Synthesis, Antimicrobial, Antioxidant Evaluation, and DFT Estimation of some New Cyclohexenone Derivatives Derived from Benzyloxy Chalcones

Abstract

Introduction: New cyclohexenone derivatives candidates were designed to discover their antioxidant and antibacterial activity potentials, respectively. background: In synthesis, the identification of novel and effective medications remains a primary focus. Due to some of the interactions between the medication and its receptors, the molecule links to particular targets, making its chemical structure crucial to its efficacy. Some structural alterations may grow, decrease, or even change in response to a change in activity. Benzyloxy benzaldehyde scaffold has an essentially planar confirmation with the two aromatic rings forming a dihedral angle [1]. O-alkylation was used to produce benzyloxy benzaldehyde, and the theory of density functional (DFT) computations were used to examine the characteristics of 4-benzyloxy benzaldehyde, a pharmaceutically significant molecule [2]. Some compounds possessing a benzyloxy benzaldehyde scaffold were shown to be the most effective and competitive inhibitors, and may be a viable scaffold for future drug development [3]. Chalcones are useful chemical synthesis intermediates generated by the combination of a ketone with an aldehyde throughout the involvement of an acid or alkaline catalyst [4]. Chalcones are flavonoids with an open chain and a reactive group called CO–CH=CH–, [5] that is capable of producing many heterocyclic compounds [6]. The relevance of chalcones and associated derivatives in pharmaceutical chemistry is astronomical [7]. Formulation of chalcone derivatives could indeed open up a new chemical space that could be used to find new drugs based on their bioactivities and their interrelations at the biomolecular level, where relevant [8]. Conjugated -π-systems in organic molecules, like those in naphthalene, are of immense importance as possible materials for utilization in relation to their nonlinear optical (NLO) properties [9]. 2-Acetyl Naphthalene Chalcones Exhibited Mild Antifungal and Antimicrobial Activity [10)] and (Naphthalen-2-yl) prop-2-en-1-one chalcones demonstrated a promising chemotherapeutic agent. [11]. One of the most significant carbon-carbon bonds-forming chemical reactions in organic synthesis, the Michael addition reaction which is a natural and rapid chemical process that finds widespread use in many different domains [12]. Numerous covalent medicines are considered to be anti-carcinogens and anti-inflammatory medications because they connect via Michael''s addition reaction [13]. Among the techniques for ring system formation found in a broad range of natural products, the inter- and intramolecular forms of the Michael addition reaction are extremely prevalent [14]. In Michael addition reactions involving carbon ion carrying a negative charge, the presence of basic catalysts allows chalcones to function as activated unsaturated systems [15], Chalcones and ethyl acetoacetate combined to form the derivatives of cyclohexenone, which had a modest antibacterial effect [16]. High yields and benign reaction conditions were produced by the conjugate addition of ethyl acetoacetate to chalcone derivatives having a thiophene ring in the presence of KOt-Bu in CH2CI2. The synthetic compounds have crucial functional groups in terms of a diverse range of chemical reactivity in organic synthesis [17]. The outcome of the Michael addition of ethyl acetoacetate was also analyzed in light of the catalysts'' organophilicity and accessibility [18]. Through the cyclo-condensation of aryl (2-thienyl) propenones and ethyl acetoacetate under the influence of NaOH, fused heterocyclic cyclohexenone compounds were created [15]. Cyclohexenone carboxylate derivatives were identified to exhibit anticancer activity [19]. On the other hand, some cyclohexenone derivatives were synthesized with the potential for application in photonic devices [20], whilst the presence of the pharmacologically active group linked to the cyclohexenone ring is responsible for the excellent antibacterial action of cyclohexenone [21]. Methods: Aldehydes with the diverse functional group were prepared from 4-hydroxy benzaldehyde and benzyl bromide and converted to chalcones by reaction with 4-substituted benzophenones and 2-acetyl naphthalene. When chalcone derivatives were subjected to ethyl acetoacetate, it produced new cyclohexenone derivatives through NaOH- catalyzed addition-ring closure reaction. The new compound structures were strengthened by their spectral information. The new compounds are examined for in vitro antifungal and antibacterial actions through broth microdilution technique, and they exhibited potential responses against various bacteria and fungi. Methods: Aldehydes with the diverse functional group were prepared from 4-hydroxy benzaldehyde and benzyl bromide and converted to chalcones by reaction with 4-substituted benzophenones and 2-acetyl naphthalene. When chalcone derivatives were subjected to ethyl acetoacetate, it produced new cyclohexenone derivatives through NaOH- catalyzed addition-ring closure reaction. The new compound structures were strengthened by their spectral information. The new compounds are examined for in vitro antifungal and antibacterial actions through broth microdilution technique, and they exhibited potential responses against various bacteria and fungi. Result: As a result, composites with (–F) group as a substituent on para position were established to be the forceful derivatives against S. aureus, E. coli organism, and C Albicans since this compound could inhibit the microbial and Fungai growth at lower concentrations compared to the standards (Ciprofloxacin HCl, and Fluconazole). Conclusion: DPPH radical scavenging experiments were used to evaluate proton donating antioxidant effects; it was exposed that compound 7c has the most significant antioxidant activity, while less than the standard ascorbic acid. Finally, HOMO-LUMO was calculated, which represents the quantum mechanical calculations of energies and conducted by the theory of density functional (DFT) method based on the level of (B3LYP) with 6-31G (d, p) basis set.

Access to Functionalized Cyclohex-2-enones from a Multicomponent Cascade Reaction of Readily Available Alkynes, Ketones, and Ethyl Acetoacetate

“…Cascade or tandem processes are one-pot multistep reactions that provide concise approaches to complex structures, and hence, they are powerful for synthetic transformations. − Cascade reactions are environmentally benign and economically efficient because they minimize waste, energy, labor, and time because the intermediates are not isolated and purified. − Recently, cyclohex-2-enone derivatives have attracted a considerable amount of attention − due to their potential applications in drug design and the medicinal industry. The biological activities of many compounds bearing a cyclohex-2-enone moiety have been well established, such as anti-inflammatory, antibacterial, − anticancer, and antimalarial activities.…”