Protonation and Basicity

Protonation or Lewis acid complexation of a heteroatom invites nucleophilic attack, including nucleophilic attack by a parent molecule. Oligomerization and polymerization are thus often the results of bringing heterocycles into an acid environment without making sure that all of the potentially nucleophilic sites are protonated. 

Alkylation, acylation, etc. at the heteroatom lead to onium salts. In small systems these are difficult to isolate, and very weakly nucleophilic counterions must be used, such as 

Heterocycle (kJmor ) Open chain analog (kJ raor ) 

In large rings the fate of the onium ions depends mostly on the structure and degree of unsaturation of the particular compound, and the onium salts range from completely stable to highly unstable. 

Electrophiles, such as C—Hal functions, contained in side chains may be well positioned for interaction with ring heteroatoms. Thus, Af-t-butyl-2-tosyloxymethylaziridine in ethanol displaces tosylate ion from the side chain, and nucleophilic opening of the resulting azabicyclobutanonium ion by solvent gives 3-hydroxy- and 3-ethoxy-azetidine (Section 5.09.2.3.2). 

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Electrophilic Attack on Ring Heteroatom 5.14.3.2.1 Protonation and basicity... 

Ruthenium complexes with mixed bipyridyl ligands, immobilized inside a Nation film, may also be used as pH-sensitive sensor layers [90]. A completely different approach for a ratiometric imaging of pH sensor foils was developed for diagenetic studies of marine sediments, using the dual fluorescence excitation ratio of the pH-sensitive fluorophore 8-hydroxypyrene-l,3,6-trisulfonic acid (HPTS) [91]. Commonly used dual fluorophors with different absorption and emission maxima in the protonated and basic form for ratiometric measurements are the naphthofluorescein and seminaphthofluorescein derivates (SNARF and SNAFL) [92], It should be noted that ammonia or carbon dioxide can also be detected by some of these pH-sensitive materials [55,93]. 

Protonation and basicity studies are reported in Section IV,B. Alkylations, like methylation, which proceed in the case of pyridazinones as N- and/or O-methylation, are treated in Section III,C. Only N-alkylations are mentioned in this section. 

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