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.

Synthesis of novel 2-(het)aryl-substituted thiazolo-fused six- and seven-membered heterocycles, such as thiazolo[4,5-]pyridin-5(4)-ones, thiazolo[4,5-]isoquinolin-5(4)-ones, thiazolo[4,5-]quinolin-9(4)-ones, 4-benzo[]thiazolo[4,5-]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 -alkylation-intramolecular condensations of the resulting thioimidate salts with appropriate activated methylene halides. On the other hand, the corresponding 4-benzo[]thiazolo[4,5-][1,4]diazepin-10(9)-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.