2-Hydroxy-5-phenylbenzaldehyde on iodination yielded 2-Hydroxy-3-iodo-5-phenylbenzaldehyde. This aldehyde on facile condensation with substituted aromatic amines in presence of catalytic amount of acetic acid to afford new series of Schiff bases. Further these Schiff bases on cyclocondensation reaction with chloroacetyl chloride afforded a biologically active 2-azetidinones derivatives. The structure of newly synthesized compounds characterized on the basis of elemental analysis and spectral data. The compounds prepared were tested against Xanthomonas citri, Escherichia coli, Erwinia carotovora and Bacillus subtilis. Some of these compounds showed potential antibacterial activity

Junne, Subhash B

Kadam, Archana B

Shinde, Saheb L

Vibhute, Yeshwant B

Zangade, Sainath B

English

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International Multidisciplinary Research Journal 2012, 2(6):44-47 ISSN: 2231-6302 Available Online: http://irjs.info/    Synthesis and antibacterial activity of some new schiff bases and 2-Azetidinones containing iodohyydroxy biphenyl moiety  Subhash B. Junne1*, Archana B. Kadam1, Sainath B. Zangade1, Saheb L. Shinde2 and Yeshwant B. Vibhute1  1Organic Synthesis Laboratory, P. G. Department of studies in Chemistry, Yeshwant Mahavidyalaya, Nanded (MS.) India. 2Department of Botany, Yeshwant Mahavidyalaya, Nanded (MS.) India.   Abstract  2-Hydroxy-5-phenylbenzaldehyde on iodination yielded 2-Hydroxy-3-iodo-5-phenylbenzaldehyde. This aldehyde on facile condensation with substituted aromatic amines in presence of catalytic amount of acetic acid to afford new series of Schiff bases. Further these Schiff bases on cyclocondensation reaction with chloroacetyl chloride afforded a biologically active 2-azetidinones derivatives. The structure of newly synthesized compounds characterized on the basis of elemental analysis and spectral data. The compounds prepared were tested against Xanthomonas citri, Escherichia coli, Erwinia carotovora and Bacillus subtilis. Some of these compounds showed potential antibacterial activity.  Keywords: 2-Hydroxy-3-iodo-5-phenylbenzaldehyde, Schiff bases, 2-azetidinones, antibacterial activity.  INTRODUCTION       The utility of Schiff bases lay in their usefulness as synthons in the synthesis of bioactive molecules such as 4-thiazolidinines, 2-azetidinones, benzoxazines, formazans, etc. Schiff bases are known to have useful biological activity like insecticidal [1], antibacterial [2], antituberculosis [3], antimicrobial [4] and anticonvulsant [5] activities. They also serve as a back bone for the synthesis of various heterocyclic compounds. The presence of azomethine and sulfonamide functional group is responsible for antimicrobial activity, which can be altered depending upon the type of substituent present on the aromatic rings.      