Domino Synthesis of Thiazolo-Fused Six- and Seven-Membered Nitrogen Heterocycles via Intramolecular Heteroannulation of In-Situ-Generated 2‑(Het)aryl-4-amino-5-functionalized Thiazoles

• Published in: Journal of organic chemistry 2022-09, Vol.87 (18), p.12397-12413
• Main Authors: Kumar, Yogendra, Ila, Hiriyakkanavar
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c01673

Synthesis of novel 2-(het)­aryl-substituted thiazolo-fused six- and seven-membered heterocycles, such as thiazolo­[4,5-b]­pyridin-5­(4H)-ones, thiazolo­[4,5-c]­isoquinolin-5­(4H)-ones, thiazolo­[4,5-b]­quinolin-9­(4H)-ones, 4H-benzo­[e]­thiazolo­[4,5-b]­azepine-5,10-diones, have been developed in a single-pot operation via intramolecular heteroannulation of in-situ-generated 2-(het)­aryl-4-amino-5-functionalized thiazoles. These 4-amino-5-functionalized thiazoles were readily obtained in a one-pot process by treatment of a range of (het)­aryldithioesters with cyanamide in the presence of NaH, followed by in situ S-alkylation-intramolecular condensations of the resulting thioimidate salts with appropriate activated methylene halides. On the other hand, the corresponding 4H-benzo­[b]­thiazolo­[4,5-e]­[1,4]­diazepin-10­(9H)-ones were synthesized in a two-step process, requiring prior isolation of 5-carboethoxy-4-(2-nitrophenyl)­aminothiazoles and their subsequent reductive cyclization. The activated methylene halides employed in these reactions for the synthesis of various thiazolo-fused heterocycles were methyl bromocrotonate, ethyl 2-(bromomethyl)­benzoate, 2-fluorophenacyl bromides, ethyl 2-(2-bromoacetyl)­benzoate, and ethyl bromoacetate. Several of these thiazolo-fused heterocycles display yellow green to green fluorescence, and their absorption and emission spectra have also been examined.