Synthesis Characterization and Antimicrobial Activities of Schiff bases of 3-Formyl chromones
Ram Vishun Prasad1*, Ashutosh Singh2
1Assistant Professor, Department of Chemistry, Kisan PG College Babhnan, Gonda, India.
2Associate Professor, Department of Chemistry, KS Saket PG College Ayodhya, India.
*Corresponding Author E-mail: vishunram72@gmail.com
ABSTRACT:
Schiff bases are the compounds carrying imine or azomethine (–C=N–) functional group. These are the condensation products of primary amines with carbonyl compounds and were first reported by Hugo Schiff 12-13. Schiff bases form an important class of the most widely used organic compounds and have a wide variety of applications in many fields including analytical, biological, and inorganic chemistry.
Schiff bases have gained importance in medicinal and pharmaceutical fields due to a broad spectrum of biological activities like anti-inflammatory14-17, analgesic18, antimicrobial19-20, anticonvulsant21, antitubercular22, anticancer23-24, antioxidant25, anthelmintic26, and so forth. Apart from biological activities, Schiff bases are also used as catalysts, intermediates in organic synthesis, dyes, pigments, polymer stabilizers3, and corrosion inhibitors27.
Biological Significance:
Schiff base ligands have the ability to coordinate with metals by imine nitrogen and another group present in the molecule, usually associated with aldehyde or ketone. So many of the schiff bases and their complexes have been examined for their stimulating and significant properties, such as their catalytic activity in the hydrogenation of olefins, the ability to revert to oxygen, photochromic properties and the complexing capacity of some metals. Coordination of Schiff bases have demonstrated favorable applications for biological activity and modelling.
Schiff bases of Chromones:
There are many plausible mechanisms by which intake of vegetables and fruits may prevent carcinogenesis. Plant foods contain a wide verity of anticancer phytochemical with many potential bioactivities that may reduce cancer susceptibility28. Flavonoids and isoflavonoids are especially promising candidates for preventing cancer29. Flavonoids are plant secondary metabolites, present in all terrestrial vascular plants. Flavonoids are defined chemically as substances composed of a common phenyl chromone structure (C6-C3-C6) with one or more hydroxyl substituents. In recent years, considerable attention has been paid to understand the mechanism of their abilities to inhibit the cell cycle30, cell proliferation and oxidative stress and to detoxification enzymes, apoptosis, and the immune system. In view of heightened interest in the biological effects of flavonoids and isoflavonoids, the time is appropriate to review the current knowledge of the epidemiology, anti-carcinogenic activity, bioavailability and potential mechanisms of action of chromones. Building upon this foundation will facilitate development of new strategies and approaches for microbial control.
MATERIALS AND METHODS:
All experiments were conducted in open laboratory atmosphere. We purchased both solvents and reagents through commercial suppliers and even used them without any more purification. The different reagents used for the synthesis of Schiff bases of 3-formyl chromone were purchased from Merck and it was used as such. All solvents like ethanol, methanol, chloroform, petroleum ether, ethyl acetate and dichloromethane etc. were LR (Laboratory research) grade and used without distillation. Other general chemicals like urea, sodium hydroxide, sulfuric acid, HCl, silica gel, iodine etc. were of LR grade. In all experimental procedure double-distilled water was used. The completion of reaction is determined on TLC. The compounds' melting points were recorded in open capillaries and is uncorrected. Elemental analysis (C H and N) was performed on a Perkin-Elmer 2400 CHN elemental analyzer. The FT-IR spectra were recorded on a FT-IR Bruker spectrophotometer with KBr disks from KBr pellets in the range from 4000 to 400 cm-1. 1H NMR spectra were recorded on a 400-MHz Bruker Avance spectrometer with TMS as internal standard.
Synthesis of Schiff bases of Chromones (present work):
We are interested to synthesize a series of 3-formylchromone condensed Schiff bases using facile and well-established methodologies to get better anti-microbial agents are shown in the scheme 1. In this way we designed, synthesized and characterized a series of novel schiff base ligands (L1-L4). Structure elucidation and characterization of Schiff base ligands (L1-L4) have been reported. A synthetic route for the series of schiff bases of 3-formyl chromones (L1-L4) were outlined in scheme 1.
The initial step, an equimolar quantity of 1-amino-2-propanol or 2-amino-1-phenylethanol and 3-formyl chromones were condensed in methanol or ethanol for 8-14 hours. During the condensation, the reaction mixture turned into reddish-brown. After completing the reaction (observed by the TLC), the reaction mixture left to cool, then filter the solid, washed with water followed by suitable solvents and recrystallized.
