title: Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate.
abstract: An electrochemical method with the ability to conduct (18)F-fluorination of aromatic molecules through direct nucleophilic fluorination of cationic intermediates is presented in this paper. The reaction was performed on a remote-controlled automatic platform. Nucleophilic electrochemical fluorination of tert-butyloxycarbonyl (Boc) protected catechol, an intermediate model molecule for the positron emission tomography (PET) probe (3,4-dihydroxy-6-[(18)F]fluoro-L-phenylalanine), was performed. Fluorination was achieved under potentiostatic anodic oxidation in acetonitrile containing Et3N·3HF and other supporting electrolytes. Radiofluorination efficiency was influenced by a number of variables, including the concentration of the precursor, concentration of Et3N·3HF, type of supporting electrolyte, temperature and time, as well as applied potentials. Radio-fluorination efficiency of 10.4±0.6% (n=4) and specific activity of up to 43GBq/mmol was obtained after 1h electrolysis of 0.1M of 4-tert-butyl-diboc-catechol in the acetonitrile solution of Et3N·3HF (0.033M) and NBu4PF6 (0.05M). Density functional theory (DFT) was employed to explain the tert-butyl functional group facilitation of electrochemical oxidation and subsequent fluorination.
authors.affiliation: Department of Molecular & Medical Pharmacology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: He
authors.affiliation: Division of Theoretical Chemistry & Biology, School of Biotechnology, KTH Royal Institute of Technology, 106 91 Stockholm, Sweden.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Molecular & Medical Pharmacology, University of California, Los Angeles, CA 90095, United States.
authors.forename: Ines
authors.initials: I
authors.lastname: Alfeazi
authors.affiliation: Department of Molecular & Medical Pharmacology, University of California, Los Angeles, CA 90095, United States. Electronic address: samsadeghi@mednet.ucla.edu.
authors.forename: Saman
authors.initials: S
authors.lastname: Sadeghi
mesh_terms: D017554:Carbon Compounds, Inorganic / Q000138:chemical synthesis*; D004563:Electrochemistry / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000032:analysis / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D019275:Radiopharmaceuticals / Q000032:analysis / Q000138:chemical synthesis*
chemical_list: D017554:Carbon Compounds, Inorganic; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals
keywords: Aromatic substitution; DFT simulation; Electrochemical radiosynthesis; Nucleophilic radiofluorination; PET; Radiochemistry