1-Bis(methoxy)-4-bis(methylthio)-3-buten-2-one: useful three carbon synthon for synthesis of five and six membered heterocycles with masked (or unmasked) aldehyde functionality

Abstract

1-Bis(methoxy)-4-bis(methylthio)-3-buten-2-one has been shown to be a useful three carbon synthon for efficient regiospecific synthesis of a variety of five (pyrazole and isoxazole) and six membered (pyrimidines, pyridone and pyridines) heterocycles with masked (or unmasked) aldehyde functionality by cyclocondensation with bifunctional heteronucleophiles such as hydrazine, hydroxylamine, guanidine, thiourea, cyanoacetamide and substituted β-lithioaminoacrylonitriles. Reaction of 1-bis(methoxy)-4-bis(methylthio)-3-buten-2-one with methylene iodide and Zn-Cu couple under Simmons-Smith reaction conditions afforded 2-(methylthio)thiophene-4-aldehyde in good yield, whereas cycloaromatization with thiophene-2- and 3-acetonitriles gave the corresponding substituted benzothiophene-4- and 7-aldehydes in good yields.