antimicrobial activity against different strains of bacteria and fungi.

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1 J. Serb. Chem. Soc. 71 (6) (2006) UDC : : JSCS 3452 Note NOTE Synthesis and characterization of barbitones as antimicrobial agents H. G. SANGANI, K. B. BHIMANI, R. C. KHUNT * anda.r.parikh Department of Chemistry, Saurashtra University, Rajkot , India ( drrckhunt12@yahoo.com) (Received 22 June, revised 7 November 2005) Abstract: Barbitones (3) were synthesised by the condensation of chalcones (2) with barbituric acid. The structure of the synthesized compounds were assigned on the basis of elemental analyses, IR, NMR and mass spectral studies. All the products were evaluated for their in vitro antimicrobial activity against various strains of bacteria and fungi. Keywords: pyrazole aldehyde, chalcone, barbitones, antimicrobial activity. INTRODUCTION Nitrogen containing heterocyclic compounds, such as barbitones, are known to possess a wide range of activities, such as hypnotics, 1 cardiovascular, 2 analgesics, 3 antiviral, 4 anticancer, 5 etc. Moreover, pyrazole drugs are considered for different kinds of activities, such as antiinflammatory, 6 antiepileptic, 7 antitumor, 8 etc. These interesting biological activities attracted our attention to the chemistry of nitrogen heterocycles. Hence, it was considered of interest to determine whether the compounds resulting from the coupling of the pyrimidine ring to 1,3-diphenyl-4-formylpyrazole moiety would possess significant biological potency. The starting compound, 1,3-diphenyl-4-formylpyrazole was condensed with different aryl ketones to yield 1-aryl-3-(1,3-diphenyl-4-pyrazolyl)-2-propen-l-ones. These on condensation with barbituric acid in glacial acetic acid furnished the target molecules (Scheme 1). The constitution of all the products were characterized using elemental analyses, and IR, 1 H NMR and mass spectroscopy. All the compounds were screened for their in vitro antimicrobial activity against different strains of bacteria and fungi. EXPERIMENTAL All the melting points were determined in open capillary tubes and are uncorrected. Thin layer chromatography was used for monitoring the reaction and to check purity. The IR spectra were recorded * Corresponding author. doi: /JSC S 587

2 TABLE I. Physical constants of the compounds 3a-m Sr. R Molecular Molecular M.p. Yield % of nitrogen % of carbon % of hydrogen No. formula weight C % Calcd. Found Calcd. Found Calcd. Found 3a C 6 H 5 C 28 H 20 N 4 O b 4-Br C 6 H 4 C 28 H 19 N 4 O 3 Br c 4-Cl C 6 H 4 C 28 H 19 N 4 O 3 Cl d 4-F C 6 H 4 C 28 H 19 N 4 O 3 F e 4-CH 3 C 6 H 4 C 29 H 22 N 4 O f 4-OCH 3 C 6 H 4 C 29 H 22 N 4 O g 2-OH C 6 H 4 C 28 H 20 N 4 O h 4-OH C 6 H 4 C 28 H 20 N 4 O i 4-NH 2 C 6 H 4 C 28 H 21 N 5 O j 3-NO 2 C 6 H 4 C 28 H 19 N 5 O k 4-NO 2 C 6 H 4 C 28 H 19 N 5 O l 2-C 4 H 3 O C 26 H 18 N 4 O m 2-C 4 H 3 S C 26 H 18 N 4 O 3 S

