Monoselective Mechanochemical Aromatic Nucleophilic Substitution Enabled by Crystal-Engineering-Guided Reaction...

Area of Science:

• Organic Chemistry
• Solid-State Chemistry
• Sustainable Synthesis

Background:

• Mechanochemistry offers sustainable and efficient synthetic routes.
• Solid-state reactions show unique reactivity compared to solution-phase methods.
• Designing selective solid-state reactions remains a challenge.

Purpose of the Study:

• To develop a crystal-engineering approach for selective mechanochemical reactions.
• To achieve site- and chemoselective nucleophilic aromatic substitution (S_NAr) in the solid state.
• To contrast solid-state selectivity with solution-phase reactivity.

Main Methods:

• Mechanochemical ball milling for solid-state reactions.
• Organic crystal engineering principles.
• Single-crystal X-ray diffraction for structural analysis.

Main Results:

• Solid-state S_NAr reactions of perfluoroarenes with carbazoles selectively produced monosubstituted products.
• Solution-phase reactions yielded mixtures of mono- and disubstituted products.
• X-ray diffraction revealed π-π interactions stabilizing the products and preventing further reaction.

Conclusions:

• Crystal engineering enables highly selective solid-state organic transformations.
• Mechanochemical S_NAr reactions offer superior monoselectivity over solution-based methods.
• This approach provides a new strategy for designing difficult-to-achieve selective solid-state syntheses.