Tetrabutylammonium salt induced denitration of nitropyridines: synthesis of fluoro-, hydroxy-, and methoxypyridines.
An efficient method for the synthesis of fluoropyridines via the fluorodenitration reaction is reported. The reaction is mediated by tetrabutylammonium fluoride (TBAF) under mild conditions without undue regard to the presence of water. The fluorodenitration is general for 2- or 4-nitro-substituted pyridines, while 3-nitropyridines require attendant electron-withdrawing groups for the reaction to proceed efficiently. Nitropyridines also undergo hydroxy- and methoxydenitration under mild conditions in the presence of the corresponding tetrabutylammonium species. [reaction: see text]
Kuduk
Scott D
SD
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. scott_d_kuduk@merck.com
DiPardo
Robert M
RM
Bock
Mark G
MG
D008958:Models, Molecular; D009566:Nitrates; D009574:Nitro Compounds / Q000737:chemistry*; D011725:Pyridines / Q000138:chemical synthesis*; D000644:Quaternary Ammonium Compounds
D009566:Nitrates; D009574:Nitro Compounds; D011725:Pyridines; D000644:Quaternary Ammonium Compounds; C009405:tetrabutylammonium