Isatoic anhydride conversion

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

Isatoic anhydride undergoes a one-step conversion to o-aminophenyloxazolines 2 with amino alcohols via elimination of carbon dioxide. The reaction is carried out in the presence of kaolinitic clay in refluxing chlorobenzene. These o-aminophenyloxazolines, in particular, those derived from chiral amino alcohols,... 

There are two important general types of reaction by which six-membered heterocycles containing two or more heteroatoms can be transformed into other six-membered heterocyclic systems, namely reactions which involve an ANRORC mechanism, and reactions which proceed by a Diels-Alder/retro-Diels-Alder type of mechanism. Transformation of 1,3-oxazinones and -thiazinones into pyrimidones (equations 193 and 194) has been extensively used, especially in the conversion of isatoic anhydride into quinazolinones (e.g. equation 195). 2,4-Diaryl-l,2,3,5-oxathiadiazines, which are readily accessible by reaction of sulfur trioxide with aryl isocyanates, are useful precursors to pyrimidines and 1,3,5-triazines (equation 196). 

A study of all the stages in the synthesis of 4-aminoquinazolines from isatoic anhydride, via anthranilamide and o-aminobenzonitrile, made possible the preparation of these compounds by a one-pot synthesis. The anhydride was treated with ammonia in dimethylformamide, nitrogen was then bubbled through the solution to remove excess of ammonia, phosphoryl chloride was added and heated at 40°-60°C for conversion into the nitrile, and finally the respective amine was added to yield the 4-(substituted-amino)-quinazolines in 44-79% yields. ... 

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