Details

Autor(en) / Beteiligte

• Halaszne Dajka, Beata

Titel

Synthesis of Polycyclic Pyridazines by Application of C-C Bond Formation Reactions. A Mechanistic Study of the Tert-Amino Effect

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2007

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• [d]-Annelated pyridazino ring systems are of great importance due to their valuable biological activities. One of the most efficient synthetic pathways to obtain such systems involves the type 2 tert-amino effect. (Thermal cyclization of ortho-vinyl-tert -anilines and their analogues.) In this way several, otherwise hardly accessible pyridazine derivatives could be prepared. The mechanism of the isomerization reaction was also investigated: effects of substituents at positions-4, -5 and -6; acyclic or cyclic electron-withdrawing groups at the vinyl moieties; amino substituents were studied. We also compared the influence of benzene and pyridazine ring on the reaction rate. Incorporation of the terminal vinylic carbon into a trioxopyrimidine ring accelerates the cyclization. Effects of substituents at the amino groups are also dependent on the arene ring. An aryl group at position-6 of the pyridazine ring increases the rate of the ring closure reaction. The presence of nitrogen atoms decreases the electronic density on the heterocyclic ring, thereby the pyridazinone derivatives cyclise slower than the benzene derivatives. Studies on deuterated derivatives confirmed an intramolecular pathway for rearrangement. Significant rate and yield enhancements were observed under solvent-free microwave and solvent-free conventional heating conditions. The pyridazino[4,5-b]indole ring system was prepared from pyridazinone precursors utilizing the combinations of a Buchwald-Hartwig amination with an intramolecular Heck-type reaction. The benzofurane analogue was synthesized via nucleophilic substitution reaction of 5-chloro-2-methyl-6-phenylpyridazin-3(2H)-one with phenol derivatives followed by Pd-catalyzed cyclodehydrohalogenation.