IJRPC 2012, 2(1) Vidyashri et al ISSN: 22312781
INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY
Available online at www.ijrpc.com Research Article
SYNTHESIS AND EVALUATION OF 4-(1- BENZOFURAN-2- YL)-1,3-OXAZOLE-2-AMINE AND ITS DERIVATIVES Vidyashri S. Kamble1*, Bhalchandra M. Habade1, Geeta K. Patil2 and Y. Agasimundin2 1Shivajirao S. Jondhale College of Pharmacy, Aasangaon, Dist. Thane, Maharashtra, India. 2 B.L.D.E.A’s College of pharmacy, Bijapur, Karnataka, India.
ABSTRACT Salicylaldehyde upon treatment with chloroacetone in presence of anhydrous potassium carbonate give 2-acetylbenzofuran.This 2-acetylbenzzofuran after chlorination gives chloroacetylbenzofuran. This chloroacetylbenzofuran on treatment with urea in ethanol gives 4 (1-benzofuran-2-yl) 1, 3-oxazole-2-amine.The corresponding compound on treatment with
various aldehydes to give different derivative. The characterization of synthesized compounds was identified on the basis of IR, NMR, MASS and elementary analysis. The compound has been
evaluated for anti-bacterial activity. The present study is focused on the development of new
potent bioactive molecule with less toxic, safer and easy available. Modern therapeutic is based
on scientific observation supported by systematic assessment of activity of drug is simulated and clinical condition.
Keywords: chloroacetone, 2-acetylbenzofuran, chlorination, Salicylaldehyde.
INTRODUCTION discovered benzofuran in coal tar. It was Benzofuran nucleus may be combined with synthesized by Perkin in 1870. Thus the nitrogen heterocycle in different ways. Several chemistry of benzofuran has developed in a benzofuran compounds are reported to posses, spectacular fashion during the last several antibacterial, antifungal, Anti-inflammatory, years. antidepressant, analgesic and hypoglycemic activities. It has already been pointed out that MATERIAL AND METHODS benzofuran nucleus is very rarely associated The entire chemical used was purchase from with a nitrogen heterocycle. Several isoxazole Qualingens, Himedia and Loba-chemicals. derivatives are found to possess antitubercular, Purity of starting materials used for reaction was antimicrobial and anti-inflammatory activities. confirmed by checking their melting point or The benzofuran nucleus and derivatives occupy boiling point and by thin layer chromatography. apposition of considerable significance for Purity of compounds was checked on precoated widespread occurrence in plants and their plates, eluent was the mixture of different polar potential as important pharmaceuticals. This fact and non-polar solvents in varying proportions created interest in synthetic products containing and detection was done either by observing in benzofuran nucleus. Kreamer and Spilker UV (ultra-violet) light or exposure to iodine 32
IJRPC 2012, 2(1) Vidyashri et al ISSN: 22312781 vapours as required.The products of all the 20mlabsolute ethanol. to this add 1gm of . 4-(1- reactions were purified initially by different benzofuran-2-yl)-1, 3-oxazole-2-amine to this workup process to remove unreacted starting solution add equimolar amount of different materials if any and then by recrystallization aromatic aldehydes reflux for 7-8 hr. The using suitable solvent. The absence of any resultant reaction mixture was cooled, poured impurity of starting materials or possible by into the ice-cold water. The solid separated was product was ensured by performing qualitative filtered and dried. The solid was recrystalized organic analytical tests for various functional into ethanol. groups. Anti-bacterial activity14 Synthesis of 2-Acetyl Benzofuran (I) 1-3 Preparation of Test Solution In completely dried round bottom flask 12.2 ml of 10 mg of the compound was dissolved in 10 ml Salicylaldehyde was taken then it is charged of DMSO. From this 2 ml of solution was taken with chloroacetone (8.3 ml) with addition of 150 and diluted up to 10 ml with DMSO. Now the ml anhydrous acetone to this reaction mixture 35 concentration of the test solution was 200 µg/ml. gm of anhydrous acetone was added. Round bottom flask was attach to condenser and reflux Preparation of Standard Solution for 10 hr. in water bath by maintaing Amoxicillin was used as standard antibiotic for temperature for reflux and stirred it continuously. comparison and solutions were prepared by After 10 hr reaction mixture cooled to room using sterile water, as they were water soluble. temperature and filtered by funnel to get clear The solutions are diluted by using sterile water solution then 10-15 ml acetone was used to so that the