H.S. PATEL* and H.D. DESAI Department of Chemistry, S. P. University, Vallabh Vidyanagar Gujarat (INDIA)

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1 E-Jurnal f Chemistry Vl. 1, N. 4, pp , July ynthesis f me New Azetidinne Derivatives Cntaining Aryl ulfnylxy Grup H.. PATEL* and H.D. DEAI Department f Chemistry,. P. University, Vallabh Vidyanagar Gujarat (INDIA) Received 23 April 2004; Accepted 9 June 2004 Abstract me nvel azetidinne derivatives cntaining aryl sulfnylxy grup have been prepared. The 4-sulfnylxy aniline derivative (2) has been prepared by reactin f 4-nitr phenl (sdium salt) with N-acetyl sulfanilyl chlride (AC) fllwed by hydrlysis by ethanlic HCl. This cmpund (2) underges facile cndensatin reactin with armatic aldehydes t yield different chiff s bases (3a-h). Cyclcndensatin f cmpunds (3a-h) with chlr acetyl chlride yields different 2-azetidinne derivatives (4a-h). Key wrds : New Azetidinne Derivatives, Aryl ulfnylxy Intrductin 2-Azetidines have been extensively investigated by the rganic chemists due t their clse assciatin with varius types f bilgical activities. 1-4 Azetidine-2-nes als have great imprtance because f the use f β-lactam derivatives as an antibacterial agents. 5 The antibitic activity is clsely related t the substituted β-lactam ring structure. 6 Mre particularly and recently these types f cmpunds have been fund in the treatment f T.B. and ther chemtherapeutic diseases. 7 The area in which this type f cmpund cntaining arylsulfnylxy grup (Ar 3 ) has nt received attentin in spite f well defined antibacterial activity f sulfnyl grup. 8 Hence it was thught interesting t synthesize nvel azetidinne derivatives cntaining aryl 3 grup. The present paper cmprises the synthesis and characterizatin f azetidinne derivatives as shwn in cheme 1.

2 195 H.. PATEL et al. cheme -1 2N Na + Cl NH C CH 3 1. Acetne 2. NaHC 3 3. Pyridine 2N NH C CH 3 1 Hydrlysis EtH /HCl 2N NH 2 2 CH 3 CH 2 N N = CH R 3(a-h) 1, 4 dixzne / TEA ClCCH 2 Cl H 2N N C C C H R Cl 4(a-h) Where, R= a-benzaldehyde, b-4-methyl benzaldehyde, c- 4-Methxy benzaldehyde, d- 4-Chlr benzaldehyde, e- 4- Nitr benzaldehyde, f- 4-Hydrxy benzaldehyde, g- 3,4- Dimethxy benzaldehyde, h- 3-Methxy-4-hydrxy benzaldehyde

3 ynthesis f me New Azetidinne Derivatives 196 Experimental Melting pint was taken in pen capillary tubes and are uncrrected. The synthesized cmpunds were characterized by IR spectrscpy, thin layer chrmatgraphy and elemental analyses f C,H, and N. The IR spectra were recrded in KBr pellets n a Niclet 400D spectrmeter and 1 H NMR spectra in CDCl 3 /DM n Hitachi R-1500, 60MHz spectrmeter using TM as a internal standard. TLC was perfrmed n silica gel layer and spts were visualized by expsing the develped spts and dry plates t I 2 vapurs. The required 4-acetamide benzene sulfnyl chlrides was prepared by reprted methd. 9 All chemicals used were f labratry grade. Preparatin f 4-(4 -nitrphenyl sulfnylxy) acetanilide (1) Typical prcedure dium salt f 4-nitr phenl (0.05 mle) was disslved in mixture f 40ml anhydrus acetne and 1ml f dry pyridine in 250ml R.B. flask and gm (0.05 mle) f pure 4-acetamid benzene sulfnyl chlride (AC) was added prtin wise with stirring. dium bicarbnate (0.05 mle) was added as an acid acceptr. The reactin mixture is set aside vernight and almst pure 4-(4 nitr phenyl sulfnylxy) acetanilide is filtered ff and washed with cld water and air-dried. It was then recrystalized frm ethanl t give whitish yellw prduct in 60-70% yield. Melting pint f the cmpund (1) was fund t be C. Preparatin f 4-(4-nitr phenyl sulfnylxy) aniline (2) by hydrlysis f (1) Typical prcedure The cmpund (1) was hydrlyzed by refluxing with 75ml f ethanl cntaining 15ml f cnc. HCL fr 4-5 hrs. It was then pured int ice-cld water and finally made just alkaline with liq. ammnia. The resultant hydrlyzed prduct (2) is filtered ff and washed with water and dried. It was then recrystalized frm ethanl t give prduct in 65-75% yield. Melting pint f the cmpund (2) was fund t be 105 C. Preparatin f schiff s bases (3a-h) Typical prcedure : A mixture f equimlar amunt f hydrlysis prduct (2) (0.01mle) and different armatic aldehydes (0.01mle) in 50ml acetic acid was refluxed fr abut 10hrs n il bath. The reactin mixture was cled and it was pured int ice water and the slid btained was filtered and recrystalized frm ethanl t give yellwish white prducts (3a-h) in 50-55% yield. Preparatin f Azetidinne derivatives (4a-h). Typical prcedure : A mixture f different schiff s bases (3a-h) (0.002 mle) and triethylamine (TEA) (0.004 mle) was disslved in 1,4-dixane (50 ml) and cled and stirred. T this well stirred cled slutin chlr acetyl chlride (0.004 mle) was added drp wise within a perid f 20 minute. The reactin mixture was then stirred fr further 3hrs and then refluxed fr 8 hrs. The resultant mixture was cncentrated, cled, then pured int ice-cld water and then extracted with ethyl acetate. The slvent was evaprated and the prduct thus btained was purified by clumn chrmatgraphy ver silica gel using 15% ethyl acetate: 85% benzene as eluent. Recrystallizatin frm ether/ n-hexane yields Azetidinne derivatives (4a-h) in 50-55% yield. Result and Discussin The synthesis f Azetidinne derivatives is accmplished as shwn in the cheme 1. Analytical and spectral data are given in Table 1. It was bserved that N-acetyl sulfanilyl chlride n reactin with sdium salt f 4-nitrphenl give 4-(4 nitr phenyl sulfnylxy) acetanilide (1). Its structure was established n the basis f their elemental analysis and IR spectra shwing bands at cm -1 ( 3 ) and 1550 cm -1 (CNH). Cmpund (1) was easily hydrlyzed 10 with EtH/HCl t give cmpund (2). The hydrlyzed prduct (2) have cnsistent value f C.H.N and cntents with predicated structure. Als cmpund (2) shws the diaz test fr primary amine (-NH 2 ) grup. The IR spectra f (2) shw absrptin bands at 3390 & 3410 cm -1 (NH 2 ) and cm -1 (- 3 ). The cmpund (2) was als cnfirmed by 1 HNMR spectra shwing peaks f NH 2 at 4.20 and fr armatic prtns.

