title: The use of tetrabutylammonium fluoride to promote N- and O-(11) C-methylation reactions with iodo[(11) C]methane in dimethyl sulfoxide.
abstract: The N- or O-methylation reactions of compounds bearing amide, aniline, or phenol moieties using iodo[(11) C]methane (1) with the aid of a base are frequently applied to the preparation of (11) C-labeled radiopharmaceuticals. Although sodium hydride and alkaline metal hydroxides are commonly employed as bases in these reactions, their poor solubility properties in organic solvents and hydrolytic activities have sometimes limited their application and made the associated (11) C-methylation reactions difficult. In contrast to these bases, tetrabutylammonium fluoride (TBAF) is moderately basic, highly soluble in organic solvents, and weakly nucleophilic. Although it was envisaged that TBAF could be used as the preferred base for (11) C-methylation reactions using 1, studies concerning the use of TBAF to promote (11) C-methylation reactions are scarce. Herein, we have evaluated the efficiency of the (11) C-methylation reactions of 13 model compounds using TBAF and 1. In most cases, the N-(11) C-methylations were efficiently promoted by TBAF in dimethyl sulfoxide at ambient temperature, whereas the O-(11) C-methylations required heating in some cases. Comparison studies revealed that the efficiencies of the (11) C-methylation reactions with TBAF were comparable or sometimes greater than those conducted with sodium hydride. Based on these results, TBAF should be considered as the preferred base for (11) C-methylation reactions using 1.
authors.affiliation: Molecular Probe Program, Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Minegishi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D008745:Methylation; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*
chemical_list: D002250:Carbon Radioisotopes; D000644:Quaternary Ammonium Compounds; C009405:tetrabutylammonium; D004121:Dimethyl Sulfoxide
keywords: amide; aniline; carbon-11; iodomethane; isotopic labeling; methylation; phenol; tetrabutylammonium fluoride