Strategies for the Synthesis of N-Arylammonium Salts

Abstract

The N-arylation of tertiary amines to provide sp3 quaternary ammonium salts is a challenge in organic chemistry. To date, no general method for such arylations has been established. Here, we summarize a variety of strategies that have been tested, starting with harsh nucleophilic aromatic substitutions, through to the use of copper catalysis and the application of strong electrophiles, such as phenyl cations and benzynes. The achievements and limitations of each method are summarized, and the challenges yet to be met in the synthesis of charged ammonium compounds are described.1 Introduction2 Alkylation of Anilines: The Menshutkin Reaction3 Arylations3.1 Nucleophilic Aromatic Substitutions by Tertiary Amines3.2 Preparation of N-Arylpyridinum Salts from Zincke and Pyrylium Salts3.3 Arylations Using Phenyl Cations3.4 Copper-Catalyzed Arylation of N-Heteroarenes3.5 Benzynes as Aryl Electrophiles4 Conclusions and Perspective

Harnessing the High Interfacial Electric Fields on Water Microdroplets to Accelerate Menshutkin Reactions

“…The Menshutkin reaction is an important alkyl-transfer reaction with wide applications in chemical synthesis , and biochemical processes, such as histone methylation and methyltransferases. , This special class of S N 2 reaction converts a tertiary amine into a quaternary ammonium salt by reaction with an alkyl halide (Scheme ). The gas-phase Menshutkin reaction is generally endothermic.…”

Synthesis of Complex Diarylamines through a Ring‐Opening Difunctionalization Strategy**

“…Diarylammonium salts 4 are potentially interesting compounds since organic ammonium salts find various industrial applications [18a] owing to their antimicrobial, [24] antistatic [25] and surfactant [25a,26] properties. To demonstrate the efficient preparation of 4 , a small set of these products were isolated in 65–99 % yield by simple evaporation of the solvent (Scheme 5).…”

Synthesis of Highly Functionalized Diarylamines through an N-, C-Cascade Reaction via Ammonium Salts

“…The synthesis of organic ammonium salts is generally difficult, and only a few examples are known in literature. 16 Our key intermediate, ammonium salt 4, could be particularly challenging due to the high steric congestion from the two aryl moieties as well as the large ortho-iodo substituent. To our delight, the reaction proved to be possible using a mild base and no excess reagents, by heating salt 3a in MeCN at 100 °C for 4 h followed by reaction with K2CO3 and piperidine at rt for 2 h, to provide 5a as the only product in 47% yield (entry 1).…”

“…We anticipate that products 9 and 10 stem from an iminium intermediate formed through the ring opening of 4a by DMF in similarity with the Vilsmeier-Haack intermediate 20 (see SI section 3.3). Ammonium salt 4 are potentially interesting compounds since organic ammonium salts find various industrial applications 16 owing to their antimicrobial, 21 antistatic 22 and surfactant 22a, 23 properties. To demonstrate the efficient preparation of 4, a small set of these products were synthesized by heating of 3, and isolated in good to excellent yields by simple evaporation of the solvent (Scheme 5).…”