Sulfuric Acid → methyl 2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)benzoate

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Reaction Conditions

Reaction Steps

Fluorescein (10 g; 30 mmol) was dispersed in methanol (30 mL) and concentrated sulfuric acid was added slowly. After the addition was complete the mixture was stirred with heating at 120° C. for 14 hours. After cooling the mixture, sodium bicarbonate was added to neutralize the mixture to give a solid. The crude product was filtered and washed with 2% sodium bicarbonate (200 mL), with water (4×) and with 1% acetic acid to give the fluorescein methyl ester (9.2 g, 26.4 mmol, 88.2% yield), m.p. 260-261° C. Step 8B. The fluorescein methyl ester (8 g, 23.1 mmol) and potassium carbonate (9.6 g, 69.3 mmol) were dissolved in dimethylformamide (50 mL) at 90° C. and to the solution was added toluenesulfonyl chloride (6.6 g, 34.7 mmol) slowly for 30 minutes. The mixture was then further stirred with heating at 110° C. for 5 hours. The mixture, after being cooled to room temperature, was poured into water (1L) to give a precipitate which was collected by filtration and washed with water to give the product(10 g, 20 mmol, 86.5% yield). Step 8c. The toluenesulfonyl fluorescein ester (2 g, 4 mmol) and indoline (1.4 g, 12 mmol) were dissolved in N-methylpyrollidinone (100 mL) and the solution was stirred with heating at 95° C. for 17 hours. After being cooled to room temperature the mixture was poured into water (600 mL) to form a precipitate. The precipitate was filtered, washed with water and dried to give the ester (1.7 g, 3.9 mmol, 96.8% yield). The desired dye was obtained by basic hydrolysis of the ester using the following method: the dye and aqueous sodium hydroxide (3 eq.) were dissolved in methanol and stirred with heating at 60° C. for 1 hour until TLC showed complete conversion. The crude product was purified by column chromatography (5% methanol in methylene chloride) to give the desired product. (1.35 g, 3.1 mmol, 78% yield) The structure was confirmed by NMR and mass spectroscopy.

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