SCHEME - 1
|
S N |
COMPOUND |
|
R1 |
R2 |
R3 |
|
01 |
Ligand-1 |
L1 |
H |
H |
CH3 |
|
02 |
Ligand-2 |
L2 |
CH3 |
H |
CH3 |
|
03 |
Ligand-3 |
L3 |
Cl |
H |
CH3 |
|
04 |
Ligand-4 |
L4 |
Br |
H |
CH3 |
|
05 |
Ligand-5 |
L5 |
H |
H |
Ph |
|
06 |
Ligand-6 |
L6 |
CH3 |
H |
Ph |
|
07 |
Ligand-7 |
L7 |
Cl |
H |
Ph |
|
08 |
Ligand-8 |
L8 |
Br |
H |
Ph |
Experimental:
In this section we will discuss the experimental conditions and spectroscopical data of synthesised compounds.
Synthesis of Ligands (L1-L4):
a).3-(N-(propan-2-ol)methyl)-4H-chromen-4-one [L1]:
A solution of 3-formyl chromone (1.74 g, 0.01 mol) and 1-amino-2-propanol (0.75 g, 0.01 mol) in 20 ml methanol is condensed for 8 h. Reaction was monitored by TLC, after completion of reaction, reaction mixture turns into yellowish color. Then the reaction mixture was poured on crushed ice, filtered, washed with distilled water followed by ethanol, dried under vacuum and then yellow colored solid was obtained. The product was recrystallized from ethanol.
A light-yellow solid, yield: 75%, mp: 198-202 °C, 1H-NMR (CDCl3, 400 MHz) :1.12-1.24 (3H, d, J = 6.2 Hz, CH3), 3.70-3.87 (3H, m, CH2 and CH), 4.98-5.02 (1H, OH), 7.14-7.48 (3H, m, (C5-H, C6-H and C8-H chromone)), 7.62-7.88 (2H, m, (C7-H and Ar-CH=N)), 8.13 (1H, s, (C2-H chromone)); IR υmax (KBr) cm-1: 1186 (C-O str., side chain), 1436 (C=N str.), 1640 (C=O str., chromone); Analytical Calculations (%) for C13H13O3N: C- 67.53, H- 5.63, N- 6.06; Found: C- 68.63, H-5.84, N- 6.10.
b).3-(N-(propan-2-ol)methyl)-4H-6-methyl-chromen-4-one [L2]:
A solution of 3-formyl-6-methyl chromone (1.88 g, 0.01 mol) and 1-amino-2-propanol (0.75 g, 0.01 mol) in 25 ml methanol is condensed for 12 hrs. Reaction was monitored by TLC, after completion of reaction, reaction mixture turns into yellowish color. Then the reaction mixture was poured on crushed ice, filtered, washed with distilled water followed by ethanol, dried under vacuum and then yellow colored solid was obtained. The product was recrystallized from ethanol.
A yellow solid, yield: 70%, mp: 202-204 °C, 1H-NMR (CDCl3, 400 MHz) :1.12-1.24 (3H, d, J = 6.2 Hz, CH3), 2.28-2.42 (3H, m, CH3-Chromone), 3.70-3.87 (3H, m, CH2 and CH), 4.98-5.02 (1H, OH), 7.18-7.46 (2H, m, (C5-Hand C8-H chromone)), 7.62-7.88 (2H, m, (C7-H and Ar-CH=N)), 8.13 (1H, s, (C2-H chromone)); IR υmax (KBr) cm-1: 1186 (C-O str., side chain), 1436 (C=N str.), 1640 (C=O str., chromone); Analytical Calculations (%) for C14H15O3N: C- 68.57, H- 6.12, N- 5.71; Found: C- 68.72, H-6.64, N- 5.70.
c).3-(N-(propan-2-ol)methyl)-4H-6-chloro-chromen-4-one [L3]:
A solution of 3-formyl-6-chloro-chromone (2.10 g, 0.01 mol) and 1-amino-2-propanol (0.75 g, 0.01 mol) in 20 ml methanol is condensed for 6-8 hrs. Reaction was monitored by TLC, after completion of reaction, reaction mixture turns into reddish color. Then the reaction mixture was poured on crushed ice, filtered, washed with distilled water followed by ethanol, dried under vacuum and then yellow colored solid was obtained. The product was recrystallized from ethanol.
A red Colour solid, yield: 70%, mp: 210-214 °C, 1H-NMR (CDCl3, 400 MHz) :1.12-1.24 (3H, d, J = 6.2 Hz, CH3), 3.70-3.87 (3H, m, CH2 and CH), 4.98-5.02 (1H, OH), 7.13-8.16 (5H, m, (Ar-CH=N, C2-H, C5-H, C7-H and C8-H chromone)); IR υmax (KBr) cm-1: 1186 (C-O str., side chain), 1436 (C=N str.), 1640 (C=O str., chromone); Analytical Calculations (%) for C13H12O3NCl: C- 58.65, H- 4.51, N- 5.26; Found: C- 58.72, H-4.62, N- 5.41.
d).3-(N-(2-phenylethanol)methyl)-4H-chromen-4-one [L4]:
A solution of 3-formyl chromone (1.74 g, 0.01 mol) and 2-Amino-1-phenylethanol (1.38 g, 0.01 mol) in 10 ml methanol and 15 ml ethanol is condensed for 14 h. Reaction was monitored by TLC, after completion of reaction, reaction mixture turns into yellowish color. Then the reaction mixture was poured on crushed ice, filtered, washed with distilled water followed by ethanol, dried under vacuum and then yellow colored solid was obtained. The product was recrystallized from methanol.