4 197 H.. PATEL et al. Table 1 Analytical and pectral data f Cmpunds (4a-h) Cmps 4a 4b 4c Mlecular frmula C 21 H 15 6 N 2 Cl C 22 H 17 6 N 2 Cl C 22 H 17 7 N 2 Cl 4d C 21 H 14 6 N 2 Cl 2 4e 4f 4g 4h C 21 H 14 8 N 3 Cl C 21 H 15 7 N 2 Cl C 22 H 17 8 N 2 Cl C 23 H 19 8 N 2 Cl % Analysis Calculated (Fund) %C %H %N (54.85) (55.75) (53.95) (51.10) (49.90) (52.95) (52.20) (53.15) 3.20 (3.10) 3.59 (3.50) 3.48 (3.35) 2.84 (2.75) 2.78 (2.65) 3.16 (3.05) 3.36 (3.25) 3.66 (3.55) Yield % M.P. 0 C 6.10 (6.05) (5.80) 5.73 (5.65) 5.69 (5.55) 8.34 (8.25) 5.90 (5.75) 5.55 (5.45) 5.40 (5.30) PMR (δ,ppm)( (13H,m,armatic) 1.9 (3H,s,CH 3 ) (1H,d, C 4 H), (1H,d,C 3 H), (12H,m,armatic) 2.9 (3H,s,CH 3 ) (1H,d,C 4 H), (1H,d,C 3 H), (12H,m,armatic) (1H,d,C 4 H), (1H,d,C 3 H), (12H,m,armatic) (12H,m,armatic) 3.9 (1H,hump,H) (1H,d,C 3 H), (12H,m,armatic) 2.9 (3H,s,CH 3 ), 3.8(1H,hump,H), (11H,m,armatic) 3.1 (6H,s,2CH 3 ) (1H,d,C 4 H), (11H,m,armatic) The abve cmpund (2) n cndensatin with different armatic aldehydes in acetic acid yielded different schiff s bases (3a-h). The structures f (3a-h) were cnfirmed, by elemental analysis and the IR spectra shwing absrptin band at (-C=N). The cyclcndensatin reactin f cmpunds (3a-h) with chlr acetylchlride in dry dixne in presence f triethylamine (TEA) as catalyst resulted in frmatin f 2-azetidinnes 11 (4a-h). The structure assigned t (4a-h) were supprted by elemental analyses and IR spectra shwing absrptins bands at (C= 0 f mncyclic -lactam). The structures were als cnfirmed n the basis f 1 HNMR spectrum. Acknwledgement The authrs are thankful t Dr. R.M. patel, Head, Department f Chemistry fr prviding labratry facilities.

5 ynthesis f me New Azetidinne Derivatives 198 Reference 1. Ra J, renivasulu B and Mgilaiah K, Indian J. Chem., 1995, 34B, Kidwai M, Bala R and Kumar K, Indian J. Pharm. ci., 1995, 57, Hartmann H, Czerney P and Liebscher J, Chem. Asrtr., 1984, 101, Feng X, Chem R and Lin T, Yuji Huxaxue, 1994, 14, 293, Chem. Abstr., 1994, 121, Kppel G A, mall ring Hetrcycles, Wiley Intersciences, New Yrk, Clarke H T, Jhnsn J R and Rbinsn R, The Chemistry f Penicillin, Princetn University Press, Princetn, Vashi B, Mehta D and hah V H, Indian J. Chem., 1994, 34B, hepherd R G, ulfanilamides and ther p-amin-benzic acid antagnists. Medicinal Chemistry, Vl. I, edited by A. Burger, Wiley interscience, Trnt, 1969, Vgel A I, A Textbk f Practical rganic Chemistry, 4 th editin, Vgel A I, A Textbk f Practical rganic Chemistry, 4 th editin, 1978, harma P, Indapurkar P and Mandli A, Indian J. Chem, 1998, 37B, 521.

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