 The Kröhnke method in this synthesis was crucial due to the failure of other cyclization techniques such as the Glaser coupling or Ullmann coupling.Another use of the Kröhnke pyridine synthesis was the generation of a number of 2,4,6-trisubstituted pyridines that were investigated as potential topoisomerase 1 inhibitors.2-acetylthiophene (46) was treated with iodine and pyridine to generate α-pyridinium acyl ketone 47.