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. Efforts have been made in exploring such new aspects of β-lactam chemistry versatile intermediates for their synthesis of aromatic β-amino acid and their derivatives, peptides, polyamines, polyamino alcohols, amino sugars and polyamino ethers [6]. The cyclic 2-azetidinone skeleton has been extensively used as a template to build the heterocyclic structure fused to the four membered rings. The β-lactam heterocycles are still the most prescribed antibiotics used in medicine. They are considered as an important contribution of science to humanity [7]. The most widely used antibiotics such as the penicillins, cephalosporins, carumonam, thienamycine, aztreonam and the norcardicins all contain β-lactum rings [8]. The long-term use of β-lactam antibiotics exerts selective pressure on bacteria and permits the proliferation of resistant organisms [9]. Azetidinones are of great biological interest, especially as antitubercular [10], antibacterial [11 and 12], antifungal [13] and as anti-inflammatory, anticonvulsant activity [14]. As part of interest in heterocycles that have been explored for developing pharmaceutically important molecules, 4-thiazolidinones [15] and 2-azetidinones [16] have played an important role in medicinal chemistry, it was thought worthwhile to synthesize some new 2-azetidinones derivatives. All synthesized compounds were assessed for their antibacterial activity against Xanthomonas citri, Escherichia coli, Erwinia Carotovora and Bacillus subtilis using disc diffusion method [17]. Ampicillin, Stryptomycin was used as standard antibiotics for comparison. Their structures were confirmed by IR, HNMR and elemental analysis.   Scheme     Received: April 07, 2012; Revised: May 03, 2012; Accepted: June 02, 2012.  *Corresponding Author Subhash B. Junne  Organic Synthesis Laboratory, P. G. Department of studies in Chemistry, Yeshwant Mahavidyalaya, Nanded (MS.) India.  Email: sbjunne@gmail.com    International Multidisciplinary Research Journal 2012, 2(6):44-47  45R R1 R2 R3 R4 H H NO2 H I H H I H NO2 H H I H Cl H H Cl H I I H CH3 H I I H NO2 H I CH3 I H NO2 H H H COOH H I I H COOH H I I H H NO2 H H H H CI I H H I H COOH Cl H I H Cl  MATERIALS AND METHODS       All melting points were taken in open capillaries and are uncorrected. FT-IR spectra were recorded on perkin-Elmer-157 spectrophotometer instrument using KBr discs. 1HNMR were taken on a Bruker WN-400 FTMHz NMR instrument using DMSO/CdCl3 solvent and TMS as a internal standard (chemical shift in δ ppm). The purity of the compounds was monitored by thin layer chromatography.  Typical Procedure for Preparation of Schiff Bases       Equimolar  quantity of  2-hydroxy -3- iodo -5-phenyl benzaldehyde (0.01 mmol) and substituted aromatic amines(0.01mmol) in requisite  methanol (15-20 ml) containing few drops of acetic  acid was refluxed for 3 hr. The resultant solution was cooled and poured in cold water. The separated solid was filtered, recrystallized from ethyl alcohol. Physical and analytical data is given in table 1.  Spectroscopic data of selected compounds  N-(4-nitro-6-iodo phenyl)-2-iodo-4-hydroxy biphenyl,5-yl azomethine (Ia)      Yield: 80%; Melting point: 155 0C. IR (KBr, cm-1): 3015 (-OH), 1620, (C=N), 1500, 1470, 1400(C=C) 1420, 1560 (-NO2). 1H NMR (DMSO-d6): 7.10-8.0 (m, 10H, Ar-H), 8.2 (s, 1H, N=CH), 13.2 (s, 1H, Ar-OH). MS (m/z): 570(M+). Anald. Calcd. for C19H12N2O3I2: C, 40.00, H, 2.01, N, 4.91 Found  C, 40.05, H,2.18, N, 4.98.  