Read Microsoft Word - IJCB 44B_7_ 1452-1455.doc text version

Indian Journal of Chemistry Vol. 44B, July 2005, pp. 1452-1455

Synthesis of pyrazole imines and azetidinone compounds using conventional and microwave technique and studies of their antibacterial activity

Ketan Mistry* & K R Desai

Department of Chemistry, South Gujarat University, Surat 395007, India. Received 24 March 2004; accepted (revised) 17 November 2004 A series of compounds 4-[spiro-{1-(4-methylphenyl)-3-methyl}-pyrazole]-3-chloro-1-(substitutedbenzothiazole)-2azetidinone 4a-j have been prepared by the reaction of 1-(4-methylphenyl)-3-methyl-5-(2-iminosubstitutedbenzothiazole)pyrazoles 3a-j with chloroacetyl chloride in the presence of triethylamine. The pyrazole derivatives 3a-j have been prepared by the condensation of substituted 2-aminobenzothiazole 1 with 1-(4-methylphenyl)-3-methyl-5-pyrazolone 2. Both the reactions have been carried out by conventional and microwave methods. The synthesized compounds are screened for their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella typhi. Keywords: Pyrozole imines, azetidinone, pyrazoles, chloroacetyl chloride, 2-aminobenzothiazole, pyrazolone, microwave methods, antibacterial activity IPC: Int.Cl.7 C 07 D 277/02

Benzothiazole derivatives play a vital role in biological fields as anti-TB1 and anti-allergic activity. Some pyrazole derivatives possess analgesic2, antiinflammatory3, antibacterial4 and hypoglycemic5 activity. Schiff base has good antimicrobial, fungicidal6 and pharmacological applications7 and it can be prepared by the acid catalyzed reaction of amines and ketones or aldehydes. 2-Azetidinone derivatives have been reported to possess antiinflammatory, antidegenerative, fungicidal8 and antibiotic9 activity. The application of microwave irradiation is used for carrying out chemical transformations which are pollution free and eco-friendly10,11. Commercial microwave oven is used as a convenient source of heat in the laboratory. The microwave assisted organic reactions occur more rapidly, safely and with higher chemical yields12,13, render the microwave method superior to conventional method. The starting compounds substituted 2-aminobenzothiazoles 1a-j have been synthesized from various substituted amines14. The condensation of 1a-j with 1-(4-methylphenyl)-3-methyl-5-pyrazolone 2 was carried out by both conventional and microwave methods to give compounds 1-(4methylphenyl)-3-methyl-5-(2-iminosubstitutedbenzothiazole)pyrazoles 3a-j. In conventional method, the reaction was carried out in methanol and it took 5-6

hr, whereas by microwave irradiation it took only 2-3 min15. In conventional method treatment of the pyrazolines 3a-j with chloroacetyl chloride in the presence of triethylamine using benzene as a solvent yielded compounds 4-[spiro-{1-(4-methylphenyl)-3-methyl}pyrazole]-3-chloro-1-(substitutedbenzothiazole)-2-azetidinones 4a-j (Scheme I). It took about 15-16 hr, while under microwave irradiation using DMF as a solvent the reaction was complete in 3-4 min. A comparative study in terms of yield and reaction period is shown in Table I and Table II. Experimental Section All the melting points were determined in open capillaries and are uncorrected. The purity of compounds was checked by TLC on silica gel `G' coated glass plates. IR spectra were recorded in KBr on Shimadzu FT-IR 8300 spectrophotometer; 1H NMR spectra in CDCl3 on a Brucker DRX-300 at 200 MHz using TMS as an internal standard. Microwave assisted reactions were carried out in a BPL 2300 ET domestic microwave oven. Synthesis of 1-(4-methylphenyl)-3-methyl-5-(2imino-6-nitrobenzothiazole)pyrazole 3a Conventional method. A mixture of 2 (0.01 mole, 1.88 g) and 2-amino-6-nitrobenzothiazole 1a

MISTRY et al.: SYNTHESIS OF PYRAZOLE IMINES AND AZETIDINONES BY MWI

1453

O C R S

1

CH3

N NH2 Conventional 5 - 6 hr. Methanol N S

+

H3C Microwave 2 - 3 min.

