SYNTHESIS, CHARACTERIZATION OF SOME 2-AZETIDINONE DERIVATIVES FROM 4- NITRO ETHYL BENZOATE BY MICROWAVE METHOD AND EVALUATION OF THEIR ANTIMICROBIAL ACTIVITY

Received 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.

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

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

TABLE 2: SPECTRAL ANALYSIS

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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