Synthesis of Symmetrical and Asymmetrical Azines Encompassing Naphtho[2,1-b]furan by a Novel Approach

http://www.e-journals.net ISSN: 0973-4945; CODEN ECJHAO E-Journal of Chemistry 2011, 8(1), 354-360 Synthesis of Symmetrical and Asymmetrical Azines Encompassing Naphtho[2,1-b]furan by a Novel Approach K. VEENA, M. RAMAIAH§, G.K. VANITA, T.S.AVINASH¶ and V. P. VAIDYA* Department of Chemistry Maharani’s Science College for Women, Bangalore- 560 001, India § Department of Chemistry NMKRV College for Women, Bangalore- 560011, India ¶ Department of Studies in Microbiology Mysore University, Mysore-570006, India * Department of Chemistry Kuvempu University, Shankaraghatta- 5777411, India Received 1 June 2010; Accepted 1 August 2010 Abstract: The starting material 3-nitro-2-acetylnaphtho[2,1-b]furan (2) was obtained by nitration of 2-acetylnaphtho[2,1-b] furan (1), under mild condition. The compound 1 was synthesized by the reaction of 2-hydroxy-1-naphthaldehyde with chloroacetone, where in both condensation and cyclization took place in single step. The reaction of 3-nitro-2-acetylnaphtho[2,1-b]furan (2) with hydrazine hydrate produced corresponding hydrazone (3) in excellent yield, which on treatment with various aromatic aldehydes under different reaction conditions resulted in the formation of symmetrical azines (4a-e) and unsymmetrical azines (5a-e). All the newly synthesized compounds have been characterized by analytical and spectral studies and were screened for antibacterial antibacterial activity against Bacillus subtilus and Alcaligenes fecalies and antifungal activity against Aspergillus nidulans, Aspergillus parasiticus and Aspergillus terrus. The Second Harmonic Generation (SHG) efficiency of some of the synthesized compounds was measured by powder technique using Nd:YAG laser. Keywords: Naphthofurans, Azines, Antibacterial activity, Antifugal activity, NLO Introduction Naphtho[2,1-b]furans are associated with wide spectrum of pharmacological and biological activities. Encouraged by these findings, synthesis of various derivatives of naphtho[2,1-b] furan Synthesis of Symmetrical and Asymmetrical Azines 355 was taken up as a major research project in our laboratory1-4. Azines are organic compounds derived from condensation of an aldehyde or a ketone with hydrazine. They can be considered as 2,3-diaza analogues of butadiene. Enormous research work has been carried out on different kinds of azines, both symmetrical and asymmetrical, concerning their application in diverse fields. Azines undergo various types of cyclo addition reactions5,6. Azines, both symmetrical and asymmetrical, which are difficult to synthesize, are known to exhibit various activities and find application as Non Linear Optical (NLO) materials. Polyazines are significantly used as non-linear optical (NLO) materials because of their optical transparency7. These non-linear optical materials are of particular importance in the development of light based technology for communication and computing8. Introduction of nitro group in organic molecules, some times, enhances the activity of the compounds many folds. The fact that naphtho[2,1-b]furans are associated with wide spectrum of biological and pharmacological activities9-12 and importance of azines stimulated our interest to synthesize symmetrical and asymmical azines involving naphtha [2,1-b] furan, especially with nitro substituent on furan ring of naphthofuran moiety. Experimental Melting points were recorded in open capillaries and are uncorrected. The IR spectra were recorded on a FT-IR Research Spectrophotometer Schimadzu 8201 PC (4000-400 cm-1) and NMR on Bruker DRX-300 (300MHz-FT-NMR with low and high temperature facility -900 to +800). Standard chemical shifts are given in δ ppm values. All the reactions were monitored by thin layer chromatographic method. TLC was run on silica gel using ethyl acetate and petroleum ether (10:90) as eluent. The newly synthesized compounds were separated and purified by column chromatography using silica gel (60-120 mesh). Synthesis of 2-acetylnaphtho[2,1-b] furan (1) 2-Hydroxy-1-naphthaldehyde(5.16 g, 0.03 mol), chloroacetone(4.11 mL, 0.03 mol) and anhydrous potassium carbonate (41.5 g, 0.03 mol) were heated under reflux temperature for 24 h in dry acetone (50 mL). The reaction mixture was filtered and potassium carbonate was washed with acetone. Evaporation of the solvent from the filtrate yielded the product, 2acetylnaphtho[2,1-b] furan 1 which was recrystallised from ethanol. Mixed melting point with authentic sample did not show any depression. The IR and 1H NMR spectra of this compound superimposed with known sample. Synthesis of 3-nitro-2-acetylnaphtho[2,1-b] furan (2) A cooled nitrating mixture of concentrated nitric acid and concentrated sulphuric acid in the ratio 1:2 (13 mL : 26 mL) was added very slowly to a cooled solution of 2-acetylnaphtho [2,1-b]furan (2.24 g, 0.01 mol) in glacial acetic acid (4 mL) and the mixture was stirred for about 30 min at 5-15 0C. The stirring was continued for 3 h at the same temperature and the reaction mixture was poured on to crushed ice. The product which was separated as solid was collected, dried recrystallised from aqueous ethanol. Synthesis of 3-nitro-2-acetylnaphtho[2,1-b]furanhydrazone (3) A mixture of 3-nitro-2-acetylnaphtho[2,1-b]furan (2.5 g, 0.01 mol), hydrazine hydrate (1 mL, 0.01 mol), concentrated hydrochloric acid (3-4drops) in ethanol (30 mL) was heated on a water bath for 6 h. The reaction mixture was poured in to ice water and neutralized with aqueous sodium hydroxide (5%) The product that separated as solid was collected by filtration, dried and recrystallised from ethanol. 356 V. P. VAIDYA et al. Synthesis of Symmetrical azines (4a-e) Method A A mixture of 3-nitro-2-acetylnaphtho[2,1-b]furanhydrazone (1.39 g, 0.005 mol), benzaldehyde (0.6 mL, 0.005 mol) in ethanol (60 mL) and concentrated hydrochloric acid (3-4 drops) was refluxed on a water bath for 8 h. The reaction mixture was poured in to ice water and neutralized with aqueous sodium hydroxide (5%), solid thus separated was collected by filtration and dried. The crude product was a mixture of two compounds, as observed by TLC, having Rf values 0.85 and 0.2. These compounds were separated by column chromatography using silica gel 60-120 mesh size. One product was identified as condensed symmetrical azine (4a) and another as the regenerated 3-nitro-2-acetylnaphthofuran which was eluted using ethyl acetate. Similar procedure was adopted to obtain the compounds 4b-e from 3 using substituted benzaldehydes. Method B To a solution of 3-nitro-2-acetylnaphtho[2,1-b]furanhydrazone (1.39 g, 0.005 mol) and benzaldehyde (1.0.mL, 0.01 mol) in ethanol (60 mL) and concentrated hydrochloric acid (3-4 drops) were added and refluxed on a water bath for 8 h. The reaction mixture was poured in to ice water and neutralized with aqueous sodium hydroxide (5%). Solid thus separated was collected by filtration and dried. The crude product was a mixture of two compounds, as observed by TLC, having R (...truncated)