Oxidative Ring Expansion of Spirocyclic Oxindole Derivatives

• Published in: Journal of organic chemistry 2014-10, Vol.79 (19), p.9065-9073
• Main Authors: Bergman, Jan, Arewång, Carl-Johan, Svensson, Per H
• Format: Article
• Language: English
• Subjects: Crystallography, X-Ray; Indoles - chemical synthesis; Indoles - chemistry; Isatin - chemistry; Medicin och hälsovetenskap; Molecular Structure; ortho-Aminobenzoates - chemistry; Oxidation-Reduction; Quinazolines - chemical synthesis; Quinazolines - chemistry; Quinazolinones - chemical synthesis; Quinazolinones - chemistry; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/jo501269f

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.