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

作者：Pritchard Ruth; Kilner Colin A; Halcrow Malcolm A^*

来源：Tetrahedron Letters, 2009, 50(21): 2484-2486.

DOI：10.1016/j.tetlet.2009.03.035

• Indazolylpyridines
• Nucleophilic substitution
• Regiochemistry
• Crystal structure

Reaction of 2-bromopyridine with 2 equiv of sodium indazolide in diglyme at 140 degrees 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 inclazolide at 70 degrees 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 I equiv of sodium pyrazolide in diglyme at 140 degrees 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 inclazolide 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.

• 出版日期2009-5-27