3 SYNTHESIS OF BARBITONES 589 using a Shimadzu FTIR-8400 on KBr discs. The 1 H NMR spectra were recorded on a 300 MHz spectrophotometer using TMS as the internal standard. The FAB mass spectra were recorded on a JEOL SX 102/DA 6000 spectrophotometer. All the compounds gave satisfactory elemental analyses. 1-Aryl-3-(1,3-diphenyl-4-pyrazolyl)-2-propen-1-one (2) To a well stirred solution of 1,3-diphenyl-4-formylpyrazole (1) (2.48 g, 0.01 mol) and p-methoxyacetophenone (1.5 g, 0.01 mol) in ethanol (25 ml), 40 % NaOH was added until the solution became basic. The reaction mixture was stirred for 24 h. The contents were poured onto ice and the product was isolated and crystallized from ethanol. Yield 3.57 g (94 %), m.p. 102 o C. Anal. Calcd. for C 25 H 20 N 2 O 2 : requires: C, 78.95; H, 5.26; N, 7.36 %; found: C, 78.92; H, 5.20; N, 7.32 %. TLC solvent system: acetone/benzene (1:9); IR v max cm -1 : 2929 (C H str.); 1658 (C=O str.); 1596 (C=N str.); 1502 (CH=CH str.); 1 HNMR: ppm: 3.88 (s,3h, OCH 3 ), (m, 14H, Ar H), (d,2h,ch=ch). 5-[1-Aryl-3-(1,3-diphenyl-4-pyrazolyl)-prop-2-enylidene]barbituric acids (3) A mixture of 1-(4-metoxyphenyl)-3-(1,3-diphenyl-4-pyrazolyl)-2-propen-l-one (3.8 g, 0.01 mol), barbituric acid (1.28 g, 0.01 mol) in glacial acetic acid was refluxed for 12 h in an oil bath. The contents were poured into ice and the product was isolated and crystallized from DMF. Yield, 3.1 g (63 %), m.p. 223 o C. Anal. Calcd. for C 29 H 22 N 4 O 4 : requires: C, 71.02; H, 4.49; N, %; found: C ; H, 4.46; N, %; TLC solvent system: acetone: benzene (4:6). IR max cm -1 : 3209 (N H str.); 1739 (C=O); 1691 (C=O); 1598 (C=N). 1 HNMR: ppm: 3.86 (s, 3H, OCH 3 ), (m, 16H, Ar H & vinyl), 8.34 (s, 1H, pyrazole). MS m/z: 541 (M+2). The other barbitones were prepared in a similar maner. The physical data are given in Table I. RESULTS AND DISCUSSION Antimicrobial activity The antimicrobial activity was tested using the cup-plate agar diffusion method by measuring the zone of inhibition in mm. All the compounds were screened in vitro for their antimicrobial activity against a variety of bacterial strains, such as Bacillus megaterium, Staphylococcus aureus, Escherichia coli, Proteus vulgaris and fungi, such as Aspergillus niger at an amount of 40 mg. Known antibiotic, such as ampicillin, amoxicillin, norfloxacin, penicillin and griseofulvin were used for comparison purposes. The diameter of zone of inhibition was measured in mm. The antimicrobial screening data are recorded in Table II. Looking at the structure activity relationship, compounds, 3b, 3c, 3j, 3k,exhibit significant activity against B. megaterium, compounds 3e, 3d, 3i, 3k, 3l showed good activity against S. aureus, compounds, 3i, 3j, 3f, 3h and 3l showed

4 590 SANGANI et al. remarkable activity against P. vulgaris and E. coli, promoting activity was also observed in the case of compounds 3j, 3k, 3l to A. niger. TABLE II. Antimicrobial activity of the compounds 3a m Sr. R Antibacterial activity Antifungal activity No. Zone of inhibition/mm B. megaterium S. aureus P. vulgaris E. coli A. niger 3a C 6 H b 4-Br C 6 H c 4-Cl C 6 H d 4-F C 6 H e 4-CH 3 C 6 H f 4-OCH 3 C 6 H g 2-OH C 6 H h 4-OH C 6 H i 4-NH 2 C 6 H j 3-NO 2 C 6 H k 4-NO 2 C 6 H l 2-C 4 H 3 O m 2-C 4 H 3 S Acknowledgements: The authors are thankful to Dr. H. H. Parekh, Prof. and Head, Department of Chemistry, Saurashtra University, Rajkot for providing the research facilities. The authors are also thankful to RSIC-Chandigarh and CDRI-Lucknow for the spectral analyses. IZVOD SINTEZA I KARAKTERIZACIJA BARBITONA KAO ANTIMIKROBNIH AGENASA H. G. SANGANI, K. B. BHIMANI, R. C. KHUNT i A. R. PARIKH Department of Chemistry, Saurashtra University, Rajkot , India Kondenzacijom halkona (2) sa barbiturnom kiselinom sintetizovani su barbiturati (3). Struktura sintetizovanih jediwewa odre ena je na osnovu elementalne analize, IR, NMR i masene spektroskopije. In vitro je prou~avana aktivnost svih produkata prema razli~itim sojevima bakterija i gqivica. (Primqeno 22. juna, revidirano 7. novembra 2005) REFERENCES 1. C. I. Chappel, C. von Seeman, Prog. Med. Chem. 3 (1963) Y. K. Gupta, K. P. Bhargava, K. Shanker, J. C. Agarwal, Indian J. Chem. 20B (1981) Y. Furukawa, European Patent Appl. EP 88 (1983) 413 [C. A. 100 (1983) 22688] 4. D. Peters, A. B. Hornfield, S. Gromowitz, J. Heterocycl. Chem. 27 (1990) 2165

5 SYNTHESIS OF BARBITONES Raymond P. Daine L., Dan-Chang Wei, Wang, J. Heterocycl. Chem. 30 (1993) J. J. Talley, Shikorski, A. James, G. Matthew, C. Jaffreys; PCT. Int. Appl. WO 96 38, 418 (Cl. C07D231/12); [C.A. 126 (1997) p] 7. M. Manfred, L. Hans-Joachim, V. Klaus; Ger. Offen. DE , 822 (Cl. C07D 231/38); [C. A. 126 (1997) j] 8. L. Paolo, M. Stefano, S. Daniele, P. Alssandra; PCT. Int. Appl. WO 96 40, 704 (Cl. C07419/04), 19 Dec. 1996; [C. A. 126 (1997) b] 9. A. L. Barry, The Antimicrobial Susceptibility Test; Principle and Practice, Lea and Febiger, Philadelphia PA USA, p. 180.

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