Alkylpyridines alkylation, nucleophilic

As mentioned before, alkyl radicals and acyl radicals have a nucleophilic character therefore, radical alkylation and acylation of aromatics shows the opposite reactivity and selectivity to polar alkylation and acylation with the Friedel-Crafts reaction. Thus, alkyl radicals and acyl radicals do not react with anisole, but may react with pyridine. Eq. 5.1 shows the reaction of an alkyl radical with y-picoline (1). The nucleophilic alkyl radical reacts at the 2-position of y-picoline (1), where electron density is lower than that of the 3-position. So, 2-alkyl-4-methylpyridine (2) is obtained with complete regioselectivity. When pyridine is used instead of y-picoline, a mixture of 2-alkylpyridine and 4-alkylpyridine is obtained. Generally, radical alkylation or radical acylation onto aromatics is not a radical chain reaction, since it is just a substitution reaction of a hydrogen atom of aromatics by an alkyl radical or an acyl radical through the addition-elimination reaction. Therefore, the intermediate adduct radical (a complex) must be rearomatized to form a product and a hydrogen atom (or H+ and e ). Thus, this type of reactions proceeds effectively under oxidative conditions [1-6]. 

For describing the nucleophilicity of 2-alkylpyridines, Popov and Gelbina (770R145) proposed ortho-steric parameters N, but values given were limited to the a-alkyl series where good correlations are usually observed. 

Pyridinium salts show the properties which have been discussed above, but in extreme they are highly resistant to electrophilic substitution but, conversely, nucleophiles add very easily. The hydrogens of a- and 7-alkyl side-chains on pyridinium salts are further acidified compared with the uncharged alkylpyridine. 

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