Synthesis of novel nitrogen containing naphtho [ 2 , 1-b ] furan derivatives and investigation of their anti microbial activities

Ethyl naphtho[2,1-b]furan-2-carboxylate has been prepared from 2-hydroxy-1naphthaldehyde 1 and ethyl chloroacetate, which on further treatment with hydrazine hydrate gave naphtha[2,1b]furan-2-carbohydrazide 3. The resulting compound 3 was treated with substituted aldehydes of 2-chloro-3-formylquinolines to give the Schiff base, which on treatment with chloro acetyl chloride gave the title compounds. The structure of the compounds has been confirmed by elemental analysis and spectral studies. The synthesized compounds were screened for their antibacterial and antifungal activities.


Results and Discussion
Ethyl naphtho[ To prepare Schiff bases 5a-l, the compound 3 was treated with various aromatic aldehydes of 2-chloro-3-formyl quinolines 4a-l in presence of catalytic amount of acetic acid in absolute ethanol.The IR spectrum of 5a exhibit absorption band at 1602 cm -1 due to -C=N and amide stretching frequency remain at 1655 cm -1 . 1 H NMR of 5a exhibits multiplets at δ 7.65-8.55ppm for 12 protons.Whereas imine protons found to resonate at δ 8.63 ppm and -NH (D 2 O exchangeable) protons appeared at δ 12.21 ppm.
Finally, to obtain the title compounds furan-2-carboxamides 6a-l, the compounds 5a-l were made to react with chloro acetyl chloride and triethylamine in dioxane.The structural analyses of the newly synthesized molecule 6a-I were confirmed by IR, 1 H NMR and mass spectral investigations.The IR spectra of the compound 6a revealed two sharp strong absorption bands at 1657 cm -1 and 1709 cm -1 for carbonyl group in azetidinone ring and amide group respectively.Further, 1 H NMR spectrum exhibited multiplets in the region at δ 7.60-8.90ppm for 12 aromatic protons.Two protons present in azetidinone ring i.e.N-CH-C and C-CH-Cl are found to resonate as doublets at δ 1.8 ppm and δ 2.5 ppm respectively.The structure was further confirmed by its Mass spectral studies.It gave molecular ion peak at m/z 476 (M + ) corresponds to molecular formula . Similarly, all these compounds were purified by column chromatography and characterized on the basis of spectral studies.The spectral details of all the synthesized compounds are given in appropriate place and are in agreement with the assigned structures.
The present protocol describes a simple and efficient method for the synthesis of azetidinones by different Schiff bases of naphtho[2,1-b]furans.It has been demonstrated that cyclocondensation of schiff bases with chloroacetyl chloride in triethyl amine revealed with fairly high yields in a relatively short reaction time and easy work-up procedures.These conditions enable this method to be good protocol for the synthesis of 2-azetidinone based heterocycles.

Experimental Section
General Procedures.All the reagents were obtained commercially and used with further purification.The melting points were determined on a Kofler hot-stage apparatus and are uncorrected; IR spectra were recorded with a FT Bruker spectrometer in KBr optics. 1 H NMR spectra were recorded on a Varian VXR-400 (400 MHz) spectrometer in DMSO-d 6 solutions.The chemical shifts were expressed in the ppm (δ scale) downfield from TMS. Microanalysis was determined on a Fisons EA 1108 instrument.Silica gel Merck (60-120 mesh) and DC-Alufolien 60 F254 were normally used for column and TLC Chromatography respectively.

Evaluation of antimicrobial activity
The in vitro antimicrobial activity was carried out against 24 hr old cultures of two bacteria and two fungi by cup-plate method. 30Compounds 6a-l (except 6b, 6d, 6f, 6g, and 6j) has been tested for their antibacterial activity against Pseudomonas aerugenosa and Staphylococcus aureus and antifungal activity against Aspergillus niger and Candida albicans.Nutrient agar and potato dextrose agars were used to culture the bacteria and fungus respectively.The compounds were tested at a concentration of 0.005 mol / ml in DMF solution.The solution of Chloramphenicol (2 mg/ ml) and Flucanazole (2 mg/ ml) were prepared in sterilized water and used as standards for comparison of antibacterial and antifungal activities respectively.The compounds were tested at varied concentration.The minimum inhibition concentration was found to be 0.001mol/ ml in DMF against all organisms.Inhibition was recorded by measuring the diameter of the inhibition zone at the end of 24 h for bacteria at 28 0 C and 48 h for fungus at 35 0 C.Each experiment was repeated thrice and the average of the three independent determinations was recorded.The protocols were summarized in (Table 1).The compounds 6c and 6e showed promising activity against P. aerugenosa and 6i, 6l and 6k against S. aureus.The compounds 6c and 6l against A. niger and 6c and 6i against C. albicans exhibited significant activity.) with hydrazine hydrate (99%), (0.50 g, 10 mmol) under acidic condition in absolute ethanol (30 ml) were refluxed for 2-3 hrs.After the completion of reaction as evidenced by TLC, the reaction mixture was poured onto crushed ice; the solid mass thus separated out was filtered, washed with water and dried to gave the desired compounds 3 in 80-85% yields.