A facile synthesis of a novel family of heterotricyclic hybrids: Spiro-pyrrolopyridazines

An efficient strategy for the synthesis of spiro-pyrrolopyridazines has been developed. When reacted with hydrazine monohydrate, spiro-2H-pyrroles with a 1,4-diketone functionality produced a novel family of heterotricyclic hybrids, spiro-pyrrolopyridazines, specifically spiro{cyclohexane-1,5'-pyrrolo[3,4-d]pyridazine} systems. The condensation reaction of spiro-2H-pyrroles with hydrazine monohydrate in refluxing 1-butanol proceeded well and afforded spiro-pyrrolopyridazines in good to high yields. The reaction was found to be general for variety of spiro-2H-pyrroles and demonstrated good tolerance to a variety of aromatic and heteroaromatic groups with electron-withdrawing and electron-donating substituents. The synthesis of heterotricyclic spiro-pyrrolopyridazine hybrids may exhibit potential to deliver diverse structural motifs that aid the drug discovery efforts.


A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic beta-enaminones
Ibis, Ozge; Zora, Metin (Elsevier BV, 2020-11-01)
A new and efficient method for the synthesis of 6-chloro-substituted 2-methylene-2,3-dihydro-1,4-oxazepines has been demonstrated. Upon treatment with N-chlorosuccinimide in acetonitrile, N-propargylic beta-enaminones underwent chlorination to afford alpha-chlorinated N-propargylic beta-enaminones, which was then subjected to electrophilic cyclization with zinc chloride in refluxing chloroform to yield 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines. It was shown for the first time that on N-propargylic bet...
A new approach for the synthesis of spiro and gem-dimethyl-substituted 1,4-oxazepines from N-propargylic beta-enaminones
Karadeniz, Eda; Kelgökmen, Yılmaz; Zora, Metin (Wiley, 2020-11-01)
An efficient and general method for the synthesis of spiro-1,4-oxazepines and 3,3-dimethyl-1,4-oxazepines is reported. When treated with ZnI2 and AgSbF6 in refluxing DCE, cyclohexane-embedded N-propargylic beta-enaminones underwent 7-exo-dig cyclization to afford spiro-1,4-oxazepines, specifically 12-methylene-11-oxa-7-azaspiro[5.6]dodeca-7,9-dienes, in good to high yields. Accordingly, N-(1,1-dimethyl)propargylic beta-enaminones produced 3,3-dimethyl-1,4-oxazepines. Cyclization was found to be general for ...
Concise design and synthesis of pyridine-fused heterocycles via 6 pi- Azaelectrocyclization process of iminoalkyne derivatives
Sendil, Kivilcim; Keskin, Selbi; Balcı, Metin (Elsevier BV, 2019-11-15)
A concise and regioselective approach to the synthesis of pyridine-fused heterocycles and benzoxazepine derivatives was developed. Propargyl imines derived from aromatic aldehydes and propargyl amine underwent 6 pi-electrocyclization reactions at high temperatures in high yields to form pyridine-fused heterocycles. Application of the same methodology to aromatic imines having a hydroxyl group in the ortho position resulted in the formation of (benz)oxazepine derivatives. The formation mechanism of the produ...
Synthesis of thienopyridinones via hydrazide-alkyne cyclization
Cokol, Nalan Korkmaz; Erden, Kübra; Gunay, Furkan Melih; Dengiz, Çağatay; Balci, Metin (Elsevier BV, 2020-05-08)
A novel and efficient method for the synthesis of thieno[3,2-c]pyridinones have been developed. The synthetic strategy relies on the synthesis of halothiophene esters utilized as substrates for subsequent Sonogashira cross-coupling reactions. Hydrazinolysis of corresponding esters and following hydrazidealkyne ring closure transformations resulted in target thienopyridinones in good yields. It is also shown that pure hydrazine monohydrate is required to facilitate the hydrazide formations.
A New Strategy for the Synthesis of 4-Propargyl-Substituted 1H-Pyrroles from N-(5-phenyl-2,4-pentadiynyl) beta-Enaminones
Yılmaz, Elif Serel; Zora, Metin (2019-10-09)
A new method for the synthesis of 4-propargyl-substituted 1H-pyrroles is described. When treated with sodium hydride in refluxing dichloromethane, N-(5-phenyl-2,4-pentadiynyl) beta-enaminones, synthesized by the coupling of N-propargylic beta-enaminones with phenylacetylene, afforded 4-propargyl-substituted pyrrole derivatives. This conversion was general for a variety of N-(5-phenyl-2,4-pentadiynyl) beta-enaminones and displayed broad functional group tolerance. During the reaction, not only cyclization of...
Citation Formats
B. A. Dündar and M. Zora, “A facile synthesis of a novel family of heterotricyclic hybrids: Spiro-pyrrolopyridazines,” SYNTHETIC COMMUNICATIONS, pp. 0–0, 2022, Accessed: 00, 2022. [Online]. Available: https://hdl.handle.net/11511/95407.