N-(4-chloro-6-iodophenyl)-2-iodo-4-hydroxy biphenyl,5-yl Azomethine (Id) Yield: 80%; Melting point: 110 0C. IR (KBr,cm-1): 3019 (-0H), 1612 (C=N), 1466, 144, 1384, 1354 (C=C), 1H NMR (DMSO-d6): 7.23-7.90 (m, 10H, Ar-H), 8.15 (s, 1H=CH), 13.01 (s,1H.-OH), MS (m/z): 559, (M+100), 432 (50), 305 (04), 277 (03), 241 (03), 139 (07), 86 (04). Anald. Calcd. for C19H12NOClI2: C, 40.78, H, 2.14, N, 2.50 Found C, 40.70, H, 2.10, N, 2.54.  N-(2,6-di-iodo-4-methyl phenyl)-2-iodo-4-hydroxy biphenyl,5-yl azomethine (Ie)      Yield: 75%; Melting point: 120oC; IR (KBr cm-1,): 3050 (-OH), 2910 (-CH3), 1650 (C=N) 1490, 1410, 1390(C=C).1HNMR (DMSO-d6):; 2.1 (s, 3H,CH3), 6.9-8.0 (m, 9H, Ar-H), 8.1 (s, 1H, N=CH). 13.2 (s, 1H, OH). MS (m/z): 665(M+).  Anald. Calcd. for C20H14NOI3: C, 36.09, H, 2.10, N, 2.10 Found  C, 36.14, H, 2.15, N, 2.16.  N-(3-iodo-5-nitro-2-methyl phenyl)-2-iodo-4-hydroxy biphenyl, 5-yl azomethine (Ig)      Yield: 72%; Melting point: 1600C. IR(KBr,cm-1): 3019(-OH), 1610(C=N), 1462, 1440, 1390, 1390, 1365(C=C), 1HNMR (DMSO-d6): 2.5 (s, 3H, CH3),7.23-7.85 (m, 10H, Ar-H), 8.15 (s, 1H, =CH), 13.02 (s, 1H, OH), MS (m/z): 584(M+). Anald. Calcd. for C20H14N2O3I2: C, 18.39, H, 1.58,, N, 4.01 Found  C, 18.42, H, 1.49,N, 4.06.  N-(4-carboxylic-6-iodo phenyl)-2-iodo-4-hydroxy biphenyl, 5-yl azomethine (Ih)      Yield: 78%; Melting point: 130 0C. IR (KBr,cm-1): 3010-3215 (-OH), 1650 (C=N), 1740 C=O),1490, 1450, 1400, (C=C), 1H NMR(DMSO-d6): 7.0-1.1 (m, 10H, Ar-H), 8.3 (s, 1H, N=CH), 11.1 (s, 1H, OH), 13.2 (s, 1H, Ar-OH). MS (m/z): 559(M+).  Anald. Calcd. for C20H13NO3I2: C, 42.17, H, 2.28, N, 2.46  Found C, 42.22, H, 2.21, N, 2.41.  N-(2,6dichloro-4-iodo phenyl)-2-iodo-4-hydroxy biphenyl,5-yl Azomethine (Im)      Yield: 80%; Melting point: 75 0C; IR (KBr, cm-1): 3015 (-OH), 1635 (C=N), 1520, 1475, 1400. 1H NMR (DMSO-d6), 7.-8.1 (m, 9H, Ar-H), 8.3 (s, 1H, N=CH), 13.2 (s, 1H, Ar-OH). MS (m/z): 594(M+).  Anald. Calcd. for C19H11NOCl2I2: C, 33.38, H, 1.85, N, 2.35  Found  C, 38.32, H, 1.90, N, 2.41.  Typical Procedure for Preparation of 2-Azetidinones       A solution of Shciff base (0.01 mmole) in dry dioxane (50 ml) was added to a well stirred mixture of chloroacetyl chloride (0.012 mmole) and triethylamine (0.03 mmole) in dry dioxane at 00C. The reaction mixture was stirred further for 6 hr. Excess of dioxane was removed by evaporation and then residue poured into cold water. The separated solid thus obtain was filtered, washed with water and recrystallized from ethyl alcohol: 1-4 dioxane. Physical and analytical data is given in Table 1.  3-chloro-4-(4-hydroxy-5-iodobiphenyl-3-yl)-1-(2-iodo-4-nitrophenyl)azetidin-2-one (IIa):       Yield: 72%; Melting point: 2340C; IR (KBr, cm-1): 3325 (OH), 1730 (C=O), 1610, 1550, 1490 (C=C), 1510, 1370, (NO2). 1H NMR (DMSO-d6): 2.5 (s, 1H, -CH), 4.2 (s, 1H, -CHCl), 7.3-8.5 (m, 10H, Ar-H), 13.1 (s, 1H, Ar-OH). MS (m/z): 646(M+).  Anald. Calcd for C21H13N2O4ClI2: C, 39.00, H, 2.01, N, 4.33  Found  C, 39.08, H, 2.08, N, 4.36  3-chloro-4-(4-hydroxy-5-iodobiphenyl-3-yl)-1-(4-chloro-6-iodophenyl)azetidin-2-one (IId):      Yield: 68%; Melting point: 232oC. IR (KBr,cm-1): 3348 (OH), 1726 (C=O), 1600, 1579, 1577, 1490 (C=C). 1H NMR (DMSO-d6). 