SYNTHESIS, CHARACTERIZATION OF SOME 2-AZETIDINONE DERIVATIVES FROM 4- NITRO ETHYL BENZOATE BY MICROWAVE METHOD AND EVALUATION OF THEIR ANTIMICROBIAL ACTIVITY
HTML Full TextReceived on 02 February, 2014; received in revised form, 21 March, 2014; accepted, 26 April, 2014; published 01 July, 2014
SYNTHESIS, CHARACTERIZATION OF SOME 2-AZETIDINONE DERIVATIVES FROM 4- NITRO ETHYL BENZOATE BY MICROWAVE METHOD AND EVALUATION OF THEIR ANTIMICROBIAL ACTIVITY
S.K. Gawande*1 and R.E. Khadsan 2
Department of Applied Science and Humanities, Mauli College of Engineering and Technology, Shegaon – 444 203 Dist – Buldana, Maharashtra, India
Shri D.M. Burungale Arts and Science college Shegaon- 444 203 Dist – Buldhana, Maharashtra, India
ABSTRACT: Non classical, High-speed, environmentally benign synthesis with microwaves has attracted researchers for organic synthesis a considerable amount of attention in recent years. An expeditious one pot microwave irradiation method for preparation of 2-azetidinones is developed. This method has been assessed as greener methodology. In our present study, series of five novel azetidinones are synthesised which involves the hydrazinolysis of 4- nitro ethyl benzoate with 99% hydrazine hydrate in ethanol in microwave oven to yield the hydrazides.Then hydrazides are condensed with different substituted aromaticaldehydes in DMSO in microwave to form respective Schiff base. Then formation of Schiff bases is followed by cyclisation with chloro acetyl chloride and triethyl amine in DMF to yield corresponding azetidinones. Structures of synthesised compounds were confirmed by 1H NMR, Mass spectral analysis. The compounds are evaluated for their antimicrobial activities. The activities are due to cyclic carbonyl group in azetidinones. Some of the compounds have shown comparable antimicrobial activities against all the microbial strains.
Keywords: |
Schiff base,Azetidinones, 4-nitro ethyl benzoate , Hydrazine hydrate, Microwave, Methodology, Antimicrobial- screening
INTRODUCTION: Azetidin-2-one, a four-membered cyclic lactam (β-lactam) skeleton has been recognized a useful building block for the synthesis of a large number of organic molecules by exploiting the strain energy associated with it.
water. The yellow precipitated was filtered off and washed thoroughly with water and crystallized from ethanol to give product as shown in Fig. 1.
FIG. 1: SYNTHESIS OF 4-NITRO BENZOHYDRAZIDE
STEP 2:
Synthesis of Schiff base: 4-nitro benzohydrazide (0.01mol) is treated with substituted aromatic aldehydes (0.01mol) in
DMSO in microwave oven for 2-3 min and then mixture is cooled and poured in ice cold water to obtain Schiff bases as shown in Fig. 2.
STEP 3:
Synthesis of 2-azetidinone derivatives: Schiff bases obtained in step 2 (0.01mol) in DMF on further treatment with base triethyl amine N(C2H5)3 (0.01mol) and acylatedwith mono-chloroacetyl chloride(0.01 mol) as cyclising agent in microwave oven for 3 – 4 mins to form 2-azetidinone as shown in Fig 3.
