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Please login or sign up for a free trial to access the full content. Synthesis from 2-Bromobenzamides and α-Amino Acids

DOI: 10.1055/sos-SD-116-01020

Kang, F.-A.; Yang, S.-M.Science of Synthesis Knowledge Updates, (20152201.

The condensation of 2-bromobenzamides 94 with α-amino acids 95 in the presence of a copper catalyst under aerobic conditions generates 2-substituted quinazolinones 96 in moderate to good yields by Ullmann-type N-arylation, decarboxylation, aerobic oxidation, and intramolecular addition (Scheme 26).[‌23‌] Copper(I) bromide is a superior catalyst to copper(I) iodide, copper(I) chloride, copper(II) oxide, copper(I) oxide, copper(II) chloride, and copper(II) acetate and potassium carbonate is a better base than cesium carbonate, sodium carbonate, and tripotassium phosphate. A small amount of ethylene glycol also boosts the reaction yield. This reaction tolerates various R1 groups and a variety of alkyl and aryl R2 substitutions. Only the Ullmann-type amino acid coupling product is obtained when the reaction is carried out under a nitrogen atmosphere instead of under air (aerobic conditions).

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