A1 Refereed original research article in a scientific journal
A comparative study on the effect of solvent on nucleophilic fluorination with [F-18]fluoride: protic solvents as co-solvents in S(N)2 and SNAr reactions
Authors: Koivula T, Simecek J, Jalomaki J, Helariutta K, Airaksinen AJ
Publisher: WALTER DE GRUYTER GMBH
Publication year: 2011
Journal: Radiochimica Acta
Journal name in source: RADIOCHIMICA ACTA
Journal acronym: RADIOCHIM ACTA
Volume: 99
Issue: 5
First page : 293
Last page: 300
Number of pages: 8
ISSN: 0033-8230
DOI: https://doi.org/10.1524/ract.2011.1820
Abstract
The effect of solvent on nucleophilic substitution with cyclotron-produced [F-18]fluoride was studied in polar aprotic (CH3CN and DMF) and protic solvent (t-BuOH and t-amyl alcohol) mixtures (CH3CN/co-solvent, 2:8) in a series of model compounds, 4-(R-1-methyl)benzyl R-2-benzoates, using a K 2.2.2/[F-18]KF phase transfer system (R-1 = -Cl, -OMs or -OH; R-2 = -Cl, -I or -NO2). F-18-fluorination of compounds 1-3, with chloride or mesylate as a leaving group in the benzylic position (R-1), afforded the desired 4-([F-18]fluoromethyl)benzyl analogues in all solvents during 15 min reaction time. The highest radiochemical yields (RCY) in all the studied reaction temperatures (80, 120 and 160 degrees C) were achieved in CH3CN. Radiochemical yields in protic solvents were comparable to RCY in CH3CN only with the sulfonate ester 3 as a starting material. F-18-Fluorination of the benzylic halides 1 and 2 was not promoted in the same extent; in addition, labelled side-products were detected at higher reaction temperatures. Radiofluorination in tert-alcohols was also studied using [F-18]CsF with and without added phase transfer catalyst, resulting in both conditions lower RCY when compared to K 2.2.2/[F-18]KF system. Protic solvents were not able to promote aromatic F-18-fluorination. F-18-Fluorination of compound 5, having para-activated nitro group in the aromatic position (R-2), failed in tert-alcohols even at the highest temperature, but it was labelled successfully in DMF and to some extent in CH3CN.
The effect of solvent on nucleophilic substitution with cyclotron-produced [F-18]fluoride was studied in polar aprotic (CH3CN and DMF) and protic solvent (t-BuOH and t-amyl alcohol) mixtures (CH3CN/co-solvent, 2:8) in a series of model compounds, 4-(R-1-methyl)benzyl R-2-benzoates, using a K 2.2.2/[F-18]KF phase transfer system (R-1 = -Cl, -OMs or -OH; R-2 = -Cl, -I or -NO2). F-18-fluorination of compounds 1-3, with chloride or mesylate as a leaving group in the benzylic position (R-1), afforded the desired 4-([F-18]fluoromethyl)benzyl analogues in all solvents during 15 min reaction time. The highest radiochemical yields (RCY) in all the studied reaction temperatures (80, 120 and 160 degrees C) were achieved in CH3CN. Radiochemical yields in protic solvents were comparable to RCY in CH3CN only with the sulfonate ester 3 as a starting material. F-18-Fluorination of the benzylic halides 1 and 2 was not promoted in the same extent; in addition, labelled side-products were detected at higher reaction temperatures. Radiofluorination in tert-alcohols was also studied using [F-18]CsF with and without added phase transfer catalyst, resulting in both conditions lower RCY when compared to K 2.2.2/[F-18]KF system. Protic solvents were not able to promote aromatic F-18-fluorination. F-18-Fluorination of compound 5, having para-activated nitro group in the aromatic position (R-2), failed in tert-alcohols even at the highest temperature, but it was labelled successfully in DMF and to some extent in CH3CN.
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