An eco-efficient pilot plant scale synthesis of two 5-substituted-6,7-dimethoxy-1-H-quinazoline-2,4-diones

Abstract

Two 1-H-quinazoline-2,4-diones having substituents at the 5-position have been prepared on a pilot-plant scale using an eco-efficient process. The process started with the appropriately substituted ortho-nitrobenzoic acid and involved a catalytic hydrogenation, conversion of the generated aniline to a substituted urea, cyclization and precipitation of the desired 1-H-quinazoline-2,4-diones. The process is unique in that all stages of the process were conducted in water. The desired transformations were affected by manipulation of the pH of the reaction mixture, and addition of the necessary reagent. The products were isolated in near-quantitative yield and were analytically pure. The only waste streams were the aqueous filtrate and the noble metal catalyst. The process was demonstrated on scales up to 5 kg.