2

N N

R

N C N N

CH3

H3C

3

ClCH2COCl Conventional, 15 - 16 hr, Benzene TEA Microwave, 3 - 4 min, DMF O R S N N C N N

3,4 f g h i j R 6-Cl 4,6-(NO2)2 6-OCH3 4-NO2 6-NHCOCH3

Cl CH3

H3C

3,4 a b c d e R 6-NO2 6-SO3H 6-CH3 6-OH 4-OCH3

4

Scheme I

(0.01 mole, 1.95 g) was taken in round bottom flask and to it 20 mL methanol was added and the mixture refluxed for 5-6 hr. After the completion of reaction, some amount of the solvent was removed by vacuum distillation. The crude product obtained was recrystallised from absolute alcohol, m.p. 128 oC, yield 75%. Microwave method. A mixture of 2 (0.01 mole, 1.88 g) and 1a (0.01 mole, 1.95 g) was taken in a conical flask and to it 20 mL of methanol was added and the reaction mixture was put outside the microwave oven to evaporate methanol and the remaining mixture was placed inside a microwave oven for about 2-3 min. The mixture was then cooled in an ice-bath. The product formed was filtered,

washed with water, dried and recrystallised from absolute alcohol, m.p. 128 oC, yield 90%. Following the same procedure, compounds 3b-j were prepared. Their characterization data are recorded in Table I. Synthesis of 4-[spiro-{1-(4-methylphenyl)-3methyl}pyrazole]-3-chloro-1-(6-nitrobenzothiazole)-2-azetidinone 4a Conventional method. A mixture of 3a (0.01 mole, 3.65 g) in benzene was taken in a 50 mL round bottom flask. To it chloroacetyl chloride (0.01 mole, 1.12 g) and triethylamine (0.01 mole, 1.01 g) in benzene were added slowly. It was refluxed for 1516 hr. The triethylamine hydrochloride formed during

1454

INDIAN J. CHEM., SEC B, JULY 2005 Table Characterization data of compounds 3a-j Compd m.p. °C 128 Yield (%) (period/hr) Conventional method Yield (%) (period/min) Microwave method Mol. formula (Mol. wt) Found (Calcd) (%) C H N

75 90 C18H15N5O2S 59.17 4.10 19.17 (5.0) (2.0) (365.41) (59.20 4.12 19.20) 54.00 4.00 14.00 125 70 87 C18H16N4O3S2 3b (400.47) (54.02 4.04 14.03) (5.0) (2.0) 98 67 82 C19H18N4S 68.26 5.38 16.76 3c (5.5) (2.0) (334.43) (68.24 5.35 16.75) 119 75 85 C18H16N4OS 64.28 4.76 16.66 3d (5.5) (1.5) (336.41) (64.31 4.79 16.69) 65.14 5.14 16.00 97 70 85 C19H18N4OS 3e (350.43) (65.11 5.18 16.02) (5.0) (2.5) 115 60 88 C18H15N4SCl 60.93 4.23 15.79 3f (6.0) (2.5) (354.85) (60.96 4.24 15.81) 52.68 3.41 20.48 123 62 80 C18H14N6O4S 3g (410.40) (52.70 3.43 20.50) (5.5) (2.0) 99 70 90 C19H18N4OS 65.14 5.14 16.00 3h (6.0) (1.5) (350.43) (65.11 5.11 16.04) 111 75 83 C18H15N5O2S 59.17 4.10 19.17 3i (6.5) (2.5) (365.41) (59.20 4.13 19.14) 121 70 85 C20H19N5OS 63.66 5.03 18.56 3j (6.0) (2.5) (377.46) (63.70 5.05 18.59) 3a: 1H NMR: 2.3 (3H, s, Ar-CH3), 3.08 (2H, s, -CH2), 1.95 (3H, s, -CH3), 7.00-7.23 (7H, m, Ar-H) 3c: 1H NMR: 2.35 (6H, s, Ar-CH3), 3.12 (2H, s, -CH2), 1.98 (3H, s, -CH3), 6.95-7.18 (7H, m, Ar-H) 3e: 1H NMR: 2.38 (3H, s, Ar-CH3), 3.01 (2H, s, -CH2), 2.02 (3H, s, -CH3), 2.82 (3H, s, -OCH3) 7.11-7.38 (7H, m, Ar-H) 3f: 1H NMR: 2.24 (3H, s, Ar-CH3), 3.11 (2H, s, -CH2), 2.05 (3H, s, -CH3), 7.21-7.51 (7H, m, Ar-H) 3i: 1H NMR: 2.1 (3H, s, Ar-CH3), 3.10 (2H, s, -CH2), 2.0 (3H, s, -CH3), 6.96-7.32 (7H, m, Ar-H) 3a Table II Characterization data of compounds 4a-j Compd m.p. °C 180 220 119 149 112 163 138 122 129 170 Yield (%) (period/hr) Conventional method 65 (15.0) 60 (15.0) 62 (16.0) 60 (15.0) 60 (15.0) 62 (16.0) 65 (16.0) 58 (15.0) 55 (15.0) 65 (16.0) Yield (%) (period/min) Microwave method 82 (4.0) 80 (3.5) 85 (3.5) 85 (3.5) 79 (3.0) 75 (3.5) 80 (3.5) 75 (3.0) 70 (4.0) 80 (4.0) Mol. formula (Mol. wt) C20H16N5O3SCl (441.89) C20H17N4O4S2Cl (476.95) C21H19N4OSCl (410.92) C20H17N4O2SCl (412.89) C21H19N4O2SCl (426.92) C20H16N4OSCl2 (431.33) C20H15N6O5SCl (486.88) C21H19N4O2SCl (426.92) C20H16N5O3SCl (441.89) C22H20N5O2SCl (453.94) Found (Calcd) (%) C H N 54.36 (54.39 50.36 (50.38 61.38 (61.35 58.15 (58.19 59.08 (59.11 55.68 (55.66 49.33 (49.36 59.08 (59.07 54.36 (54.34 58.21 (58.25 3.62 3.65 3.56 3.58 4.62 4.66 4.12 4.10 4.45 4.48 3.70 3.74 3.08 3.05 4.45 4.47 3.62 3.60 4.41 4.44 15.85 15.88) 11.75 11.72) 13.64 13.66) 13.57 13.60) 13.13 13.10) 12.97 12.99) 17.26 17.28) 13.13 13.11) 15.85 15.88) 15.43 15.47)

