Calcinized Eggshell: An Environmentally Benign Green Catalyst For Synthesis Of Newer Acetamide Derivatives And Its Antimicrobial Activity

The growing issue of antimicrobial resistance (AMR) has made the development of novel antimicrobial drugs a top goal in modern medicine. This talk explores the methods, obstacles, and developments in the creation of new antimicrobial medications, highlighting the necessity of a multimodal strategy that incorporates cutting-edge research methods and interdisciplinary cooperation. Solvents, which are required for the synthesis of new drugs and are either toxic or flammable, significantly increase the overall cost of synthesis. Green chemistry (catalyst) often improves selectivity, speeds up reactions, and makes product separation and purification simpler than traditional methods. Among the few parts of green science, the decrease or substitution of unstable natural solvents from the response medium is of most extreme significance. Chemists must now look for as many environmentally friendly methods as possible due to the growing economic and environmental concerns in recent years. In ongoing work we utilize the green methodology by utilizing less risky impetus calcinated egg shell (CES) for the combination of new acetamide derivates [1]. Antibiotics have saved countless lives through research and commercialization, making them one of the most commonly prescribed antibiotics today. Several bacterial diseases, including diarrhea, food poisoning, and rheumatic fever, are brought on by multidrug-resistant bacteria. Resistance to antibiotics that are currently available is rapidly rising, posing a serious threat to human health2. One of the most active classes of chemicals, coumarin and its derivatives has a wide range of biological effects. Antibacterial, antifungal, calming, anticoagulant, against HIV, and anticancer properties have been exhibited for a few of these substances.Various subbed coumarin analogs have antibacterial, anticonvulsant, acetyl cholinesterase inhibitory, and aldehyde correct inhibitory properties.[3, 4, 5] A crucial area of research for the growing interest in thiazole chemistry is the design of novel compounds and the wide variety of pharmaceutical and medical applications for which they can be used. Many natural bioactive substances, like marine alkaloids, have the thiazole ring as a fundamental structural component. The thiazole ring (antineoplastic drug) is present in penicillin (wide-spectrum antibiotic), sulfathiazole (antimicrobial drug), ritonavir (antiretroviral drug), abafungin (antifungal drug), and tiazofurin (antifungal drug).[6, 7, 9, 10]

MATERIAL AND METHODS

Merck, Germany, and Loba Organization provided all synthetic substances and solvents. 1HNMR spectra were obtained using Bruker Advance 500 MHZ equipment. Utilizing thin-layer chromatography (TLC), the purity of the was determined. Using an electronic Veego (model:-VMP-D), the melting points were determined in an open capillary. The synthesized compounds' IR spectra were obtained using the Shimadzu 8400 FT-IR Spectrophotometer.

Synthesis of 3-acetyl-2H-chromen-2-one

The solution was made up of 25.65mL (0.1mol) ethyl acetoacetate and 21.29mL (0.1mol) salicylaldehyde. In an ice bath, it was chilled. Rapid stirring was used to add 2ml (0.02mol) of piperidine to the liquid. The reaction mixture was held at a low temperature. The yellowish material was separated after 20 minutes, filtered, and washed with ethanol thereafter. It was recrystallized from ethanol from ethanol: water (7:3)[10]. Yield-85%, Melting point-110-1140c, IR Spectra (KBr) - C=O (?, ? unsaturated) at 1600 to 1700 cm-1 in addition to ketone C=O at 1745 to 1715 cm-1, aliphatic C-H 3000 to 2850 cm-1, aromatic C-H 3150 to 3000 cm-1.

Synthesis of 2-oxo-2H-chromene-3-carbonyl bromide

4.7gm (0.025mol) 3-acetycoumarin was taken in a beaker and dissolved in 20 ml of chloroform. 4gm (0.05mol) bromine was taken in round bottom flask. 13 ml of chloroform was added to it. The two mixtures were mixed by slowly stirring and refluxed for 1hr. After 1hr reaction mixture was cooled, filtered and washed with petroleum ether. It was recrystallized from ethanol: chloroform (2:1)[5]. Yield-78%, Melting point-140-1440c, IR Spectra- C-Br at 756 cm-1, lactone at 1700 to 1600 cm-1,  ketone C=O at 1745 to 1715 cm-1, aromatic C=C at 2350 to 2100 cm-1, aromatic C-H 3150 to 3000 cm-1.

Synthesis of 3-(5-amino-1, 3-thiazol-2-yl)-2H-chromen-2-one

1gm of 3-bromo acetylcoumarin (1mol) and 1gm (1mol) of thiourea were taken in 250 ml of round bottom flask and dissolved in 20 ml of ethanol by slowly stirring for 15min. After 15 min 0.5ml of ammonia was added to it. The reaction mixture was heated under the reflux for 30min. After 30min the reaction mixture was poured in ice cold water (50ml), filtered and dried. It was recrystallized from ethanol [11].   Yield-85%, Melting point-220-2220c, IR Spectra(KBr) - C-S at 635 to 500 cm-1, aromatic C=N at 1660 to 1340 cm-1 ,lactone at 1700 to 1600 cm-1,  amine N-H at 3500 to 3100 -1cm.

Synthesis of 2-chloro-N-[2-(2-oxo-2H-chromen-3yl)-1, 3-thizol-5-] acetamide

In round bottom flask, 0.7gm (0.005mole)of  3-(5-amino-1, 3-thiazol-2-yl)-2H-chromen-2-one, 0.5gm of  anhydrous potassium carbonate and 1ml of triethyl amine  were taken and dissolved into 65ml of dry chloroform with slowly stirring. The reaction mixture was refluxed for 4-5hr. After 5hr the reaction mixture was evaporated. The resulting solid was washed with cold water and dried.  It was recrystallized from ethanol: water (80:20)[12].  Yield-85%%, Melting point-230-2320c, IR Spectra (KBr) 591 (C-S), 643 (C-Cl), 1249 (C-O), 1319 (C-N), 1556(C=N), 1651(C=O), 1735(keto C=O), 1797(amide N-H), 2327(Ar C=C), 3078(C-H), 3140(Ar C-H), 3371(amine N-H)

Synthesis of 1-(substituted phenyl)-3-[4-(2-oxo-2H-chromen-3-yl)-1,3-thiazol-2-yl]acetamide

3gm (0.13mol) of 2-chloro-N-[2-(2-oxo-2H-chromen-3yl)-1, 3-thizol-5-] acetamide and substituted aniline were taken into the mortar. And calcinated egg shell to it which was first calcinated by heating in muffle furnace at very high temperature. This reaction mixture was mix continues with pestle at room temperature for 2hr. After 2 hr the reaction mixture was kept for the TLC solid was separated, which was filtered and dried. It was recrystallized by using ethanol: water (80:20) [3].

RESULTS

Antimicrobial screening of the synthesized compounds for zone of inhibition and Minimum Inhibitory Concentration was performed using the Cup plate method. The Antibacterial action was tried against different gram positive and Gram-negative microorganisms and hostile to parasitic action against different contagious strains contrasted and standard medication.