Optimized Synthesis of Di, Tri and Tetrafused Pyridazinium Cations

By combining two complementary statistical techniques (fractional factorial experimental design and simplex operation) the synthesis of the parent pyrido[1,2-b]-pyridazinium cation has been successfully carried out (the yield was improved from less than 10 to 65%) by basic condensation of 2-methyl-1-aminopyridinium mesitylenesulfonate and [1,4]dioxane-2,3-diol. Using the optimized reaction conditions, other related heterocyclic cations could be prepared, and two interesting examples are now reported.