2.6 (s, 1H, -CH), 4.25 (s, 1H, -CHCl), 7.22-8.25 (m, 10H, Ar-H), 13.2 (s, 1H, ArH). MS (m/z): 636(M+).  Anal. Calcd for C21H13NO2Cl2I2: C,39.62; H, 2.04, N, 2.20,  Found  C, 39.68; H, 2.09; N,2.12.  3-chloro-4-(4-hydroxy-5-iodobiphenyl-3-yl)-1-(2,6-di-iodo-4-mehthylphenyl)azetidin-2-one (IIe):      Yield: 65%; Melting point: 240oC. IR (KBr, cm-1): 3350 (OH), 2920 (-CH3), 1725 (C=O), 1610, 1580, 1515(C=C). 1H NMR (DMSO-d6):  2.1 (d, 3H, CH3), 2.4 (s, 1H, CH), 4.4 (s, 1H, CH), 7.0-8.2 (m, 9H, ArH), 13.3 (s, 1H, ArOH). MS (m/z): 741(M+).  Anal. Calcd for S.B.Junne et al.,   46C22H15NO2ClI3: C, 35.62, H, 2.02, N, 1.88. Found C, 35.67, H, 2.10, N,1.93.  3-chloro-4-(4-hydroxy-5-iodobiphenyl-3-yl)-1-(3-iodo-5-nitro-2-methylphenyl) azetidin-2-one (IIg):      Yield 68%; mp 246oC; IR (KBr,cm-1): 3342 (-OH), 1728(C=O),1600, 1578, 1517,1448,(C=C). 1H NMR (DMSO-d6),; 2.6 (s,1H-CH), 4.25, (s,1H,CHCl), 7.20-8.22, (m,9H,Ar-H),13.2, (s,1H,Ar-OH), MS (m/z): 660(M+). Anal. Calcd for C22H15N2O4I2Cl: C,40.00, H, 2.27, N, 4.24,  Found  C, 40.05, H, 2.22, N,4.28.  3-chloro-4-(4-hydroxy-5-iodo biphenyl-3-yl)-1-(4-carboxylic-2-iodo phenyl) azetidin-2-one (IIh)      Yield 62%; mp 212oC; IR (KBr,cm-1): 3355(OH), 1738 (C=O),1725 (C=O), 1615,1600, 1550 (C=C). 1H NMR (DMSO-d6),; 2.1, (s,1H-CH), 4.2, (s,1H-CHCl), 7.3-8.3 (m,10,Ar-H),11.1(s,1H-OH), 13.2 (s,1H,Ar-OH), MS (m/z): 645(M+). Anal. Calcd for C22H14NO4I2Cl: C,40.93, H, 2.17, N, 2.17,  Found  C, 41.01; H, 2.23, N,2.22.  3-chloro-4-(4-hydroxy-5-iodobiphenyl-3-yl)-1-(2,6-dichloro-4-iodophenyl)azetidin-2-one (IIm)      Yield 72%; mp 204oC; IR (KBr,cm-1), 3320(OH), 1725 (C=O),1615,1545,1490, (C=C). 1H NMR (DMSO-d6),;  2.2 (s,1H,-CH), 4.1 (s,1H,-CHCl),7.0-8.3 (m,9H,Ar-H), 13.1 (s,1H,Ar-OH), MS (m/z): 670(M+).  Anal. Calcd for C21H12NO2I2Cl3: C,37.61, H, 1.79, N, 2.08,  Found  C, 37.68, H, 1.84; N,2.02.  Antibacterial Activity       The newly synthesized compounds were screened for their antibacterial activity using Xanthomonas citri, Escherichia coli, Erwinia Carotovora and Bacillus subtilis as bacteria. The activity of these compounds was tested by disc diffusion method [17] at 200 ppm concentration using 5mm filter disc. Penicillin was used as a standard antibiotic as control for comparison. The zone of inhibition of compounds Ic, Id, Ie, If, Ii, Ik, Im, IIc, IId, IIe, IIf, IIi, IIk and IIm were measured and it showed significant antibacterial activity. The remaining other compounds showed moderate to less activity.  RESULTS AND DISCUSSION       Structures of compounds have been elucidated by elemental analysis, IR measurements. Schiff bases shows IR absorption peak at 1615-1530 cm-1 (C=N stretching). The azetidinones were characterized by their absorption bands at 1710-1673 cm-1 (C=O stretching) of β- lactum ring and band around 1572,1563,1524 due to aromatic stretching. All the compounds show NMR signals for different kinds of protons at their respective positions. Newly synthesized compounds were screened against four bacterial pahogens. The bacteria tested were Xanthomonas citri, Escherichia coli, Erwinia carotovora and Bacillus subtilis. It is clear from results presented in table-1 that the majority of compounds tested showed antibacterial activity but compounds like Id, Ii, Ik, Im, IIi, IIk and IIm were at par against all the bacteria tested except Bacillus subtilis.  