Synthesis of Pyrazolopyridin-3-ones by Cyclization of 3-Acylpyridine N-Oxide Tosylhydrazides
Poster Number
35
College
College of Arts and Sciences
Department
Chemistry, Physics, Geology, & the Environment
Faculty Mentor
James M. Hanna, Jr., Ph.D.
Abstract
Pyrazolopyridinones are fused heterocyclic compounds that contain a pyridine ring as part of the fused bicyclic system. Pyrazolopyridinones are currently studied for their link to a range of biological activities, including antiviral, antitumor, anti-hypertensive, anti-anxiety, and cardiotonic agencies. Previously, the Hanna group investigated the use of tosylhydrazones formed using 3-acylpyridine N-oxides, and discovered that the N-oxides can be cyclized to pyrazolopyridines. We sought to exploit the chemistry behind that cyclization for the synthesis of pyrazolopyridinones. We began with the synthesis of pyridine 3-carboxylic acid N'-tosylhydrazide, which was achieved in 79 % yield. Initial attempts at oxidation using the Sharpless method of aqueous hydrogen peroxide and methyltrioxorhenium (MTO) in dichloromethane (DCM) were unsuccessful, presumably due to insolubility of the starting hydrazide. Through an adaptation of this method using urea hydrogen peroxide and MTO in ethanol, the tosylhydrazide was successfully oxidized to its N-oxide with a yield of 75 %. Cyclization was attempted under several different sets of conditions, and the results of these experiments will be presented.
Start Date
24-4-2015 1:20 PM
End Date
24-4-2015 2:50 PM
Synthesis of Pyrazolopyridin-3-ones by Cyclization of 3-Acylpyridine N-Oxide Tosylhydrazides
Richardson Ballroom
Pyrazolopyridinones are fused heterocyclic compounds that contain a pyridine ring as part of the fused bicyclic system. Pyrazolopyridinones are currently studied for their link to a range of biological activities, including antiviral, antitumor, anti-hypertensive, anti-anxiety, and cardiotonic agencies. Previously, the Hanna group investigated the use of tosylhydrazones formed using 3-acylpyridine N-oxides, and discovered that the N-oxides can be cyclized to pyrazolopyridines. We sought to exploit the chemistry behind that cyclization for the synthesis of pyrazolopyridinones. We began with the synthesis of pyridine 3-carboxylic acid N'-tosylhydrazide, which was achieved in 79 % yield. Initial attempts at oxidation using the Sharpless method of aqueous hydrogen peroxide and methyltrioxorhenium (MTO) in dichloromethane (DCM) were unsuccessful, presumably due to insolubility of the starting hydrazide. Through an adaptation of this method using urea hydrogen peroxide and MTO in ethanol, the tosylhydrazide was successfully oxidized to its N-oxide with a yield of 75 %. Cyclization was attempted under several different sets of conditions, and the results of these experiments will be presented.
