Solvent-Free Synthesis of Diazocine

Dedicated to Professor Herbert Mayr on the occasion of his 70^th birthday

Abstract

A convenient two-step synthesis of diazocine starting from 2-nitrotoluene is described. The first step, the oxidative dimerization of 2-nitrotoluene, is improved to 95% yield. The second step, the reductive azo cyclization, is performed as a solvent-free reaction with lead powder in a ball mill (51% yield). As a reference, the previously described azo cyclization with Zn/Ba(OH)₂ is investigated in detail. The results explain why in previous experiments the yields are low and extremely dependent on the reaction conditions. In view of potential applications in photopharmacology, we checked the stability under reducing conditions. Diazocine does not react with glutathione, indicating intracellular stability.

Key words

bridged azobenzene - diazocine - reductive azo-cyclization - solvent-free synthesis - oxidative C–C coupling - lead - azoxy - hydrazine - glutathione

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