517. β-Aroylpropionic acids. Part XVI. The conversion of γ-oxo-γ-2-xanthenylbutyric acid into 2,3-benzoxanthone

Abstract

I -0x0y -2 -xanthen y 1 but yric Acid into 2,3 -Benxoxanthone .By A. M. EL-ABBADY, S. AYOUB, and F. G. BADDAR.y-Oxo-y-2-xanthenylbutyric acid has been reduced to y-Z-xanthenylbutyric acid and then cyclised to 1',2',3',4'-tetrahydro-4'-0~0-2,3-benzoxanthen. This is reduced to 1',2',3',4'-tetrahydro-2,3-benzoxanthen, then dehydrogenated, and oxidised to 2,3-benzoxanthone. y-2-Xanthenylbutyric ester has been condensed with diethyl oxalate, and the oxalyl derivative cyclised to 1',2'-dihydro-Z,3-benzoxanthen-3',4'-dicarboxylic anhydride. This on dehydrogenation, decarboxylation, and oxidation gives 2,3-benzoxanthone.CONTRARY to a report by Burtner and Brown1 the Friedel-Crafts reaction of xanthen with succinic anhydride in benzene gave a mixture of y-oxo-y-2-xanthenylbutyric acid (I) and p-benzoylpropionic acid. However, condensation in acetylene tetrachloride afforded the keto-acid (I) in 96% yield. The structure of this keto-acid was established by its oxidation to xanthone-2-carboxylic acid (XIII) . Mild oxidation of either y-oxo-y-2xanthenylbutyric acid (I) or its methyl ester by potassium permanganate in aqueous acetone yielded y-oxo-y-2-xanthonylbutyric acid (11; R = H) or its methyl ester respectively. Hydrolysis of the diketo-ester (11; R = Me) with 5% alcoholic potassium hydroxide gave the diketo-acid (11; R = H), but treatment with 10% aqueous sodium hydroxide led to a phenolic acid. This was probably due to the rupture of the heterocyclic ring, to give ~-(4-hydroxy-3-o-hydroxybenzoylbenzoyl)propionic acid (111). Its structure was based on the fact that it cyclised back to the original ester (11; R = Me) on attempted methylation with methyl sulphate and potassium carbonate in acetone. A similar result was obtained with 2,Z'-dihydroxybenzophenone, which was converted into xanthone on attempted methylation with alkaline methyl sulphate 3a or on evaporation of its alkaline solution.36The structure of the acid (111) was further supported by its infrared spectrum. It showed a broad band a t 3200-3125 and a weak sharp band a t 3545 cm.-l (in CHClJ, characteristic for the chelated and the free OH group, respective1y.b Two bands a t 1695 and 1639 cm.-l (in Nujol) are characteristic for the side chain and the o-hydroxycarbonyl group, respectively.& Reduction of y-oxoy-2-xanthenylbutyric acid (I) by Clemmensen's method, or less satisfactorily by the Wolff-Kishner method, gave y-2-xanthenylbutyric acid (IV; R = H).Conversion of the acid (V; R = H) into 2,3-benzoxanthone (XIV) was carried out by two routes: ( A ) The acid chloride of (IV; R = H) was best cyclised with anhydrous stannic chloride, affording a cyclic ketone, theoretically of structure (VII) or (XV). It was proved

Synthesis and antiallergic activity of some mono- and disubstituted xanthone-2-carboxylic acids

“…Anal. (C16H1206S) C, H, S. 5-Hydroxy-7-(methylthio)xanthone-2-carboxylic Acid (16). HI (116 mL, 47%) was added dropwise to 380 mL of ice-cooled Ac20 with vigorous stirring.…”

“…HI (116 mL, 47%) was added dropwise to 380 mL of ice-cooled Ac20 with vigorous stirring. After adding 17.0 g (53.8 mmol) of 15g, the resulting suspension was refluxed for 20 h. The hot reaction mixture was diluted with 400 mL of H20 and cooled and the product (16) isolated by suction filtration: 14.3 g (88%); mp 364-366 °C dec. Anal. (C15H10O6S) C, H, S.…”

Carboxyxanthones: Bioactive Agents and Molecular Scaffold for Synthesis of Analogues and Derivatives

“…The synthesis of 9-oxo-9 H -xanthene-2-carboxylic acid ( 162 ) was first reported by Anschutz et al [151], in 1925, from 2-methylphenylsalicilate. Later, in 1960, El Abbady et al [152], described its synthesis through oxidation of γ-oxo-γ-2-xanthenylbutyric acid. In 1977, Graham and Lewis [153], described other synthetic strategy, via benzophenone intermediate, through reaction of 2-methoxybenzoic acid with methyl 4-hydroxybenzoate.…”

“…El Abbady [152] reported, in 1960, the synthesis of carboxyxanthone derivative 288 (Table 2) through oxidation of 4-oxo-4-(9 H -xanthen-2-yl)butanoic acid with potassium permanganate in acetone. In 1990, Sato et al [174] reported the synthesis of several new carboxyxanthone derivatives ( 289 – 320 ).…”

Synthesis of a Benzo[5,6]cyclohepta[1,2-b]thiophene and Thieno[3,2-c]benzazepine Derivatives

“…The resulting isocyanate 14 was used in the next reaction without purification to give the lactam 15. Furthermore, synthesis of the key intermediate 16 was accomplished by oxidation 13 of 15 with potassium permanganate in acetone in 88% yield.…”