Mechanochemical S <i> _N </i> Ar on Phthalonitriles: Distinct Reactivity and Selectivity in One‐Pot Synthesis for Greener Phthalocyanines

Traditional syntheses of functionalized phthalonitriles and phthalocyanines (Pcs) rely on solution‐phase nucleophilic aromatic substitution (S N Ar) in high‐boiling polar aprotic solvents, raising sustainability and safety concerns. Herein, we establish mechanochemical S N Ar under liquid‐assisted grinding (LAG) as a robust and versatile platform for the solvent‐minimized functionalization of phthalonitriles. Systematic optimization of base loading, ambient moisture, milling time, and LAG volume ( η ) enables highly reproducible, high‐yielding reactions at η values as low as 0.03 µL mg −1 , four orders of magnitude lower than traditional synthesis. A broad scope of seven nucleophiles and nine electrophiles gives mono‐, di‐, and tetrasubstituted phthalonitriles, typically in near‐quantitative conversion and without chromatographic purification. Mechanochemical conditions also unlock distinct reactivity. Product distributions in pyridyloxy systems can be tuned between keto‐ and enol‐derived isomers by adjusting η , and optimized reaction of 4,5‐dichlorophthalonitrile affords quantitative and highly selective monosubstitution, enabling controlled access to asymmetric phthalonitriles. The mechanochemical synthesis of phthalonitriles is directly integrated with solid‐state cyclotetramerization, either in sequential steps or in a one‐pot S N Ar–cyclotetramerization protocol, yielding a broad range of Pc substitution patterns and chemistries. The one‐pot process provides a scalable and sustainable route to advanced Pc architectures.