Isamic acid

Isatin (190) is a compound with interesting chemistry. It can be iV-acetylated with acetic anhydride, iV-methylated via its sodium or potassium salt and O-methylated via its silver salt. Oxidation of isatins with hydrogen peroxide in methanolic sodium methoxide yields methyl anthranilates (81AG(E)882>. In moist air, O-methylisatin (191) forms methylisatoid (192). Isatin forms normal carbonyl derivatives (193) with ketonic reagents such as hydroxylamine and phenylhydrazine and the reactive 3-carbonyl group also undergoes aldol condensation with active methylene compounds. Isatin forms a complex derivative, isamic acid (194), with ammonia (76JCS(P1)2004). 

The structure of isamic acid, CieH11N303 H20, obtained from ammonia and isatin or from sodium isatoate and 151 (R = H) has been studied for some time.445,446 In 1967 structure 156 was suggested for... 

Isatin reacts with ammonium hydroxide or ammonium acetate to furnish a mixture of compounds. Amongst them are isamic acid and its corresponding amide, isamide. Since 1877 there had been a discussion as to their structure, which in 1976 was finally elucidated, by Sir John Comforth on the basis of chemical and spectroscopic data228. Isamic acid can be regarded as a dimer formed by the addition/condensation of one equivalent of ammonia with two equivalents of isatin. This intermediate suffers lactonization and subsequent conversion to isamic acid by an internal nucleophilic attack, where upon the acid is converted to isamide by reaction with a second equivalent of ammonia. 1-Methylisatin reacts similarly, furnishing N-methylisamic acid (Scheme 51). 

The isamate and isamide, by the action of acids, produce either isamic acid or isatine. . . id. chloro. 

The red crystalline product, called isamic acid, from treatment of isatin with ammonia, was proved by Cornforth to be the spiro-1,2-dihydroquinazoline-4-carboxylic acid 66 (R = H). iV-Methylisatin provided the dimethyl derivative (66 R = Me). Isamic acid has an asymmetric carbon atom and is chiral. In an attempted optical resolution, its brucine salt gave... 

Isamic acid from angokea oil has been used as a drying oil. " ... 

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