Unexpected product distributions in the synthesis of 2,6-bis-(indazolyl)pyridine and 2-(pyrazol-1-yl)-6-(indazolyl)pyridine

Reaction of 2-bromopyridine with 2 equiv of sodium indazolide in diglyme at 140 °C affords 2,6-bis-(indazol-1-yl)pyridine and 2-(indazol-1-yl)-6-(indazol-2-yl)pyridine in purified yields of 24% and 68% respectively. A similar reaction, using 1 equiv of sodium indazolide at 70 °C, gives a low-yield mixture of 2-(indazol-1-yl)-6-bromopyridine and 2-(indazol-2-yl)-6-bromopyridine. Both these intermediates are transformed into 2-(pyrazol-1-yl)-6-(indazol-1-yl)pyridine and 2,6-di(pyrazol-1-yl)pyridine upon treatment with 1 equiv of sodium pyrazolide in diglyme at 140 °C. These observations imply that the indazolyl group is a leaving group comparable to a bromo substituent under nucleophilic attack by pyrazolide or indazolide ions under these conditions. No reaction was observed between 2-(pyrazol-1-yl)-6-bromopyridine and 1 equiv of sodium indazolide under the same conditions. A single crystal structure of its iron(II) complex confirmed the regiochemistry of 2,6-bis-(indazol-1-yl)pyridine, and revealed significant conformational flexibility in the distal ligand indazolyl groups.