Synthesis of Isomeric Isothiazolo[4′,3′:4,5]- and Isothiazolo[4′,5′:4,5]thieno[3,2-b]pyrano[2,3-d]pyridines by Combination of Domino Reactions

Abstract

Isothiazolothienopyridines have been prepared by a domino reaction (the SN2 reaction → the Thorpe-Ziegler reaction → the Thorpe-Guareschi reaction type) from disodium 4-cyanoisothiazole-3,5-dithiolate. By changing the order of addition of the alkylation reagents in the reaction with disodium 4-cyanoisothiazole-3,5-dithiolate both possible isomers of the isothiazolothienopyridines are synthesized. These isomers were further used in three-component domino reaction (the Knoevenagel reaction → the Michael reaction → the hetero-Thorpe-Ziegler reaction type) to obtain wide range of isomeric isothiazolothienopyranopyridines.

Crystal structure of 8-[7,8-bis(4-chlorobenzoyl)-7H-cyclopenta[a]acenaphthylen-9-yl]naphthalene-1-carboxylic acid

“…In this reaction, multiple C-C or C-H bonds are formed in the same vessel, including different reaction mechanisms to form complex molecules without the purification of intermediates. These reactions are often used in medical or combinatorial chemistry to synthesize complex active drug molecules (Sudhapriya et al, 2014;Tietze et al, 2014;Fu et al, 2013;Shestopalov et al, 2013;Zohreh & Alizadeh, 2013;Renault et al, 2007). Domino reactions are classified as homo-domino processes and hetero-domino processes (Nesi et al, 1999).…”

Temperature-Controlled Thiation of α-Cyano-β-Alkynyl Carbonyl Derivatives for De Novo Synthesis of 2-Aminothiophenes and Thieno[2,3-c]isothiazoles

“…At elevated temperatures (130 °C), the LR-mediated reaction in p -xylene could furnish an unexpected product 4a in 58% yield (entry 6), the structure of which was unambiguously determined by X-ray crystallographic analysis as a substituted thieno­[2,3- c ]­isothiazole . To our knowledge, only a few synthetic approaches were reported to synthesize thieno­[2,3- c ]­isothiazole scaffolds. − Among them, Gewald and co-workers had described the first synthesis of thieno­[2,3- c ]­isothiazoles involving a three-step sequence through an oxidative ring closure of 2-amino-3-thioamidethiophenes . Serendipitously, our method enables the one-pot conversion of various alkyne-appended β-ketonitriles into thieno­[2,3- c ]­isothiazoles in the presence of LR (vide infra).…”