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Cyclization of β‐Chlorovinyl Thiohydrazones into Pyridazines: A Mechanistic Study
Author(s) -
Komendantova Anna S.,
Fakhrutdinov Artem N.,
Menchikov Leonid G.,
Sukhorukov Alexey Yu.,
Zavarzin Igor V.,
Volkova Yulia A.
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201801118
Subject(s) - chemistry , isomerization , pyridazine , tautomer , thiol , computational chemistry , autocatalysis , medicinal chemistry , photochemistry , organic chemistry , catalysis
Extensive experimental and theoretical investigations on the isomerization and heterocyclizations of β‐chlorovinyl thiohydrazones derived from oxamic acid thiohydrazides and β‐chlorovinyl aldehydes were performed to elucidate the reaction mechanism of pyridazine formation. We showed that model β‐chlorovinyl thiohydrazone undergoes multiple isomerization reactions in solution induced by thione–thiol tautomerism and Z/E ‐isomerization at the C=N bond. Mechanistic rationalization along with computational studies demonstrated that pyridazine is predominantly generated from the Z ‐thiol isomers by 6 π‐electrocyclization of the thiohydrazone‐derived 2,3‐diazatriene intermediate. The autocatalytic character of cyclization accelerated by the formation of acid was demonstrated by means of 1 H NMR monitoring.