Related Experiment Video
Updated: Sep 9, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
A Broadly Applicable Strategy to Aminate Azines Enabled by Electronically Tuned Phosphine Reagents
Ren-Rong Liu1, Jeffrey N Levy1, Andrew McNally1
1Department of Chemistry, Colorado State University, Fort Collins, CO, 80523, USA.
Abstract:
We describe a strategy for aminating pyridines and other azines via phosphonium salt intermediates. Precisely tuning the electronic properties of the phosphonium ion was key for C─N bond formation via an SNAr-halogenation, SNAr-amination sequence. The process couples a wide range of amine classes with pyridines and is viable for applications such as late-stage amination of complex pharmaceuticals and fragment-fragment coupling reactions. The capacity to rapidly modify the structure of the phosphine reagent was decisive and is a valuable feature in pseudohalide design.
Related Concept Videos
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Preparation of Amines: Reductive Amination of Aldehydes and Ketones
1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Mechanism
Preparation of Amines: Alkylation of Ammonia and Amines
Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

