Application of organolithium and related reagents in synthesis; Part 26. Synthetic strategies based on directed ortho- metalation: Synthesis of 4-methyl-2H-phthalazin-1-ones

The synthesis of 3-hydroxy-3-methylisoindolin-1-ones 10, masked ortho-acety lated derivatives of anilides, via metalation (BuLi) of the benzanilides 1 and subsequent reaction of the generated bis-lithiated anilides 2 with acet ylating agents such as acetic anhydride or ethyl acetate were studied. The 3-hydroxy-3-methylisoindolin-1-ones 10 thus obtained are very sensitive tow ards dehydration process, which caused their conversion into enamides 11. C onversion of 3-hydroxy-3-methylisoindolin-1-ones 10 or enamides 11 into the corresponding 4-methyl-2H-phthalazin-1-ones 13 by treatment with hydrazine , as a way of regioselctive transformation of the benzoic acids, is also de scribed.