NEIGHBORING CARBOXY-GROUP CATALYSIS OF RING-OPENING OF 3,1-BENZOXAZIN-4-ONES

Efficient intramolecular catalysis of the hydrolysis of 2-methyl-3,1 -benzoxazin-4-ones to N-acetylanthranilic acids by a neighbouring carboxy-group [as in (6)] is demonstrated. The 8-carboxy-compound (6) reacts 250-fold faster than the 6-carboxy-isomer (7) at pH 6. A mechanism involving the 8-carboxy-group as an internal general acid catalyst is proposed. The 5-carboxy-isomer (9) does not show enhanced reactivity but, consistent with attack of the nucleophile at the 4-position of the benzoxazinone, hydroxide ion catalysed hydrolysis is actually depressed by the presence of the CO2 - group in this position. The anhydride (13) (formed by reaction of 3-aminophthalic acid with acetic anhydride) is hydrolysed directly (by H2O or HO - attack) at pH < 10; however at pH > 10 a preliminary rearrangement of the anhydride (13) to the benzoxazine (9) occurs.