Anthranilic acid, ammonium salt

The reaction is accomplished by simply heating together phthalic anhydride and ammonium carbonate. Phthalimide then hydrolyzes with potassium hydroxide yielding the potassium salt of phthalamidic acid and this acid amide compound undergoes the Hofmann reaction (pp. 148, 685) with bromine (or chlorine) and potassium hydroxide by which one of the carboxyl groups is replaced by the amino group yielding amino benzoic acid or anthranilic acid. 

In 1895, Niementowski discovered the reaction that still bears his name the condensation of 2-aminobenzoic acid (anthranilic acid) with formamide to give quinazolin-4-one. He used two molecular equivalents of formamide and heated at 125°C for 3 hr.279 The yield is excellent, even on the 500 g scale.280 The reaction also goes well when the benzene ring is substituted, whether by electron-attracting or electron-releasing substituents.1 The course of the reaction is as follows.281,282 Ammonium-2-formamidobenzoic acid is first formed and can be isolated when the reaction is run at a lower temperature. At 130°C, this salt is dehydrated to 2-formamidobenzamide (163), which slowly cyclizes to quinazolin-4-one. 

Attempts have been made to improve yields by (a) starting with the preformed ammonium salt,283 (b) doubling the proportion of formamide,282 or (c) running the reaction at a low and then a higher temperature.282,284 Seventeen C-substituted anthranilic acids were converted to quinazolin-4-ones by heating at 130°C for 45 min, then at 175°C for 75 min, and the yields were excellent.284... 

In 1905, Bogert and Chambers described the synthesis of 32 via the acetanthranil intermediate 31, which was formed by heating 2-amino-6-nitrobenzoic acid (30) with acetic anhydride." It was reported that the yield for this reaction was nearly quantitative. This modification was compared to other variations known at that time, including heating the ammonium salt of anthranilic acid with formamide and heating the ammonium salt of N-acetylanthranilic acid, and proved to be superior. A 4-quinazolone without a substituent at the 3-position (35) has also been prepared by this method. ... 

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