Oxidation of substituted 4-fluorobenzaldehydes: application to the no-carrier-added syntheses of 4-[18F]fluoroguaiacol and 4-[18F]fluorocatechol.
The synthesis of 4-[18F]fluoroguaiacol (4-[18F]fluoro-2-methoxyphenol) has been achieved in no-carrier-added form starting from 2-methoxy-4-nitrobenzaldehyde, using nucleophilic aromatic substitution by [18F]fluoride followed by Baeyer-Villiger oxidation of the benzaldehyde to the phenol. Demethylation with boron tribromide gave 4-[18F]fluorocatechol (1,2-dihydroxy-4-[18F]fluorobenzene) with an overall yield of 18-28% (EOB) in less than 2 h synthesis time. The fluorine-18 labeled intermediates and products were identical to standards of 4-fluoroguaiacol and 4-fluorocatechol prepared by the same methods. This represents a new approach to the synthesis of fluorinated phenols in fluorine-19 and fluorine-18 forms.
Chakraborty
P K
PK
Department of Internal Medicine, University of Michigan, Ann Arbor 48109.
Kilbourn
M R
MR
D002396:Catechols / Q000138:chemical synthesis*; D005462:Fluorine Radioisotopes; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D010084:Oxidation-Reduction
D002396:Catechols; D005462:Fluorine Radioisotopes; C072305:4-fluorocatechol; C072304:4-fluoroguaiacol; D006139:Guaiacol