The Contrasting Alkylations of 4-(Dimethylaminomethyl)pyridine and 4-(Dimethylamino)pyridine: An Organic Chemistry Experiment

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A critical factor for the increased nucleophilicity of the pyridine nitrogen in 4-(dimethylamino)pyridine (DMAP) is electron donation via resonance from the amino group into the aromatic ring that increases electron density on the pyridine nitrogen. To explore how important this resonance effect is, 4-(dimethylaminomethyl)pyridine (DMAMP) was synthesized and the alkylation products of DMAP and DMAMP were compared. The methylene group between the pyridine ring and the amino group in DMAMP removes the possibility of resonance effects between the two nitrogen atoms. Alkylation of DMAP occurs exclusively at the pyridine nitrogen, whereas alkylation of DMAMP occurs exclusively at the amino group indicating that resonance effects are quite important. When these alkylations are carried out with a 1:1 equimolar ratio of CH3I and CH3CH2I, only methylated products are formed. This laboratory experiment is designed to teach students how to analyze the fundamental concepts of nucleophilicity and electrophilicity as a method of accurately predicting the reactivity of organic compounds. Molecular orbital calculations are used to examine the electron density present on each nitrogen atom of DMAP and DMAMP (as a measure of nucleophilicity) and to determine the stability of the possible products.