INTRODUCTION:

Widespread interest in the chemistry of chalcones, present in a large number of natural products has been due to their biological activities and their potential application as pharmacological agents. Chalcones are natural biocides and are well known intermediates for the synthesis of various organic heterocycles. The compounds with the backbone of chalcone have been reported to possess various biological and medicinal activities such as antimicrobial^1,4, anticancer², antioxidant³, antimalarial⁴, antifeedant⁴, antitumor^5,6, antimalarial^5,7, anti-inflammatory⁸, antitubercular^9,10 and anti-HIV¹¹ activities.

The chromones and related compounds are well known in the plant kingdom from algae to conifers. They possess a wide range of physiological activitieslike antibacterial^12,14, antifungal^13,14, antitumor¹⁵, anti-allergique¹⁶, anticancer¹⁷, anti-HIV¹⁸, anti-inflammatory¹⁹, antitubercular²⁰, antioxidant²¹ and antibiotic²² activities. In additions they are also works as optical polimer²³. The chromones are also interesting as structural scaffolds and have been found as privileged structure for drug development¹⁷. In our work, it was intended to synthesize some novel compounds containing chromone and chalcone moiety together.

RESULTS AND DISCUSSION:

1-(2’-aryl/furyl chromon-6’-yl)-3-aryl or heteroarylprop-2-en-1-ones [5(a-f)] have been synthesized from o-hydroxyacetophenone [1] in four steps. The first step, condensation¹⁸ of o-hydroxyacetophenone with furfural or benzaldehyde yielded 3-aryl or furyl-1-(2’-hydroxyphenyl)prop-2-en-1-one [2(a-b)] and the second step was the cyclization of 3-aryl or heteroaryl-1-(2’-hydroxyphenyl)prop-2-en-1-one [2(a-b)] to 2- aryl or furylchromones [3 (a-b)] by refluxing [2(a-b)] in DMSO and using iodine as catalyst. The structure assigned to [2 (a-b)] and [3 (a-b)] was confirmed on the basis of their IR and PMR spectral analysis. The third step was the Friedal-craft’s acylation of 2- aryl or furylchromone [3 (a-b)] to yield 6-acetyl-2-aryl or furylchromone [4 (a-b)]. These compounds, in their ir spectra exhibited two absorption bands at 1650-1664 (C=O str., COCH₃) and 1628-1594 cm^-1(C=O str., αβ-unsaturated ketone, chromone). The PMR spectra (recorded in CDCl₃), showed three protons singlet at δ2.68 of acetyl group and a disappearance of one proton signal of C-6 of chromone (at δ7.42). The fourth step was Claisen-Schemidt condensation of 6-acetyl-2- aryl or furylchromone [4 (a-b)] with different aldehydes to give 1-(2’-aryl/furyl chromon-6’-yl)-3-aryl or heteroarylprop-2-en-1-ones [5 (a-f)]. These compounds in their IR spectra, exhibited absorption bands at 3400-3300 cm^-1 (O-H str., H-bonded), 1665-1660 cm^-1(C=O str., αβ unsaturated ketone) and 1640-1635 cm^-1(C=O str., αβ unsaturated ketone, H-bonded), 1635-1630 cm^-1(C=O str., chromone) and PMR spectra (recorded in CDCl₃), showing a main feature of two protons of chalcone appearing in form of doublet at δ5.57 and δ6.72, and appearance of a doublet at δ8.85 to δ8.89 C₅-H of chromone ring.

Scheme 1

EXPERIMENTAL:

The reagent grade chemicals were purchased from commercial sources and purified by either distillation or recrystallization before use. Homogeneity of the compounds was checked on silica gel TLC plates of 2 mm thickness using n-hexane and ethyl acetate as solvent system. The visualization of spots was carried out in an iodine chamber. The physicochemical and spectroscopical data of synthesized compounds were in full agreement. All the melting points were determined in open glass capillary tubes and are uncorrected. The Infra-Red spectra were recorded in a Perkin-Elmer 1000 FT-IR spectrophotometer, using potassium bromide pellets; the frequencies are expressed in cm^-1. The proton magnetic resonance spectra were recorded on a Bruker-Avance II 400 NMR spectrophotometer (at 400 MHz) in CDCl₃ or DMSO-d₆ as specified; the chemical shifts (δ) are expressed in parts per million (ppm) downfield from Tetramethylsilane (TMS) as internal reference. The coupling constants (J) in PMR are reported in Hz.