concentration of the solutions was wash potassium carbonate filtrate was taken in 200 µg/ml. dry flask and acetone was removed by vaccum pump crystallization was achieved by petroleum Preparation of Discs ether on hot plate. Discs of 6-7 mm in diameter were punched from Melting point of 2-acetylbenzofuran = 790C NO: 1 Whattmann filter paper with sterile cork borer of same size. These discs were sterilized Synthesis of bromoacetylbenzofuran (II) 4-6 by keeping in oven at 1400c for 60 minutes. A solution of bromine (12 gm 0.075 mole)in Then standard and test solutions were added to acetic acid (100ml) was added drop wise with each disc and discs were air-dried. stirring to a solution of 2-acetylbenzofuran (12gm, 0.075 mole) in acetic acid (100ml). After Method of Testing complete addition of bromine, the mixture was The sterilized media was cooled to 450 C with stirred for 45 min and allowed to stand for 30 gentle shaking to bring about uniform cooling min. then the mixture was decanted in crushed and then inoculated with 18-24 hrs old culture ice, the solid separated was collected and under aseptic conditions, mixed well by gentle crystallized from ethanol as light green crystals shaking. This was poured in to sterile Petri MP =940 C. dishes (properly labeled) and allowed the medium to set. After solidification all the Petri Synthesis of 4-(1-Benzofuran-2-Yl)-1,3- dishes were transferred to laminar flow unit. oxazole-2-Amine (III) 7-10 Then the discs which were previously prepared A Solution of 2-brmoacetylbenzofuran (11.95gm, were carefully kept on the solidified media by 0.05 mole) and urea(3.5gm, 0.05mole) was using sterilized forceps. These Petri dishes were refluxed in ethanol (250 ml) for 2hrs. the reaction kept as it is for one-hour diffusion at room mixture was then cooled, poured in to cold water temperature and then for incubation at 370C for and neutralized with 5% aqueous sodium 24 hours in an incubator. The extent diameter of acetate. The solid thus obtained was collected inhibition after 24 hours was measured as the and recrystalized from ethanol as colorless tiny zone of inhibition in millimeters. crystals. RESULT AND DISCUSSION General Procedure for Preparation of 4-(1- All the reactions were monitored by TLC, Benzofuran-2-yl)-1,3-oxazole-2-Amine structures and purity of the anticipated Derivatives (IIIa-b) compounds were characterize by physical In two necked round bottom flask take constant and FTIR spectral studies initially 33
IJRPC 2012, 2(1) Vidyashri et al ISSN: 22312781 followed by 1H-NMR and Mass spectroscopy 1080 thus confirming the formation of 2-Acetyl Absence of TLC spots for starting materials and benzofuran. The FT-IR in KBr (cm-1) spectra of appearance of new TLC spot at different Rf compound 4 showing bands at 1583.23 (Ar-CH), value were ensured to declare completion of 1088 (C-O-C), 828.42 (C-Br), 1345. The FT-IR reaction. The TLC plates were visualized either in KBr (cm-1) spectra of compound 5 showing a by Iodine vapours or by viewing in UV-Visible characteristic band at 3315.90 (–NH2) which chamber. Most of the steps were optimized in confirms the attachment of urea and formation of order to achieve quantitative yields i.e. more 2-amino-4-(benzofuran-2-yl) oxazole Final than 70% yields. derivatives showed the expected bands for the The FT-IR in KBr (cm-1) spectra of compound 3, characteristic groups which are present in the indicated decrease in band strength of C=O compounds such as- C-N and –C-O-C bands. (1664) due to intermolecular hydrogen bonding Formation of new peaks at around 3000, 600- and specific band of C=C at 1588, C-O-C at 800 confirms the formation of derivatives.
CHO CH3 reflux for 10 hrs + CH3
OH Cl O unhydrous acetone O O salicylaldehyde chloroacetone 2-acetylbenzofuran
bromine in acetic acid
NH2 N CH2Br urea in ethanol O O O O 1-(1-benzofuran-2-yl)-2-bromoethanone 4-(1-benzofuran-2-yl)-1,3-oxazol-2-amine
aromatic aldehyde
Ar-CHO
O
O N N Ar
Fig. 1: Scheme for synthesis of 4-(1-Benzofuran-2-yl)-1,3-oxazole-2-Amine 34
IJRPC 2012, 2(1) Vidyashri et al ISSN: 22312781
Table 1: 4-(1-Benzofuran-2-yl)-1, 3-oxazole-2-Amine Derivatives Compound Aryl group Molecular formula Molecular weight % yield Melting point uncorrected o III a C18H12N202 288 60% 238 C
o III b C18H11N304 333 65% 250 C O2N
Table 2: Antibacterial Study of 4-(1-Benzofuran-2-yl)-1, 3-oxazole-2-Amine Derivatives S. no. compounds Zone of Inhibition in mm E-coli S. aureus 1 III a 20 17 2 III b 18 15 3 Amoxicillin 30 27 4 DMSO* 00 00 *DMSO:-Dimethyl sulfoxide
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