Evalution of Some New 2-Isothiazoline Derivatives from Chalcone and their Antibacterial Activity

Evalution of Some New 2-Isothiazoline Derivatives from Chalcone and their Antibacterial Activity

Dr. Sunil M. Naik

I/C Principal, Naran Lala College of Professional & Applied Sciences, Navsari.

Abstract – 2-isothiazoline derivatives can be synthesized from the chalcone by the action of hydroxyl amine hydrochloride which was followed by the reaction with phosphorous penta sulphide. These all synthesized derivatives of 2-isothiazoli have been screened for antibacterial activity and characterized by spectral studies.

Keywords: 2-hydroxy-5-methyl-4,6-dibromoacetophenone, Substituted aldehyde, Chlcones, 2-isoxazolines,2-isothiazoline, Antibacterial activity, IR/NMR Spectroscopy.

INTRODUCTION

Chalcone have many pharmacological activity such as antimicrobial1, antiviral2, anti-inflammtory3, antifungal4, antispasmodics5, etc Various chalcones derivatives can be obtained by the condensation of aryl ketone with the various substituted aldehyde6,7. Chalcone and its related hetero cyclic derivatives such as isothiazoline, oxazine, pyrazoline, isoxazole, thiazine, pyrimidine, benzthiazepine, quinoxaline etc shows antibacterial activity against various gram positive and gram negative bacteria8-12. We report the reaction of 2- hydroxy-5-methyl-4,6-dibromoacetophenone with various substituted aromatic aldehydes to produced corresponding 2-hydroxy-5-methyl-4,6-dibromo chalcones[1A-1J]. Which on treatment with hydroxyl amine hydrochloride gives 2-isoxazoline derivative[2A-2J] and finally reaction with phosphorous pentasulphide produced 2- isothiazoline derivatives[3A-3J]. The constitution of all compounds synthesized was characterized by elemental analysis, IR and H1 NMR spectral study.

Compounds were also evaluated for antibacterial activity.

MATERIAL AND METHODS

All melting points were taken in open capillary tubes and are uncocorrected. IR spectra in KBr were recorded on perkin-Elmer-377 spectrophotometer and H1 NMR spectra were recorded on Varian NMR

spectrophotometer. All compounds gave satisfactory elemental analysis.

General method for the synthesis of 2-hydroxy-5-methyl- 4,6-dibromo chalcones[1A-1J]

A mixture of 2-hydroxy-5methyl-4,6- dibromoacetophenone (0.01 mole) and aryl aldehyde (0.01 mole) in ethanol (30 ml) was stirred and to it excess of 40% potassium hydroxide (25 ml) solution was added. The mixture was kept overnight at room temperature. The colour of the reaction mixture was change from yellow to orange. The content was then poured over crushed ice and acidified with hydrochloric acid (1:1). The solid separated was filtered, washed with distilled water, dried and crystallized from ethanol, yield 60-70%.

General method for the synthesis of 3-(2-hydroxy-5- methyl-4,6-dibromophen-1-yl)-5-(substituted phenyl)-2- isoxazoline[2A-2J]

A mixture of 2-hydroxy-5-methyl-4,6- dibromo chalcone (0.01 mol) and hydroxylamaine hydrochloride (0.02 mol) in ethanol (25 ml) was refluxed on water bath at 60-70°C for 4 hours. The reaction was cooled and acidified with glacial acetic acid. The solid separated was filtered and washed with water, dried and crystallized from ethanol (99%), yield 40-50%.

General method for the synthesis of 3-(2-hydroxy-5- methyl-4,6-dibromophen-1-yl)-5-(substituted phenyl)-2- isothiazoline[3A-3J]

A mixture of 3-(2-hydroxy-5-methyl-4,6- dibromophen-1-yl)-5-(substituted phenyl)-2-isoxazoline (0.01 mol) and phosphorous pentasulphide (0.01 mol), was taken in pyridine (20 ml). The reaction mixture was refluxed on water bath at 80-90°C for an hour. The reaction mixture was then cooled and diluted with water. The solid obtained was filtered, washed with water and crystallized from ethanol (99%), yield 40-60%.

