CINOXACIN synthesis

Cinoxacin, 1-ethyl-1,4-dihydro-4-oxo[1,3]-dioxolo[4,5-g] cinnolin-3-carboxylic acid (33.2.14), is synthesized by a different scheme starting with 2-amino-4,5-methylendioxyacetophenone (33.2.10), which is synthesized by reducing 4,5-methylendioxy-2-nitroacetophenone with hydrogen over a platinum catalyst. In diazotation conditions, this undergoes spontaneous heterocyclization to 4-hydroxy-6, 7-methylendioxycinnoline (33.2.11) obviously due to the presence of a significant amount of the enol form of acetophenone (33.2.10) under the reaction conditions. The resulting cinnoline (33.2.11) then undergoes bromination by molecular bromine in the presence of potassium acetate, giving 3-bromo-4-hydroxy-6,7-methylendioxycinnoline (32.2.12). Upon reacting this with univalent copper cyanide in dimethylformamide, the bromine atom is replaced with a cyano group, forming the 3-cyano-4-hydroxy-6,7-methylendioxycinnoline (33.2.13). The resulting product is alkylated at the first position by ethyl iodide using sodium hydride as a base, and the cyano group is hydrolyzed to a carboxyl group using a mixture of hydrochloric and acetic acids, giving the desired cinoxacin.