General procedure for the preparation of 3-aryl or furyl-1-(2’-hydroxyphenyl) prop-2-en-1-one [2 (a-b)]:

A mixture of 2-hydroxyacetophenones (0.01 mol) and furfural or benzaldehyde (0.01 mol) was stirred in 30 ml ethanol and then 15 ml potassium hydroxide solution (40%) was added to it. The mixture was kept overnight at room temperature and then it was poured into crushed ice and neutralized with dilute hydrochloric acid. The product chalcone was separated out. Then it was filtered, washed and crystallized from ethanol.

General procedure for the preparation of 2-aryl/furyl chromones [3 (a-b)]:

0.01 mole of 3-aryl or furyl-1-(2-hydroxyphenyl)prop-2-en-1-one [2 (a-b)] was dissolved in 20 ml DMSO and few crystals of iodine were added. The solution was refluxed on oil-bath for 15 minutes and then pours into crushed ice, product chromone was separated out, then filtered, washed, dried and recrystallized with chloroform.

General procedure for the preparation of 6-acetyl-2-aryl/furylchromone [4 (a-b)]:

0.01 mole of 2-aryl/furyl chromones [3 (a-b)] and 0.015 mole of powdered anhydrous AlCl₃ were mixed together in 50 ml CS₂. Now 1 ml of CH₃COCl was added dropwise. The mixture was refluxed for an hour. CS₂ was distilled off and after work up solid product were separated, filtered, washed, dried and recrystallized.

6-acetyl-2-phenylchromone [4 (a)]:

A 2.2 gm (0.01 mol) of 2-phenylchromones [3 (a)] and 1.33 gm (0.015 mol) of powdered anhydrous AlCl₃ were mixed together in 50 ml CS₂, in a round bottom flask. Now 1 ml of CH₃COCl was added dropwise to the mixture. The mixture was refluxed for an hour. After the completion of reaction, CS₂ was distilled off and remaining solid was dropped into chilled water. Solid product were separated out, filtered, washed, dried and recrystallized with chloroform.

Chemical Formula: C₁₇H₁₂O₃; State (color): solid (light Yellow); Yield: 70%; m.p.: 162-164 °C; IR υ_max(KBr) cm^-1: 615, 840, 1575-1640 (CO, chromone), 1640-1680 (-COCH₃); ¹H-NMR (CDCl₃) δ 2.62 [s, 3H, -COCH₃], 6.75 [s, 1H, C₃-chromone], 7.35-7.58 [m, 4H, Ar-H], 7.82-7.84 [m, 2H, (C8-H chromone), (1H, Ar-H)], 8.37-8.39 [dd, 1H, C₇-H chromone], 8.67-8.68 [d, 1H, C₅-H chromone]

6-acetyl-2-furylchromone [4 (b)]:

Chemical Formula: C₁₅H₁₀O₄; State (color): solid (Yellow); Yield: 65%; m.p.: 146-148 °C; IR υ_max(KBr) cm^-1: 1210, 1640-1680 (COCH₃);¹H-NMR (CDCl₃) δ 2.68 [s, 3H, -COCH₃], 6.61-6.76 [m, 2H, (C₄-H, furan), (C₃-chromone)], 7.13-7.70 [m, 3H, (C₃-H and C₅-H furan), (C₈-H, chromone)], 8.40-8.43 [dd, 1H, C₇-H (chromone)], 8.85-8.86 [d, 1H, C₅-H (chromone)]

General procedure for the preparation of 1-(2’-aryl/furyl chromon-6’-yl)-3-aryl or heteroarylprop-2-en-1-ones [5 (a-f)]:

0.01 mol of 6-acetyl-2-aryl/furylchromone [4 (a-b)] was dissolved in 50 ml of EtOH and 0.01 mol of aldehyde was added to the solution. Now place the reaction mixture into crushed ice and 15 ml of KOH (40%) solution was poured dropwise. Reaction mixture was left overnight at room-temperature. Then reaction mixture was neutralized with dil. CH₃COOH and poured over crushed ice. Solid product separated out, filtered, washed, dried and recrystallized.

