Synthesis of Spiro-Pyrrolopyridazines

Dündar, Buse Ayşen
Heterocyclic molecules have great importance in organic chemistry due to their significant functions in very wide areas. Scientists tend to work on them because they exhibit excellent properties from medicine to material science. Especially, spiro class of heterocyclic molecules also have unique character among biological active compounds. Additon to spiro unit of molecules, fused systems also provide significant features to them. That’s why, spiro and fused systems are always popular subjects among organic chemists. In this thesis, the synthesis of a new family of heterotricyclic hybrids, spiro-pyrrolopyridazines, has been invetigated since such hybrid molecule may provide benefits for biological studies. With this aim, totally five steps were followed and 21 new derivatives of fused spiro-pyrrolopyridazines were synthesized with different electron-withdrawing and electron-donating groups. Firstly, synthesis of α,β-alkynic ketones by Sonogashira cross coupling of terminal alkynes with benzoyl chlorides were performed. Secondly, cyclohexane-embedded N-propargylic β-enaminones were obtained via conjugate addition of 1-ethylnylcyclohexylamine to α,β-alkynic ketones. Thirdly, cyclohexane-embedded N-propargylic β-enaminones were exposured to second Sonogashira cross coupling reaction with the corresponding aryl iodides to yield arylated β-enaminone derivatives. Forthly, spiro-2H-pyrroles, which are the starting compounds for the last step, were produced by the reaction between arylated cyclohexane-embedded N-propargylic β-enaminones and Cs2CO3 in DMSO. In the last step, a novel approach was enhanced for the synthesis of spiro-pyrrolopyridazines. For this purpose, spiro-2H-pyrroles with a 1,4-diketone group were treated with hydrazine monohydrate in refluxing n-butyl alcohol. At the final, 21 novel derivatives of previously unknown spiro-pyrrolopyridazine were synthesized in good to high yields.
Citation Formats
B. A. Dündar, “Synthesis of Spiro-Pyrrolopyridazines,” M.S. - Master of Science, Middle East Technical University, 2021.