Synthesis of 18F-labeled phenolphthalein and naphtholphthalein

• We performed a direct fluorination of phenolphthalein and naphtholphthalein.
• The reaction leads to specific fluorination into ortho positions to OH groups.
• All the fluorinated derivatives act like pH indicators.
• The products were also labeled with 18F to be used for in vivo pH detection.
• Difluoronaphtholphthalein has an optimal pKa 7.24 and absorption at 665 nm.

The fluorination of phenolphthalein and naphtholphthalein was performed with diluted fluorine gas under acidic conditions. For both compounds we observed an electrophilic fluorination into ortho position to the hydroxyl group. Through the use of this reaction we synthesized and characterized mono- and difluorinated derivatives of phenolphthalein and naphtholphthalein. The compounds were also prepared in the 18F labeled form, which are usable as a new type of probe for in vivo pH measurement in biological objects using Cerenkov imaging or combination of light absorption and PET.

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