1-(2’phenylchromon-6’-yl)-3-phenylprop-2-en-1-one [5 (a)]:

2.64 gm (0.01 mol) of 6-acetyl-2-phenylchromone [4 (a)] was dissolved in 50 ml of EtOH and 0.01 mol (1.2 ml) of benzaldehyde was added to the solution. Now placed the reaction mixture into crushed ice and 15 ml of KOH (40%) solution was poured dropwise. Reaction mixture was left overnight at room-temperature. Then reaction mixture was neutralized with dil. CH₃COOH and poured over crushed ice. Solid product separated out, filtered, washed with water and ethanol, dried and recrystallized with CHCl₃.

Chemical Formula: C₂₄H₁₆O₃; State (color): solid (white); Yield: 70%; m.p.: 178-180 °C; IR υ_max(KBr) cm^-1: 820, 1180, 1260, 1575-1640 (CO str., chromone), 1660-1680 (CO str., αβ-unsaturated ketone);¹H-NMR (CDCl₃) δ 6.87 [s, 1H, (C₃-H chromone)], 7.43-7.49 [m, 4H, Ar-H], 7.53-7.70 [m, 6H, (2H, -CO-CH=CH-) and (4H, Ar-H)], 7.87-7.94 [m, 3H, (C₈-H chromone) and (2H, Ar-H)], 8.41-8.44 [dd, 1H, C₇-H chromone], 8.86-8.87 [d, 1H, C₅-H chromone].

3-furyl-1-(2’-phenylchromon-6’-yl)prop-2-en-1-one [5 (b)]:

Chemical Formula: C₂₂H₁₄O₄; State (color): solid (brownish yellow); Yield: 75%; m.p.: 170-172 °C; IR υ_max(KBr) cm^-1: 1140, 1575-1640 (CO str., chromone) ,1660-1680 (CO str., αβ-unsaturated ketone);¹H-NMR (CDCl₃) δ 6.54-7.17 [m, 3H, (C₃-H of chromone), (C₄-H furan ring) and (C₃-H furan ring], 7.46-7.50 [m, 3H, (2H, Ar-H) and (C₅-H furan ring)], 7.54-7.71 [m, 4H, (2H, -CO-CH=CH-) and (2H, Ar-H)], 7.89-7.93 [m, 2H, (C₈-H chromone) and (1H, Ar-H)], 8.39-8.42 [dd, 1H, C₇-H chromone], 8.86-8.87 [d, 1H, C₅-H chromone]

3-(p-chlorophenyl)-1-(2’-phenylchromon-6’-yl)prop-2-en-1-one [5 (c)]:

Chemical Formula: C₂₄H₁₅O₃Cl; State (color): solid (pinkish yellow); Yield: 70%; m.p.: 180-184 °C; IR υ_max(KBr) cm^-1: 860, 1180, 1660-1680 (CO str., αβ-unsaturated ketone), 1575-1670 (CO str., chromone);¹H-NMR (CDCl₃) δ 6.87 [s, 1H, (C₃-chromone)], 7.43-7.49 [m, 4H, phenyl],7.53-7.70 [m, 6H, (2H, -CO-CH=CH-) and (4H, Ar-H)], 7.87-7.94 [m, 2H, (C₈-H chromone) and (1H, Ar-H)], 8.41-8.44 [dd, 1H, C₇-H chromone], 8.86-8.87 [d, 1H, C₅-H chromone]

1-(2’-furylchromon-6’-yl)-3-phenylprop-2-en-1-one [5 (d)]:

