID SYNTHESIS OF 1, 3, 4 OXADIAZOLES
Bhagyashri Lole, Shubhangi Waghmale and Pravina Piste *
P.G. Department of Chemistry, Yashavantrao Chavan Institute of Science Satara, (Mah.) -415001, India
ABSTRACT: We have carried out solid supported ,solvent free condition, microwave assisted rapid synthesis of 1- (2,5- substituted diphenyl)-1, 3, 4- oxadiazol -3(2H) - yl) ethanone (3a-3k) by cyclization of N'- (substituted phenyl methylidene) substituted benzohydrazide (2a-2k) in the presence of acetic anhydride and silica gel ( solid support) for 3-4 minutes by microwave irradiation giving excellent yield in short reaction time are notable advantages of this method. The structure elucidations of all the synthesized compounds have been accomplished by elemental analysis, IR, NMR and Mass spectroscopic method. The synthesized compounds (3a-3k) were screened in vitro for their antibacterial activities against S. aureus ( gram positive ) and E. coli ( gram negative ) by cup plate method . Some of the products of series were found to have quite good activities as compared to the standard drug streptomycin. The introduction of -F, -NO2, -Cl (electron withdrawing) group enhancing antibacterial activity
Microwave, Hydrazones, 1, 3, 4 oxadiazoles, antibacterial activity
INTRODUCTION: The oxadiazole and its derivatives are the important class of heterocyclic compounds and have great importance due to their applications in medicinal chemistry for the drug discovery. 1a, b The 1,3,4- oxadiazole exhibit wide range of biological activities such as antimicrobial 2, Antibacterial 3, anti-inflammatory 4, 5, anti tubercular 6, anticancer 7a, b, anthelmintic 8, antihypertensive 9. anti HIV 10, 11 and anticonvulsant12, etc. Various methods have been reported in literature for synthesis of 1, 3, 4- oxadiazoles 13, 14. The most of the methods involve cyclization of acid hydrazides by using variety of reagents such as phosphorus oxychloride, carbon disulphide, thionyl chloride, tetrahydrofuran, etc. by adopting conventional and non conventional methods.
The reactions on solid support without using solvent by microwave irradiation are recently in wide use for synthesis to create eco-friendly benign atmosphere 15. So in present work, we have developed rapid and efficient method for synthesis of 1,3,4 oxadiazoles by microwave irradiation using silica gel as solid support.
Here in, we simply report the synthesis of 1, 3, 4 oxadiazole derivatives (3a-3k) from easily available materials such as acid hydrazides and substituted aldehydes by microwave irradiation. The synthesized compounds were screened for antibacterial activity against gram positive and gram negative bacterial strain and compared it with standard drug streptomycin.
MATERIALS AND METHODS:
All the chemicals used were of synthetic grade (S. D. Fine .Chem. Ltd. Mumbai, India). The melting points of the synthesized compounds reported were uncorrected and recorded by open capillary method. The Micro-oven used for the synthesis is of Little Chef MS-192 W. The purity was checked by TLC. The progress of the reaction was monitored on percolated silica gel 60 F254 plates (Merck) using ethyl acetate: n-hexane (7:3) as an eluent and spot was detected by using iodine vapours. The structure of synthesized oxadiazole derivatives were confirmed by IR, H1NMR and Mass Spectral analysis. IR spectra were recorded on Perkin-Elmer spectrum in KBr. H1NMR spectra were recorded on 300MHz NMR spectrophotometer in CDCl3 by using tetra methyl silane as reference standard. Mass spectrum was recorded on GC-MS spectrophotometer and elemental analysis (C, H, N) was carried out on carlo - Erba elemental analyser.
Synthesis of N'-(substituted phenylmethylidene) substituted benzohydrazide (2a-2k):-
A mixture of acid hydrazide (0.01 mol) and substituted aldehyde (0.01 mol) in presence of catalytic amount of glacial acetic acid was irradiated in microwave oven for 3 min. The resulting crude product was poured on ice. The product formed was filtered, washed with water, dried and recrystalized from ethanol (Table -I).
Synthesis of 1-(2,5-substituted diphenyl)-1, 3, 4-oxadiazol-3(2H)-yl) ethanone(3a-3k):-
Silica gel (3gm) was added to the mixture of hydrazone (0.01mol) and acetic anhydride (2ml) at room temperature. The reaction mixture was thoroughly mixed; the adsorbed material was dried in air and irradiated in microwave oven (192 W) at the intervals of 30s for four min. The reaction mixture was cooled and product was extracted with methanol and poured in ice cold water gave the crude product which was filtered washed with water and recrystalized from methanol to give corresponding 1,3,4 Oxadiazoles.
