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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Oxidative ring expansion of spirocyclic oxindole derivatives
Jan Bergman1, Carl-Johan Arewång, Per H Svensson
1Unit of Organic Chemistry, Department of Biosciences at Novum, Karolinska Institute , SE-14157 Huddinge, Sweden.
Abstract:
Oxidation of the spirocyclic oxindole derivative, isamic acid 1, led to decarboxylation and ring expansion to quinazolino[4,5-b]quinazoline-6,8-dione 7 rather than, as previously believed, its isomer 6. The structure of 7 was confirmed by X-ray crystallography. Condensation of isatin (indole-2,3-dione) and 2-aminobenzamide led to the spirocyclic molecule, spiro[3H-indole-3,2'(1H)quinazoline]-2,4'(1H,3H)dione 8, which was also identified as an intermediate in the oxidation of isamic acid. Mild hydrolysis of 7 gave the 10-membered molecule 22. Isamic acid could easily be converted to N-nitrosoisamic acid, which when heated in ethanol underwent a ring expansion to a hydroximino derivative, 38, of compound 6. The structure of 38 was confirmed by X-ray crystallography.
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