Synthesis of 2-Methylquinazolinones Through Skeleton Editing Strategy Using Calcium Carbide as an Inorganic C2 Source.

Abstract

A skeleton editing strategy for the construction of 2-methylquinazolin-4(3H)-ones is described. This transformation employs commercially available benzo[c]isoxazoles as the skeleton framework, calcium carbide as an inorganic C2 source, and sulfonyl azides as nitrogen sources. The reaction proceeds via a cascade of [3 + 2] cycloaddition, oxidative addition, reductive elimination, nucleophilic addition, and dehydrogenation. A broad range of substituted benzo[c]isoxazoles and sulfonyl azides were tolerated under the optimized conditions, affording the desired products in good to high yield. The protocol is amenable to gram-scale synthesis and features the use of an inexpensive, easy-to-handle solid C2 source in place of flammable and explosive gaseous acetylene, together with a low-cost catalyst, mild conditions, satisfactory yields, and straightforward workup procedures.