General and Highly Efficient Syntheses of m-Fluoro Arenes Using Potassium Fluoride-Exchange Method

Abstract

Tetraphenylphosphonium bromide was found to be a suitable catalyst for the reaction of m-nitroaryl derivatives carrying cyano, nitro, chlorocarbonyl, trifluoromethyl, and chlorosulfonyl groups with potassium fluoride in the presence of a stoichiometric amount of phthaloyl dichloride, giving the corresponding m-fluoro aromatic derivatives in good yields. The catalyst was also found to be efficient for the fluorodesulfonylation of m-(fluorosulfonyl)aryl derivatives to afford m-fluoro arenes by the use of a reaction-distillation technique.

Syntheses of meta‐[18F]fluorobenzaldehyde and meta‐[18F]fluorobenzylbromide from phenyl(3‐Formylphenyl) iodonium salt precursors

“…Although ortho‐ and para‐ [ 18 F]fluorobenzaldehydes can easily be prepared with high yields by nucleophilic substitution reactions where corresponding nitro groups or quaternary amines are replaced by [ 18 F]F − , the corresponding meta‐ derivatives are more problematic. Sometimes, meta‐ [ 18 F]fluorobenzaldehyde is needed in order to prepare radiopharmaceuticals with an exact molecular structure of interest and current yields obtained for meta‐ [ 18 F]fluorobenzaldehyde from meta‐ nitrobenzaldehyde are very low25–27 because the meta ‐position of benzaldehyde is comparatively electron rich. Nucleophilic [ 18 F]F − radiolabeling of such non‐activated aromatic rings can be carried out by introducing an activating group with its removal or modification after labeling 28, 29.…”

Nucleophilic Fluorination of Electron-Deficient Arenes

“…Accordingly, the reactions usually require high temperature and long reaction time to achieve high yields and complete conversion. Moreover, the use of spray-dried KF to increase its surface area [17,18] and the addition of phase transfer catalysts including quaternary ammonium salts, quaternary phosphonium salts, and crown ethers have been shown to be advantageous in increasing the yields (Scheme 5) [14,16,[19][20][21][22][23][24][25][26][27]. A combination of KF, tetraphenylphosphonium bromide, and 18-crown-6 has been successfully used to convert chlorobenzaldehydes to the corresponding fluorobenzaldehydes (Scheme 5, Eq.…”

“…It was found that in S N Ar fluorination of nitroarenes with KF, the addition of phthaloyl dichloride (PDC) is beneficial for the reaction (Scheme 5, Eq. 6) [25]. It was assumed that the role of PDC is an in situ trap of nitrite anions (NO 2 À ) displaced during the reaction [25].…”

“…6) [25]. It was assumed that the role of PDC is an in situ trap of nitrite anions (NO 2 À ) displaced during the reaction [25]. As an additional role, it was suggested that PDC may serve as a water scavenger, which can remove a trace amount of water in the reaction system [7].…”

Fluorine-18 labelled building blocks for PET tracer synthesis

“…Attempts to prepare 3-[ 18 F]fluorobenzaldehyde from nitro-or trimethylammonium benzaldehyde precursors resulted in very low radiochemical yields. [245][246][247] For the synthesis of 3-[ 18 F]fluorobenzaldehyde in higher radiochemical yields, various new radiofluorination techniques have recently been investigated (Scheme 71). 18,28,34,35 243,[249][250][251][252][253][254][255][256] Except for tracer 365, in which sodium borohydride was used as a reductant at 60 1C and tracers 366a and 366b, in which sodium triacetoxyborohydride was used as a reductant at room temperature, all tracers were produced using sodium cyanoborohydride as the reductant at temperatures 4100 1C.…”