The Effect of Aliphatic Fluorine on Amine Drugs
1976; American Chemical Society; Linguagem: Inglês
10.1021/bk-1976-0028.ch005
ISSN1947-5918
AutoresRay W. Fuller, Bryan B. Molloy,
Tópico(s)Chemical Reactions and Mechanisms
ResumoFluorine is the most electronegative element (1) (Table I), and its presence in a molecule can greatly affect the ionization of acids and bases (2). The withdrawal of electrons toward fluorine on a carbon atom adjacent to a carboxyl carbon or an amino-bearing carbon increases the carboxyl group's ability to release a proton and decreases the amine's ability to accept a proton. The carboxylic acid becomes a stronger acid, and the amine becomes a weaker base. For example, the pKa of ethylamine is >10 compared to 5.7 for β,β,β-trifluoroethylamine (3). We have studied some sympathomimetic amine drugs having reduced basicity due to fluorine substituted on the β carbon. The influence of ionization on the activity of sympathomimetic amines has previously been considered (4), but with the exception of compounds having substituents directly on the nitrogen, no such amines having pKa values below physiological pH appear to have been available (5).
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