TABLE 1: PHYSICAL AND ELEMENTAL ANALYSIS OF SYNTHESIZED COMPOUNDS (2a-3k):
|2c||2,4 di Cl||p-ClC6H5||81||198||51.37||2.75||8.56|
|2k||-3,5 (NO2)2||p-OCH3 C6H5||72||232||52.32||3.48||16.27|
|3k||-3,5 (NO2)2||p-OCH3 C6H5||58||218||56.98||3.91||15.64|
TABLE 2: SPECTRAL DATA OF SYNTHESIZED COMPOUNDS (3a-3k):
|Comp.No.||IR(KBr) ,√ cm-1||H1NMR ( CDCl3 ),δ in ppm||Mass|
|3a||3082(Ar-CH), 1660 (>C=O), 1625 (>C=N, str.), 1442 (C-O-C).||7.4-8 (4H, m, Ar), 7.0-7.46 (4H, m, Ar), 8.56 (s ,1H ,-CH oxadiazole), 2.01 (s, 3H, -COCH3).||--|
|3b||3208 (-OH str), 3120 (Ar-CH), 1640 (>C=O) , 1635( >C=N- str. ), 1430 (C-O-C).||7.4-8 (3H, m Ar) 9.5(1H, s, -OH) 6.62-7.0 (4H, m Ar), 8.6 (s, 1H,-CH oxadiazole), 2.04 (s, 3H, -COCH3).||--|
|3c||3057(Ar-CH), 1657 (>C=O), 1582 (>C=N- str.), 1492 (C-O-C).||7.0-7.46 (3H, m, Ar), 7.0-7.46 (4H, m, Ar) 8.52 (s, 1H, -CH oxadiazole), 1.98 (s, 3H, -COCH3).||369|
|3d||3250 (-OH str), 3035(Ar-CH), 1627(>C=O), 1554 (>C=N- str.), 1457 (C-O-C).||6.62-7.0(4H, m, Ar), 7.08-7.4 (4H, m, Ar) 8.46 (s, 1H,- CH oxadiazole), 1.96 (s, 3H, -COCH3), 9.5(s,1H, - OH).||299|
|3e||3250 (-OH str), 3070(Ar-CH), 1660(> C=O), 1590 (>C=N- str.), 1450 (C-O-C).||6.62-7.0(4H, m, Ar), 7.0-7.46 (4H, m, Ar) 8.54 (s, 1H, -CH oxadiazole), 2.02 (s, 3H, -COCH3) 9.5(s,1H,- OH).||--|
|3f||3250 (-OH str), 3050(Ar-CH), 1630 (>C=O), 1640 (>C=N- str.), 1445 (C-O-C).||6.62-7.0(8H, m, Ar), 8.58 (s, 1H,-CH oxadiazole), 1.99 (s, 3H, -COCH3) 9.5(s, 1H, -OH).||--|
|3g||3250(-OH str), 3050(Ar-CH), 1630(>C=O), 1640(>C=N- str.), 1445( C-O-C).||7.4-8 (4H, m, Ar), 6.62-7.0(4H, m, Ar), 8.58 (s, 1H, - CH oxadiazole), 2.02 (s, 3H, -COCH3) 9.5(s, 1H,- OH).||--|
|3h||3250 (-OH str), 3120(Ar-CH), 1630(>C=O), 1580 (>C=N- str.), 1460 (C-O-C).||6.62-7.0(4H, m, Ar) 7.4-8 (4H, m, Ar), 8.62 (s, 1H -CH oxadiazole), 2.04 (s, 3H,- COCH3) 9.5(s,1H, -OH).||--|
|3i||3250 (-OH str), 3080(Ar-CH), 1650(> C=O), 1645 (>C=N- str.), 1438 (C-O-C).||6.62-7.0(4H, m, Ar), 6.72-7.1(4H, m, Ar) 8.58 (s, 1H ,-CH oxadiazole), 2.1 (s, 3H, -COCH3) 3.38 (s, 3H, -OCH3), 9.5 (s,1H ,-OH).||--|
|3j||3035(Ar-CH), 1627 (>C=O), 1554 (>C=N- str.), 1457 (C-O-C).||7.4-8 (3H, m, Ar), 7.08-7.4 (4H, m, Ar), 8.52(s, 1H,-CH oxadiazole), 1.9 (s, 3H, -COCH3).||--|
|3k||3080(Ar-CH), 1650 (>C=O), 1645( >C=N- str.) , 1438 (C-O-C ).||7.4-8 (3H, m, Ar), 6.72-7.1(4H, m, Ar), 8.62 (s, 1H,- CH oxadiazole), 2.1 (s, 3H,- COCH3), 3.38 (s, 3H,- OCH3).||--|
RESULTS AND DISCUSSION: Several methods are used for synthesis of oxadiazole derivatives but some of these methods have disadvantages such as hazardous reagent, catalyst, use of toxic chemicals, longer reaction time, lower yield etc. In the present work, we have developed the solvent free condition, microwave assisted methodology for synthesis of the oxadiazole derivatives emphasing greener approach. We have synthesized series of hydrazones and cyclization with acetic anhydride and silica gel as a solid support under microwave irradiation for 3-4 mins. targeted 1,3,4 oxadiazole derivatives (3a-3k).