REACTION SCHEME

Br OH

+ OHC-R

40% KOH

ethanol

Br OH

H3C

C CH3

Br O

H3C

C CH CH R

Br O

2-hydroxy-methyl-4,6-dibromoacetophenone Substituted aldehydes Chalcones

Br OH

NH2OH.HCl C H OH/KOH

Br OH

R

H3C

2 5

C CH CH R

Br O

H3C

Br N O

P2S5

Pyridine

Br OH

H3C

R

Br N O

Where R = 4-chlorophenyl, 4-hydroxyphenyl, Phenyl, 2,4-dichlorophenyl, 3-phenoxyphenyl, 2,6-dichlorophenyl, 3-nitrophenyl, 3,4,5-trimethoxyphenyl, 4-methoxyphenyl, 4-N,N-dimethylaminophenyl.

SCHEME TABLE- 1

Characterization Table of 3-(2-hydroxy-5-methyl-4,6-dibromophen-1-yl)-5-(substituted phenyl)-2-isothiazoline[3A-3J]

1H NMR Spectroscopy

Nuclear magnetic resonance (NMR) spectroscopy is one of the latest physical methods which is use for the structure determination of organic compounds. PMR spectra of 2-isothiazoline derivatives were recorded on varian spectrophotometer. Spectra were examined in CDCl3 at room temperature using TMS as internal standard.

TABLE-2

200 MHz PMR spectra of 3-(2-hydroxy-5-methyl-4,6-dibromophen-1-yl)-5-(4methoxyphenyl)-2-isothiazoline ( Compound no. 3I)

Chemical shift Relative Number of Protones Assignment

Infrared spectra

Infrared absorption were recorded using potassium bromide pallets method. The spectra were recorded using Perkin- Elmer spectrophotometer. The results are describe in table no. 3.

TABLE-3

IR spectra of 3-(2-hydroxy-5-methyl-4,6-dibromophen-1-yl)-5-(4chlorophenyl)-2-isothiazoline ( Compound no. 3A)

S=strong, m=medium, b=broad, w=weak, sh=sharp, v=variable

Antibacterial activity

The synthesized compounds were screened for their antibacterial activity using S.aureus, E. coli by cup plate method using DMF as solvent. All the compounds shows mild activity against both bacteria in comparison with ampicilin and gentamycin. The results are describe in table no. 4.

Table-4

Compound No. Zone of inhabitation in mm Antibacterial (24 hrs.)

2-isothiazoline derivatives shown medium activity against both bacteria i.e. S.aureus and E.coli. From the table no. 4, compound no. 3I shown the maximum activity amongst all the compounds towards ve bacteria i.e. E.coli. The compound no. 3D and 3G haven shown good activity against S.aureus bacteria. The compound no. 3E found inactive against both bacteria while rest of the compounds have shown the medium to poor activity against both

compared with standard antibiotics like Ampicillin and Gentamicin. It was observed that the synthesized compounds are less active than the standard one.

ACKNOWLEDGEMENT

The authors are thankful to Department of Chemistry,

REFERENCES

1. Y. B. Vibhute; Indian J. Chem. Soc., 53, 736 (1976); C.A. 86, 106308 (1977).

2. K.G.Mallikarjun; E-Journal of Chemistry, 2(1), 58 -61 (2005).

3. Y. R. Prasad, A. Srinivasa Rao And R. Rambabu; Asian Journal of Chemistry, 21(2), 907-914 (2009).

4. C. K. Bradsher, F. C. Brown, and W. B. Blue; Am. Chem. Soc., 71, 3570 (1949).

5. S. Oshiro, T. Nagura, Y. Sugihara, K. Okamoto, R.Ishida and K. Shintomi; Japanese Patent, 73 19,569, 19,594 (1973); C.A. 78, 147788g, 147790b, 147963k (1973).

6. G. N. Vyas and N. M. Shah; Indian J. Chem. Soc., 28, 75 (1951).

1. Chinna Rao Gantla, Y.Suresh, S.Harikrishana And S.P. Shrivastava; Oriental Journal of Chemistry, 25(1), 153-157 (2009).

2. V.M. Barot And S.D. Desai; Asian Journal Of Chemistry, 21(8), 6091-6094 (2009).

3. R. Kalirajan, S. U. Sivakumar, S. Jubie and B. Gowramma, B. Suresh, Int. J. Chem. Tech. Res., 1(1), 27-34 ( 2009).

4. K. G. Desai and K. R. Desai; Indian Journal of Chemistry, 46B, 1179-1186 (2007).

5. M. Kaithwal, P. Garg and S. Ahmad, Orient. J. Chem., 25(4), 935- 943 (2009).