Quantification of the nucleophilic reactivity of nicotine

Abstract

Rate and equilibrium constants of the reactions of nicotine and structurally related compounds with benzhydrylium ions have been determined UV-Vis spectroscopically using stopped-flow and laser-flash techniques. The pyridine nitrogen of nicotine was identified as the site of thermodynamically and kinetically controlled attack. Quantum chemical calculations showed that the introduction of a pyrid-3-yl moiety into the 2-position of N-methylpyrrolidine (to give nicotine) reduces the Lewis basicity of the pyrrolidine ring by 24 kJ mol À1 , whereas the analogous introduction of a phenyl ring decreases this quantity by only 11 kJ mol À1 . Scheme 3. Reactions of nicotine (1a) with benzhydrylium ions 2h and 2q to give N-diarylmethylpyridinium salts (3h and 3q) Scheme 4. Reactions of (mfa) 2 CH + À BF 4 (2h) with (a) 3-methylpyridine (1b) to give pyridinium 5b and (b) N-methylpyrrolidine (1c) to give Ndiarylmethyl-N-methylpyrrolidinium salt 5c NUCLEOPHILIC REACTIVITY OF NICOTINE a The quoted values of N and s N for 1c were reported in ref. 8. NUCLEOPHILIC REACTIVITY OF NICOTINE

The McKenna reaction – avoiding side reactions in phosphonate deprotection

“…We [45,46]. On the other hand, the lower nucleophilicity of pyridine compared with the tertiary alkylamine present in compound 12 [45,46] may be responsible for the lower vulnerability of 9 towards alkylation.…”