4a 4b 4c 4d 4e 4f 4g 4h 4i 4j

4c: 1H NMR: 2.29 (6H, s, Ar-CH3), 3.08 (2H, s, -CH2), 1.9 (3H, s, -CH3), 6.86-7.11 (7H, m, Ar-H), 3.45 (1H, s, -CH) 4d: 1H NMR: 2.31 (3H, s, Ar-CH3), 3.13 (2H, s, -CH2), 1.98 (3H, s, -CH3), 7.12-7.41 (7H, m, Ar-H), 3.56 (1H, s, -CH), 9.2 (1H, s, -OH) 4f: 1H NMR: 2.35 (3H, s, Ar-CH3), 3.05 (2H, s, -CH2), 2.01 (3H, s, -CH3), 7.02-7.32 (7H, m, Ar-H), 3.35 (1H, s, -CH) 4g: 1H NMR: 2.39 (3H, s, Ar-CH3), 3.16 (2H, s, -CH2), 2.05 (3H, s, -CH3), 7.18-7.47 (6H, m, Ar-H), 3.62 (1H, s, -CH) 4h: 1H NMR: 2.25 (3H, s, Ar-CH3), 3.13 (2H, s, -CH2), 2.00 (3H, s, -CH3), 6.95-7.37 (7H, m, Ar-H), 3.77 (1H, s, -CH), 2.70 (3H, s, -OCH3)

MISTRY et al.: SYNTHESIS OF PYRAZOLE IMINES AND AZETIDINONES BY MWI

1455

Table III Zone of inhibition (mm) of compounds 3a-j and 4a-j Compd 3a 3b 3c 3d 3e 3f 3g 3h 3i 3j 4a 4b 4c 4d 4e 4f 4g 4h 4i 4j Ampicillin Penicilline Tetracycline S. aureus 10.0 11.0 9.0 10.0 11.0 9.0 8.0 12.0 7.0 11.0 11.0 10.0 7.0 9.0 12.0 8.0 10.0 9.0 10.0 11.0 12.0 13.0 15.0 B. subtilis 12.0 10.0 9.0 8.0 9.0 9.0 10.0 11.0 7.0 9.0 10.0 12.0 8.0 10.0 9.0 7.0 8.0 12.0 9.0 7.0 14.0 16.0 13.0 E. coli 9.0 12.0 7.0 9.0 10.0 10.0 9.0 11.0 10.0 9.0 10.0 10.0 7.0 8.0 10.0 7.0 12.0 11.0 8.0 10.0 11.0 12.0 16.0 S. typhi 8.0 10.0 8.0 11.0 12.0 7.0 11.0 10.0 8.0 12.0 12.0 8.0 9.0 7.0 9.0 11.0 7.0 12.0 10.0 8.0 13.0 14.0 17.0

