This systematic study describes the preparation of bifunctional n. c. a. 8F-f luoroalkanes using aminopolyether (APE) supported nucleophilic substitution. With the APE (Kryptof ix@ 2.2.2. ) potassium carbonate complex in acetonitrile n.c.a. into disubstituted alkanes ( X(CH2)nX, n = 1-3, X = Br, OMes, OTos ) in high yields within 10-15 min. The substitution yield increases in the sequence of leaving groups Br < OMes < OTos and with increasing alkyl chain length. At substrate concentrations of 0 . 0 2 5 M of bistosyloxyethane a radiochemical yield of 8 2 2 8% of [1-18F]-fluoroethyltosylate is obtained.This compound appears optimal as fluoroalkylation agent with respect to size, stability and ease of its preparation. 8F-is introduced

SUMMARYThe fluoroalkylation of H-acidic compounds in the presence of the aminopolyether 2.2.2./potassium carbonate complex was systematically studied. With acetonitrile as solvent nucleophilic fluorination and subsequent fluoroalkylation can be carried out in a one-pot mode. Using the bifunctional fluoroalkanes 18F(CH2)nX (n = 1-3, X = Br, OMes, OTos) the best n.c.a. labelling yields were obtained with tosylates. Fluoroethylation and fluoropropylation of phenol gave rise to radiochemical yields of 2 90% under optimized conditions within 10 min. The fluoroethyl moiety is the smallest generally applicable fluoroalkylation agent. In a series of H-acidic compounds a strong influence of their pKa value on the fluoroethylation reaction was observed. Besides H-acidic compounds all Lewis bases are principally potential substrates for n.c.a. 18F-fluoroalkylation.

The preparation and introduction of fluoroacyl moieties as prosthetic groups is described for n.c.a. labelling with fluorine‐18. Activation by the aminopolyether 2.2.2./K2CO3 complex was used for the nucleophilic 18F‐exchange in α‐substituted acid esters. Increasing yields were found in the sequence: iodo << chloro < tosyloxy < bromo. The methylester of α‐bromopropionic acid proved to be the best precursor for acylation. The [2‐18F]fluoropropionic acid methylester was prepared with radiochemical yields of > 90% within 10 minutes. It reacted effectively with primary alcohols in the presence of 3% methane sulfonic acid. Using n‐butylamine as model compound and O.1% NH4Cl as acid in aqueous solution, n.c.a. N‐fluoroacylation was also performed with > 80% radiochemical yield. This reaction is relevant to 18F‐labelling of biomolecules such as peptides.

The nucleophilic introduction of n.c.a. ‐ [18F]‐fluoride into alkanes and carboxylic acids using anion activation by macrocyclic polyethers was investigated. The reactions carried out in the presence of the bicyclic aminopolyether APE 2.2.2. gave rise to high radiochemical yields (40‐65 %) under mild conditions. Important for the successful 18F‐labelling is a suitable cation/polyether couple, which leads to an unsolvated [18F]‐fluoride in a dipolar aprotic solvent and ensures a high ion concentration, thus enhancing the reactivity. Reaction parameters, such as concentration of substrate and APE, the influence of cation, anion and water were studied and optimised.