The reaction was completed efficiently within few minutes and product obtained was in high yield with purity. The spectral data for synthesized compounds is shown in Table 2. The structures of the synthesized compounds were confirmed by IR, H1NMR, Mass spectra. In H1 NMR spectra of compounds (3a-3k) showing singlet at 2.0 ppm due to –COCH3 and singlet at 8.5 ppm due to –CH of oxadiazole which is absent in compounds 2a-2k. IR spectra also supports above facts. It shows presence of absorption band at 1457 cm-1 indicates formation of oxadiazole ring in compounds (3a-3k) due to C-O-C which is absent in compounds 2a-2k. The compounds 3a, 3c and 3e shows M+ and M+2 peaks in 1:3 ratio in mass spectra which exhibiting presence of halogen i.e. chlorine.
All synthesized 1, 3,4 oxadiazole derivatives were screened for antibacterial activity. They are tested by using bacterial strains as Staphylococcus aureus (gram positive) and Escherichia coli (gram negative) .Streptomycin was used as standard reference. Antibacterial activity of synthesized compounds are shown in Table 2. The compounds 3b, 3c, 3j, 3k shows very good antibacterial activity as compared to standard drug streptomycin. It is observed that introduction of -F, -NO2, -Cl (electron withdrawing) group enhancing antibacterial activity. The remaining compounds show moderate antibacterial activity.
Antibacterial activities of synthesized 1, 3, 4 oxadiazole derivatives were investigated by cup plate method. The oxadiazole samples were tested in vitro against two bacterial strains - Escherichia coli (gram negative) and Staphylococcus aureus (gram positive) by measuring zone of inhibition at concentration of 10 mg/ml. The commercially available streptomycin was used as standard reference.
TABLE 3: ANTIBACTERIAL ACTIVITIES OF SYNTHESIZED OXADIAZOLE DERIVATIVES (3A-3K)
|Compound||E. Coli (in mm)||S.aureus(in mm)|
The compounds 3c and 3k shows good activity against E.coli while 3d, 3i, 3j and 3k compounds shows good activity against S.aureus and rest of them are showing moderate activity. The compounds 3c, 3k, 3d, 3i and 3j shows very good antibacterial activity as compared to standard drug streptomycin. It is observed that introduction of F, NO2, Cl ( electron withdrawing) group at meta and Para position in phenyl ring of oxadiazole moiety enhances the property.
FIG.1: ANTIBACTERIAL ACTIVITY OF SYNTHESIZED COMPOUNDS (3a-3k)
CONCLUSION: We have developed the ecofriendly microwave assisted synthetic method for synthesis of 1, 3, 4 oxadiazole derivatives.
The merits of the protocol as:
- No need of solvent
- Short reaction time
- Solid supported catalyst
- Atom economy
- Recovery of catalyst
- Exhibiting good antibacterial activity
ACKNOWLEDGEMENT: Author thanks to Department of chemistry, Y.C. Institute of Science satara for providing research facility and Shivaji University, Kolhapur for providing spectral analysis.
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How to cite this article:
Lole B, Waghmale S and Piste P: Solid Supported microwave assisted rapid Synthesis of 1, 3, 4 Oxadiazoles. Int J Pharm Sci Res 2016; 7(5): 2231-35.doi: 10.13040/IJPSR.0975-8232.7(5).2231-35.
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Bhagyashri Lole, Shubhangi Waghmale and Pravina Piste *
P.G. Department of Chemistry, Yashavantrao Chavan Institute of Science Satara, (Mah.), India
21 December, 2015
27 January, 2016
13 February, 2016
01 May 2016