Cyanostar Synthesis on Large Scales in 2 Weeks and Small Scales in 2 Days

Cyanostar is a pentagonal anion-binding macrocycle that is selective for polyatomic anions including hexafluorophosphate (PF6–), organophosphates (RHPO4–), and organic anions like tetrazine radicals. Use of cyanostar in research and technology has grown since its debut in 2013 with more than 40 publications and 5 patents spanning recognition, sensing, dynamic polymers, reversible adhesives, semi-conductor dopants, and programmable optical materials. However, the optimized synthesis and purification of cyanostar that developed over the years has yet to be published. The preparation of cyanostar reported here begins with commercially available 5-tert-butylisophthalic acid. From this starting material, cyanostar can be synthesized in good yield in 6 steps on large scales or in just 5 steps on expedited smaller scales. On large scales, high yields are maintained at each step and cyanostar is produced in a 50% yield over the course of 2 weeks. The small-scale synthesis produces cyanostar in a 3% yield but can be completed in just 2 days. These syntheses put lessons from sophomore organic chemistry and macrocycle chemistry into practice. Herein, we present a step-by-step guide toward easy and reliable synthesis of cyanostar at both scales and provide a comparison of hazards, reaction times, and overall yields for these methods.