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Preferential protonation and methylation at the nitrogen atoms of N , N ‐dimethylamino derivatives of pyridine
Author(s) -
Barbieri Giorgio,
Benassi Rois,
Grandi Romano,
Pagi Ugo Maria,
Taddei Ferdinando
Publication year - 1979
Publication title -
organic magnetic resonance
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.483
H-Index - 72
eISSN - 1097-458X
pISSN - 0030-4921
DOI - 10.1002/mrc.1270120307
Subject(s) - protonation , chemistry , steric effects , nitrogen , methylation , pyridine , reactivity (psychology) , ring (chemistry) , medicinal chemistry , molecule , derivative (finance) , stereochemistry , photochemistry , organic chemistry , medicine , ion , biochemistry , alternative medicine , pathology , financial economics , economics , gene
The relative reactivity toward protonation and methylation of the two nitrogen atoms in N , N ‐dimethylaminopyridines has been examined by 1 H NMR. The ring position of the dimethylamino group has no influence on protonation, which occurs in all the derivatives at the heterocyclic nitrogen. The N ‐methylation reaction does not follow a homogeneous behaviour, occurring at the exocyclic nitrogen in the 2‐substituted dimethylamino derivative. The electronic characteristics of the molecules, determined by MO calculations at a semi‐empirical level, indicate that both protonation and methylation should occur at the heterocyclic nitrogen; the calculated relative stabilites, however, of the N ‐protonated and N ‐methylated forms are in full agreement with the experimental results, and it appears that the anomalous behaviour of 2‐dimethylaminopyridine in the N ‐methylation reaction is caused by steric factors.