A Novel Synthesis of 2-Aryl-4-quinolones from 2-Aminobenzoic Acids

2-Aryl-4-quinolones, aza analogs of flavones, have played a central role in medicinal chemistry because they possess potent antimitotic antitumor effects through inhibition of tublin polymerization at the colchicine site. 1 The general method for preparing 2-aryl-4-quinolones is a condensation of anilines with ethyl benzoylacetates, 2 thioalkylidene-1,3dioxane-4,6-diones, 3 and diethyl 2-(ethoxymethylene)malonate 4 in diphenyl ether at 240-250 o C. This process is amenable for scale-up and the starting material anilines are widely available, but it can lead to regioisomers depending on the structure of anilines. The cyclization of N-(2-acetylphenyl)benzamides, which are prepared from the benzoylation of 2'-aminoacetophenones with benzoyl chlorides 5 or Friedel-Crafts acylation of N-phenylbenzamides with acetyl chloride, 6 with potassium t-butoxide gives 2-aryl-4-quino