inhibition on agar plates (diffusimetric method)16 with Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella typhi as test organisms. The results of antibacterial screening indicated that good activity was shown by compounds 3b, 3e, 3h, 3j, 4a, 4e, 4j against S. aureus, compounds 3a, 3h, 4b, 4h against B. subtilis, compounds 3b, 3e, 3h, 4b, 4g, 4h against E. coli and compounds compounds 3d, 3e, 3g, 3j, 4a, 4f, 4h showed good activity towards S. typhi. While compounds 3g, 3i, 4c, 4f were less active against S. aureus, compounds 3d, 3i, 4c, 4f, 4g, 4i against B. subtilis, compounds 3c, 3g, 4c, 4f, 4i against E. coli and compounds 3a, 3c, 3f, 3i, 4b, 4d, 4g, 4j were less active against S. typhi. Other compounds showed moderate activity against both bacterial strains (Table III). Acknowledgement The authors are thankful to the South Gujarat University, Surat for providing research facilities and to CDRI, Lucknow for providing 1H NMR spectra and elemental analysis. References

1 Cox O, Jackson H & Vargas V A, J Mednl Chem, 25, 1982, 1378. 2 Sheng chu kno, Li Jiau Huang & Hideo Nakamura, J Mednl Chem, 27, 1984, 539. 3 Winters G, Sala A, Borone D & Baldoli E, J Mednl Chem, 28, 1985, 934. 4 Subbanwad G R & Vibhute Y B, J Indian Chem Soc, 69, 1992, 781. 5 Saharia G S & Sharma H R, J Indian Chem Soc, 51, 1974, 351. 6 Dash B, Mahapatra P K, Panda D & Patnaik J M, J Indian Chem Soc, 61, 1984, 1061. 7 Warad D U, Satish C D, Kulkarni V H & Bajgur C S, Indian J Chem, 39A, 2000, 415. 8 Giri S & Khan M, J Indian Chem Soc, 71, 1994, 201. 9 Akiba K & Wada M, Chem Abstr, 111, 1989, 96964b. 10 Kidwai M, Chem Edu Rev, 15(4), 2000, 34. 11 Srivastava K P, Res J Chem Environ, 5(2), 2001, 77. 12 Michael D, Chem Soc Rev, 20(1), 1991, 1. 13 Mogilaiah K, Reddy N V & Reddy P R, Indian J Heterocycl Chem, 10, 2001, 267. 14 Ojha K G, Tahiliani Heer & Jaisinghani Neera, Indian J Chem, 42B, 2003, 171. 15 Villemin D, Synthetic Commun, 20(20), 1990, 3213. 16 Weber A D & Sanders C S, Antimicrob Agents Chemother, 34, 1990, 156.

the reaction, was removed and the benzene was distilled off to get the product. The crude product obtained was recrystallised from ethanol, m.p. 180 oC, yield 65%. Microwave method. A mixture of 3a (0.01 mole, 3.65 g) in DMF was taken in a conical flask, and chloroacetyl chloride (0.01 mole, 1.12 g) and triethylamine (0.01 mole, 1.01 g) were added slowly. The mixture was irradiated in a microwave oven for about 3-4 min. It was then diluted with ice-cold water. The solid product thus formed was filtered, dried and recrystallised from ethanol, m.p. 180 oC, yield 82%. Following the same procedure, the compounds 4b-j were prepared. Their characterization data are recorded in Table II. Antibacterial activity The synthesized compounds were tested for their antibacterial activity by measuring the zone of

Information

Microsoft Word - IJCB 44B_7_ 1452-1455.doc

4 pages

Report File (DMCA)

Our content is added by our users. We aim to remove reported files within 1 working day. Please use this link to notify us:

Report this file as copyright or inappropriate

680212


You might also be interested in

BETA
untitled
Microsoft Word - IJCB 44B_7_ 1452-1455.doc
358_362
Reference list 1-14-09.xls
Microsoft Word - AJRC_4_10_2011_Abstract