Novel ZrOCl2·8H2O-Catalysed One-Pot Multicomponent Synthesis of 9,10-Dihydro-8H-benzo[a]xanthen-11(12H)-one Derivatives

A simple and efficient protocol for the synthesis of highly substituted xanthenes is developed through the condensation of β-naphthol, aldehydes, and cyclic 5,5-dimethylcyclohexane-1,3-dione with zirconium oxychloride octahydrate as a catalyst via multicomponent condensation strategy. The present method gives good to excellent yields of substituted 9,10-dihydro-8H-benzo[a]xanthen-11(12H)-one derivatives. 1. Introduction Xanthenes and benzoxanthenes are biologically important drug intermediates. They are cited as active oxygen hetero-cycles possessing antibacterial. Research on xanthenes, especially benzoxanthenes, has emerged in organic synthesis due to their wide range of biological and therapeutic properties like antiviral [1], antibacterial [2], and anti-inflammatory activities [3], as well as in photodynamic therapy [4] and as antagonists of the paralyzing action of zoxazolamine [5]. Xanthenes are also available from natural sources. Popularly known, Santalin pigments have been isolated from a number of plant species [6]. Furthermore, due to their useful spectroscopic properties, they are used as dyes [7], in laser technologies [8], and in fluorescent materials for visualization of biomolecules [9]. Many procedures are disclosed to synthesize xanthenes and benzoxanthenes like cyclodehydrations [10], trapping of benzynes by phenols [11], alkylations of hetero atoms [12], and cyclocondensations between 2-hydroxy aromatic aldehydes and 2-tetralone [13]. Benzaldehydes and acetophenones bearing tethered carbonyl chains underwent the intermolecular phenyl-carbonyl coupling reactions in the presence of samarium diiodide and hexamethylphosphoramide to afford xanthenes [14]. In addition, 14H-dibenzo[a,j]xanthenes and related products are prepared by reaction of β-naphthol with form amide [15], 1-hydroxy methyl-naphthalen-2-ol [16], and carbon monoxide [17]. Initially, we investigated the condensation reaction of β-naphthol, benzaldehyde, and 5,5-dimethylcyclohexane-1,3-dione using different Lewis acids catalysts and conditions such as La(OTf)3, ZnCl2, AlCl3, and Sr(OTf)3 [18]. However, many of these reagents or catalysts are expensive, harmful, and difficult to handle especially on a large scale. 2. Experimental 2.1. Materials and Instruments All reagents were purchased from Merck. Aldehydes were distilled before use. Melting points were determined using a Linkman HF591 heating stage, used in conjunction with a TC92 controller, and re-uncorrected. NMR spectra were recorded using either a Brucker DRX500 machine at room temperature. 1H, 13C NMR, and 19F NMR