Anomalies in isosterism

In this paragraph two applications of the bioisosterism concept that imply unusual behaviors of commonly encountered atoms or groups are discussed. 

There is a anomaly residing in the fact that fluorine does not resemble other halogens, notably chlorine, and that, on the other hand, it often mimics an atom of hydrogen.  

Steric aspects The fluorine atom is considerably smaller than the rest of the halogen atoms. Seen from the steric point of view it resembles more hydrogen than chlorine (Table 15.17). Effectively fluoro-derivatives differ from the other halogenated derivatives because fluorine forms with carbon particularly stable bonds and, in contrast to other halogens, is only rarely ionized or displaced. Because it is both chemically inert and of small size organic fluorine is often compared to hydrogen. 

One understands especially the incorporation by living organisms of fluoroacetic acid in place of acetic acid or of 5-fluoro-nicotinic acid and 5-fluoro-uracil as antimetabolites. This fraudulent incorporation leads to lethal syntheses. This is generally not the case with the corresponding chlorinated, brominated, or iodinated analogs. 

This explains among why para-fluorophenol is slightly less acidic than phenol while for other para-halogenated phenols the acidity changes in parallel with the atomic number (Table 15.18 ° ). 

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