A yellow solid, yield: 65%, mp: 210-212 °C, 1H-NMR (CDCl3, 400 MHz) : 3.68-4.12 (2H, m, CH2), 4.86-5.06 (2H, OH and CH), 7.14-7.48 (8H, m, (Ar-H, C5-H, C6-H and C8-H chromone)), 7.62-7.92 (2H, m, (C7-H and Ar-CH=N)), 8.13 (1H, s, (C2-H chromone)); IR υmax (KBr) cm-1: 1186 (C-O str., side chain), 1446 (C=N str.), 1640 (C=O str., chromone); Analytical Calculations (%) for C18H15O3N: C- 73.72, H- 5.12, N- 4.78; Found: C- 74.04, H-5.24, N- 4.92.
e).3-(N-(2-phenylethanol)methyl)-4H-6-methyl-chromen-4-one [L5]:
A solution of 3-formyl-6-methyl chromone (1.88 g, 0.01 mol) and 2-Amino-1-phenylethanol (1.38 g, 0.01 mol) in 10 ml methanol and 15 ml ethanol is condensed for 14 h. Reaction was monitored by TLC, after completion of reaction, reaction mixture turns into pinkish color. Then the reaction mixture was poured on crushed ice, filtered, washed with distilled water followed by ethanol, dried under vacuum and then yellow colored solid was obtained. The product was recrystallized from methanol.
A pink colour solid, yield: 72%, mp: 222-224 °C, 1H-NMR (CDCl3, 400 MHz) : 1.98-2.44 (3H, CH3),3.68-4.12 (2H, m, CH2), 4.86-5.06 (2H, OH and CH), 7.22-7.48 (7H, m, (Ar-H, C5-H, and C8-H chromone)), 7.62-7.92 (2H, m, (C7-H and Ar-CH=N)), 8.13 (1H, s, (C2-H chromone)); IR υmax (KBr) cm-1: 1186 (C-O str., side chain), 1436 (C=N str.), 1640 (C=O str., chromone); Analytical Calculations (%) for C19H17O3N: C- 74.27, H- 5.54, N- 4.56; Found: C- 74.36, H-5.58, N- 4.64.
f).3-(N-(2-phenylethanol)methyl)-4H-6-chloro-chromen-4-one [L6]:
A solution of 3-formyl-6-chloro-chromone (2.10 g, 0.01 mol) and 12-Amino-1-phenylethanol (1.38 g, 0.01 mol) in 10 ml methanol and 15 ml ethanol is condensed for 14 h. Reaction was monitored by TLC, after completion of reaction, reaction mixture turns into pinkish color. Then the reaction mixture was poured on crushed ice, filtered, washed with distilled water followed by ethanol, dried under vacuum and then yellow colored solid was obtained. The product was recrystallized from ethanol.
A yellow solid, yield: 65%, mp: 210-212°C, 1H-NMR (CDCl3, 400 MHz) : 3.90-4.12 (2H, m, CH2), 4.87-5.08 (2H, OH and CH), 7.21-7.52 (8H, m, (Ar-H, C5-H, C6-H and C8-H chromone)), 7.60-7.94 (2H, m, (C7-H and Ar-CH=N)), 8.13 (1H, s, (C2-H chromone)); IR υmax (KBr) cm-1: 1186 (C-O str., side chain), 1436 (C=N str.), 1646 (C=O str., chromone); Analytical Calculations (%) for C18H14O3NCl: C- 65.85, H- 4.27, N- 4.27; Found: C- 66.63, H-4.84, N- 4.26.
Antibacterial and Antifungal Activity:
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 reported in Table 7.1. Muller Hinton agar & 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.
CONCLUSION:
In summary, present work demonstrate an efficient method for the synthesis of novel schiff bases of chromones L1 – L6 under reflux conditions. The newly synthesized compounds have been characterized on the bases of elemental analysis, PMR and IR spectra. These compounds have been evaluated for their antibacterial and antifungal activity. It has been found that all of them show moderate activity against the tested microorganisms.
ACKNOWLEDGEMENTS:
The authors are thankful to the Head, Department of Chemistry, K.S. Saket P.G College Ayodhya, Faizabad for valuable support and laboratory facilities. The authors are also thankful to the Director, SAIF, CDRI, Lucknow for spectral analysis of compounds.
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Received on 07.02.2022 Modified on 02.03.2022
Accepted on 20.03.2022 ©AJRC All right reserved
Asian J. Research Chem. 2022; 15(3):235-239.
DOI: 10.52711/0974-4150.2022.00042