Table 1. Analytical, physical data and antibacterial activity of compounds I (a-m) and II (a-m)  Entry  Molecular formula M.P.0C Yield % Antibacterial Activity.  Xc. E.coli Ec. Bs. Ia. C19H13N2O3I2 155 80 05.00 04.00 05.03 00.00 Ib. C19H13N2O3I2  70 78 03.20 03.50 03.00 02.50 Ic. C19H13NOI2Cl  130 75 11.08  11.00  10.10 00.00 Id. C19H13NOI2Cl  110 80 20.01 21.80 19.05 00.02 Ie. C20H15NOI2  120 75 18.70 18.00 17.70 00.04 If. C19H12N2O3I2  90 70 12.00 10.00 11.20 00.02 Ig C20H15N2O3I2  160 72 07.00 06.50 06.90 00.05 Ih. C20H14NO3I2  130 78 8.50 08.02 07.20 01.90 Ii. C20H12NO3I2  180 70 20.90 21.80 20.02 00.01 Ij. C19H13N2O3I2  110 70 02.00 04.00 02.50 01.50 Ik. C20H14NO3I2 120 78 20.70 21.08 19.10 04.00 Il. C20H14NO3I2  80 82 03.50 04.00 03.50 00.02 Im. C19H12NOI2Cl2 75 80 20.00 22.00 20.50 01.00 IIa. C21H13N2O4I2Cl 234 72 05.00 00.00 05.02 00.01 IIb. C21H13N2O4I2Cl  240 85 04.00 00.00 04.08 00.04 IIc. C21H13NO2I2Cl2  214 60 16.00 15.60 16.03 01.00 IId. C21H13NO2I2Cl2  232 68 13.00 13.02 12.50 10.00 IIe. C22H15NO2I2Cl  240 65 11.00 15.00 12.00 00.00 IIf. C21H12N2O4I3Cl  256 63 10.50 09.00 10.50 06.00 IIg. C22H15N2O4I3Cl  246 68 01.00 02.00 01.00 07.00 IIh. C22H14NO4I2Cl  212 62 01.70 02.00 01.60 00.00 IIi. C22H13NO4I3Cl  260 66 20.60 21.70 18.90 05.00 IIj. C21H13N2O4I2Cl  236 68 08.20 10.00 08.50 00.00 IIk. C21H13NO2I2Cl2  244 66 20.02 21.02 19.10 00.00 IIl. C22H14NO4I2Cl  218 64 05.20 06.00 05.00 03.00 IIm. C21H12NO2I2Cl3  204 72 21.80 22.40 23.50 00.05 Penicillin (200 ppm.)    21.00 22.00 19.00 23.00  CONCLUSION       Schiff bases and 2-azetidinones have been synthesized and tested for their antibacterial activity. Some of the compounds Id, Ii, Ik, Im, IIi, IIk and IIm  were found to be nearly equal or more active than standard antibiotics used for comparison (Table 1). Hence, further study of antimicrobial activity may become fruitful.    International Multidisciplinary Research Journal 2012, 2(6):44-47  47ACKNOWLEDGEMENTS        The authors are thankful to Western Regional office U.G.C. Pune, India for sanctioning minor research grant [File No. 47-876/09 (WRO)] and the Director of IICT, Hyderabad for providing spectral analysis. The authors are also thankful to Principal, Yeshwant Mahavidyalaya, Nanded (M.S.) for providing laboratory facilities.  REFERENCES [1] Raman, N, Joseph, J, Muthukumar, S, Sujatha, S, Sahayaraj, K. J. 2008. Biopesticides. 1, 206. [2] Bharti, S.K., Nath G., Tilak R., Singh, S.K. 2010. Eur J Med Chem. 45: 651-660. [3] Solak N, Rollas S. Arkivoc 2006. xii: 173. [4] Wadher, S.J., Puranik, M.P., Karande, N.A., Yeole, P.G. 2009. Int J Pharm Tech Res. 1: 22. 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Synthesis and antibacterial activity of some new schiff bases and 2-Azetidinones containing iodohyydroxy biphenyl moiety

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Synthesis and antibacterial activity of some new schiff bases and 2-Azetidinones containing iodohyydroxy biphenyl moiety

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