Chemical Formula: C₂₂H₁₄O₄; State (color): solid (yellow); Yield68% m.p. 170-174 °C; IR υ_max(KBr) cm^-1: 1180, 1575-1640 (CO str., chromone) , 1660-1680 (CO str., αβ-unsaturated ketone);¹H-NMR (CDCl₃) δ 6.52-7.16 [m, 3H, (C₃H-chromone), (C₄-H furan ring) and (C₃-H furan ring], 7.45-7.48 [m, 3H, (2H, Ar-H) and (C₅-H furan ring)], 7.55-7.72 [m, 4H, (2H, -CO-CH=CH-) and (2H, Ar-H)], 7.87-7.90 [m, 2H, (C₈-H chromone) and (1H, Ar-H)], 8.37-8.40 [dd, 1H, C₇-H chromone], 8.85-8.86 [d, 1H, C₅-H chromone]

1-(2’-furylchromon-6’-yl)-3-furylprop-2-en-1-one [5 (e)]:

Chemical Formula: C₂₀H₁₂O₅; State (color): solid (brown); Yield: 75%; m.p.: 168-170 °C; IR υ_max(KBr) cm^-1: 820, 1180, 1575-1670 (CO str., chromone),1665-1680 (CO str., αβ-unsaturated ketone);¹H-NMR (CDCl₃): δ 6.50-6.58 (m, 1H, C_4’-H, furan ring B), δ 6.60-6.67 (m, 1H, C₄-H, furan ring A), 6.98-7.16 [m, 3H, (C_3’-H, furan ring B), (C₃-H, furan ring A), (C₃-H, chromone)], 7.50-7.70 [m, 5H, (C_5’-H, furan ring B), (C₅-H, furan ring A), (C₈-H, chromone) and 2H, -CH=CH-], 8.42-8.46 [dd, 1H, C₇-H (chromone)], 8.84-8.85 [d, 1H, C₅-H (chromone)]

3-(p-chlorophenyl)-1-(2’-furylchromon-6’-yl)-prop-2-en-1-one [5 (f)]:

Chemical Formula: C₂₂H₁₃O₄Cl; State (color): solid (yellow); Yield: 60%; m.p.: 176-178 °C; IR υ_max(KBr) cm^-1: 1180, 1575-1640 (CO str., chromone),1660-1680 (CO str., αβ-unsaturated ketone);¹H-NMR (CDCl₃): δ6.52-7.16 [m, 3H, (C₃H-chromone), (C₄-H furan ring) and (C₃-H furan ring], 7.45-7.90 [m, 8H, (2H, Ar-H), (C₅-H furan ring), (2H, -CO-CH=CH-), (2H, Ar-H) and (C₈-H chromone)], 8.37-8.40 [dd, 1H, C₇-H chromone], 8.85-8.86 [d, 1H, C₅-H chromone].

Antimicrobial screening:

The synthesized compounds were screened for their in vitro antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and antifungal activity against Aspergillus niger, Aspergillus flavus, by measuring the zone of inhibition in mm. The antimicrobial activity was performed by filter paper disc plate method at concentration 100 μg/mL and is reported in the graph. Muller Hinton agar and Sabouroud Dextrose agar were employed as culture medium and DMSO was used as solvent control for antimicrobial activity. Streptomycin and Fluconazole were used as standard for antibacterial and antifungal activities respectively.

Fig.1 Antibacterial and Antifungal activity

ACKNOWLEDGEMENTS:

The authors are thankful to CSIR, New Delhi for financial support during the research work to the Director, SAIF, Chandigarh for providing necessary spectral analysis and the Head, Department of Chemistry, J.V. College, Baraut, Baghpat (U.P.).

CONCLUSION:

The Friedel-Crafts acetylation of 2-aryl/heteroaryl chromones [3 (a-b)] using acetyl chloride and anhydrous Aluminiun chloride in Carbon disulphide yielded 6-acetyl chromones [4 (a-b)] in good yield has been found during investigation. It has been found that all the compounds showed moderate activity against the tested micro organisms.

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Received on 16.05.2014 Modified on 15.06.2014

Asian J. Research Chem. 7(7): July 2014; Page 649-652