Studies in the xanthone series. Part XII. A general synthesis of polyoxygenated xanthones from benzophenone precursors

Abstract

2.3,4.5-tetra-, and 1.3.5.6.7-penta-oxygenated xanthones have been synthesised by preparation of 2-hydroxy-2'methoxybenzophenones under Friedel-Crafts conditions, and subsequent base catalysed cyclisation to eliminate methanol. Acid or base catalysed selective demethylations of polymethoxyxanthones, and of benzophenones lead to efficient synthesis of natural hydroxymethoxyxanthones, and of hydroxymethoxybenzophenones. Selective methylation procedures are also given.XANY natural xanthones are not readily accessible by existing methods and an alternative approach was required. Synthetic considerations largely concern orientation control and selective methylation and demethylation. The synthesis of Grover et al.* from salicyclic acid and phenol derivatives does not always give the required xanthonesJ5 and the reaction may be accompanied by unwanted demethylations.6 The procedure may also lead to benzophenone formation 7 or a multiplicity of products.s The alternative now described is an efficient general synthesis, and involves formation of 2-hydroxy-2'-methoxybenzophenones, followed by the quantitative elimination of methanol in the presence of alkali to give xanthones.1° A similar base catalysed elimination (of water) was noted by Nishikawa and Robinson l1 in 1922, in the synthesis of lJ3-dihydroxyxant hone.Similar routes 12, l3 to highly oxygenated xanthones have been demonstrated recently, but these involve slow acylations l4 of polyhydric phenol derivatives with benzoic acids in trifluoroacetic anhydride. The present report includes syntheses of benzophenones and monoto pent a-oxygenat ed xanthones.Orientation and Demethylatio9t i.p2 Benxophenone Synthesis.-The synthesis of benzophenones suitable as precursors for cyclisation to xanthones is conveniently achieved at room temperature by the Friedel-Crafts acylation of methoxybenzene derivatives with the appropriately substituted benzoyl chloride in the presence of aluminium chloride in ether. That preferential para-acylation occurs under these conditions is shown by the reaction of benzoyl chloride and veratrole which gives 3,4-dimethoxybenzophenone. In cases 1

1H and13C NMR Spectroscopy of mono-, di-, tri- and tetrasubstituted xanthones

“…7 The 1D and 2D NMR spectroscopic techniques applied in this study allow an unambiguous assignment for all the proton and carbon resonances. The xanthonic compounds examined in this study included natural (1,3,7,10,20) and synthetic derivatives (2, 4È6, 8, 9, 11È19, 21È24) (Fig. 2).…”

Synthesis of Heterocyclic Compounds via Nucleophilic Aroylation Catalyzed by Imidazolidenyl Carbene

“…30) The first one is based on the cyclization of 2-hydroxybenzophenones, [31][32][33] and the second involves the cyclodehydration of o-phenoxybenzoic acids. [34][35][36] Our method is based on the cyclization of 2,2Ј-difluorobenzophenones 5 prepared by NHC-catalyzed aroylation of 3,4-difluoronitrobenzene (3) and fluorobenzaldehydes 4 (Chart 2).…”

An efficient and convenient microwave-assisted chemical synthesis of (thio)xanthones with additional in vitro and in silico characterization

“…35 Synthetically, xanthones are usually obtained by chemical synthesis from benzophenones or diaryl ethers under harsh reaction conditions and/or in the presence of strong acids or toxic metals. 36 In the literature, different methods have been reported [37][38][39][40][41][42] so far for the synthesis of xanthones, with varying yields. Base catalyzed cyclisation of a substituted benzophenone precursor to obtain some polymethoxyxanthones has also been reported, but the yields were low.…”