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

Abstract

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.

Synthesis of Bio-Based Thermoset Mixture Composed of Methacrylated Rapeseed Oil and Methacrylated Methyl Lactate: One-Pot Synthesis Using Formed Methacrylic Acid as a Continual Reactant

“…Generally, syntheses based on the usage of methacrylated anhydride use 4-dimethylaminopyridine (DMAP) as a catalyst [20][21][22][23]. However, this compound exhibits considerable toxicity [24] and it is also expensive. The present article describes the methacrylation process involving potassium 2-ethylhexanoate as a catalyst instead of the conventionally used DMAP-ethylhexanoic acid and potassium hydroxide, which are safer to handle during manufacturing processes [25] in comparison with DMAP [26].…”

One-Pot Reductive Methylation of Nitro- and Amino-Substituted (Hetero)Aromatics with DMSO/HCOOH: Concise Synthesis of Fluorescent Dimethylamino-Functionalized Bibenzothiazole Ligands with Tunable Emission Color upon Complexation

“…While the latter methodology is limited to the active C–X sites of heteroaromatic substrates, the former suffers from toxicity/carcinogenicity of given methylating reagents and their lower chemoselectivity, introducing the methyl group also to other Lewis-base centers, if available. Direct methylations of substrates possessing two or more nitrogen centers prone to electrophilic attacks (alkylation), such as important classes of aminopyridines or aminobenzazoles, are thus challenging …”

“…Direct methylations of substrates possessing two or more nitrogen centers prone to electrophilic attacks (alkylation), such as important classes of aminopyridines or aminobenzazoles, are thus challenging. 17 In this regard, more selective methylation of the amino group can be achieved by employing reductive alkylation with formaldehyde, 18 formic acid, 19 or CO 2 20 as the C 1 feedstocks, along with various reducing agents (hydrogen sources) ranging from formic acid (HCHO/HCOOH) in the Eschweiler−Clark reaction 21 through NaBH 4 22 or milder NaBH 3 CN 23 to molecular hydrogen (H 2 ), silanes, or boranes in conjunction with sophisticated transition-metal-based clusters and nanoparticles as hydrogenation catalysts. 18−20 methylation of amines can be performed by employing methanol 24 or methyl alkyl carbonates 25 as the carbon source.…”