title: Oxidative ring expansion of spirocyclic oxindole derivatives.
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.
authors.affiliation: Unit of Organic Chemistry, Department of Biosciences at Novum, Karolinska Institute , SE-14157 Huddinge, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Bergman
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Arewång
authors.forename: Per H
authors.initials: PH
authors.lastname: Svensson
mesh_terms: D018360:Crystallography, X-Ray; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D007510:Isatin / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D000078183:Oxindoles; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D062367:ortho-Aminobenzoates / Q000737:chemistry*
chemical_list: D007211:Indoles; D000078183:Oxindoles; D011799:Quinazolines; D052999:Quinazolinones; D013141:Spiro Compounds; D062367:ortho-Aminobenzoates; C000598090:quinazolino(4,5-b)quinazoline-6,8-dione; C000598089:spiro(3H-indole-3,2'(1H)quinazoline)-2,4'(1H,3H)dione; C022960:2-oxindole; D007510:Isatin; C000219:anthranilamide