Research On Synthetic Process Of Halofuginone Coccidiostats 7-Bromo-6-chloro-4 (3H)-quinazolinone

This paper focus on synthesis and industrialization of the intermediate of halofuginone coccidiostats 7-bromo-6-chloro-4 (3H)-quinazolinone:Nitrobenzene as the raw material to prepare 3-bromoanilines by two steps, then 3-bromoaline reacted with chloral hydrate, and the product 3-bromo-isonitrosoacetanilide were cyclized in present of concentrated sulfuric acid, after separation, the product 6-bromo-isatin reacted with sulfuryl chloride to get 6-bromo-5-chloro-isatin. Then the isatin product is oxidized with hydrogen peroxide to form 5-bromo-4-chloro-anthranilic acid. The anthranilic acid were cyclized with formamide to get 7-bromo-6-chloro-4 (3H)-quinazolinone. We simplified the process by omit steam distillation in the preparation of the 3-bromoaniline from nitrobenzene.3-Chlorotoluene were used as the starting material. Through operation of bromination,radical substitution,oxidation by hydrogen peroxide, amination by the cuprous oxide, 2-amino -4-bromide-5-chlorobenzoic acid were obtained, and then cyclized with formamide to form 7-bromo-6-chloro-4 (3H)-quinazolinone. The reaction conditions were explored in detail and screened in some steps, such as bromination, radical substitution, oxidation, which laid the foundation for the industrialization path.Based on the preparation of second route of small scale, the further improvements in large scale were taken, and 7-bromo-6-chloro-4 (3H)-quinazolinone qualified product was obtained successfully.