FIG. 2: SYNTHESIS OF SCHIFF BASE
FIG. 3: SYNTHESIS OF 2-AZETIDINONE DERIVATIVES
Where R is
Sr. No. | Compound | Structure |
1 | 3,4,5- trimethoxy benzaldehyde | |
2 | 4- hydroxy benzaldehyde | |
3 | 4- methoxy benzaldehyde | |
4 | 3-bromo benzaldehyde | |
5 | 4-chloro benzaldehyde |
Antimicrobial Activity: All the prepared compounds are screened for antimicrobial activity. From the microbial study it can be concluded that compounds bearing chloro, methoxy groups are more potent than remaining substituted compounds against Gram (+) and Gram (-) bacterias. All the synthesized compounds have structure activity relationship (SAR) because activity of compounds varies with substitution. On the basis of SAR it can be concluded that activity of compounds depends on electron withdrawing nature of substituted group. The sequence of the activity is as follow;
NO2 > Cl > Br > OH > OCH3 > H > CH3
RESULT AND DISCUSSION: A new method for the synthesis of various above azetidin-2-one derivatives using microwave irradiation offers significant improvements over existing procedures and thus helps facile entry into a synthesis of variety of azetidin-2-one derivatives. Also, this simple and reproducible technique affords various azetidin-2-one derivatives with short reaction times, excellent yields, and without formation of undesirable side products. The yields of different synthesized compounds were found to be in the range of 70-80% and the characterization was done by melting point, thin layer which confirm the completion of reaction. All the tested compounds showed good, moderate and poor biological activity.
TABLE -1: PHYSICAL DATA OF THE SYNTHESIZED AZETIDINONE COMPOUNDS
Compound | M.P | Yield | Molecular formula | Molecular weight |
SDT15 | 160 0 C | 82 % | C19H18 O7 N2Cl | 435 |
SDT16 | 210 0 C | 71 % | C17H14O5 N3Cl | 375 |
SDT17 | 190 0 C | 72 % | C16H11O4 N3Cl2 | 379 |
SDT18 | 100 0 C | 78 % | C16H11O4 N3ClBr | 423 |
SDT19 | 240 0 C | 72 % | C16H12O5N3Cl | 361 |
TABLE 2: SPECTRAL ANALYSIS
CODE | COMPOUND | 1H NMR (DMSO,δ ppm) | MASS (m/z) |
SDT15 | 3-chloro-4(3,4,5- trimethoxy phenyl)-N(4-nitro benzamido)-2azetidinone | 8.0-8.4(6 H, Ar-H),12.06(1H,CONH),3.3-3.8(9H, OCH3),6.0(1H, CH-Cl) | 435(M+),400,
354, 278 |
SDT16 | 3-chloro-4(4-methoxy phenyl)-N(4-nitrobenzamido)-2azetidinone | 8.0-8.4(8 H, Ar-H), 11.94 (1H,CONH),3.3-3.8(3H, OCH3),6.9(1H, CH-Cl) | 375(M+),344,
269, 223 |
SDT17 | 3-chloro-4(4-methyl phenyl)-N(4-nitrobenzamido)-2azetidinone | 8.0-8.4(8 H, Ar-H), 12.18 (1H,CONH),4.6(1H, CH-N),7.2(1H, CH-Cl) | 379(M+),381(M+2),
344, 309, 233 |
SDT18 | 3-chloro-4(3-bromo phenyl)-N(4-nitro benzamido)-2azetidinone | 8.0-8.4(8 H, Ar-H), 12.21 (1H,CONH),4.6(1H, CH-N),7.2(1H, CH-Cl) | 423(M+),377,
342, 263 |
SDT19 | 3-chloro-4(4-hydroxy phenyl)-N(4-nitro benzamido)-2azetidinone | 8.0-8.4(8 H, Ar-H), 12.21 (1H,CONH),4.61(1H, CH-N),6.7(1H, CH-Cl),9.7(1H,OH) | 361(M+),360(M-1),
344, 298 |
ACKNOWLEDGEMENTS: The authors are thankful to CDRI, Lucknow for analytical and spectral studies also thankful to Dr. C. M. Jadhao, Pricipal MGI- COET for providing basic facilities for research work. We are also thankful to Dr. Kedar Pande, Head ASH department.
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English
IJPSR
S.K. Gawande* and R.E. Khadsan
Department of Applied Science and Humanities, Mauli College of Engineering and Technology, Shegaon – 444 203 Dist – Buldana, Maharashtra, India
smita.tarale@gmail.com
02 February, 2014
21 March, 2014
26 April, 2014
http://dx.doi.org/10.13040/IJPSR.0975-8232.5(7).2966-71
01 July, 2014