Regioselective synthesis and through-space 13C–19F spin–spin coupling NMR of new tetracyclic 3-(trifluoromethyl)-spiro(chromen[4,3-c]pyrazole-4,1′-cycloalkanes)

• Published in: Journal of fluorine chemistry Vol. 166; pp. 44 - 51
• Main Authors: Bonacorso, Helio G., Garcia, Fábio D., Belo, Chaiene R., Tier, Aniele Z., Frizzo, Clarissa P., Martins, Marcos A.P., Zanatta, Nilo
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-10-2014
• Subjects: Benzopyrans; Cycloalkanes; Kabbe adducts; Pyrazoles; Spiroketones; Benzopyrans; Spiroketones; Cycloalkanes; Pyrazoles; Kabbe adducts
• ISSN: 0022-1139; 1873-3328
• DOI: 10.1016/j.jfluchem.2014.07.011

The regioselective synthesis and through-space 13C–19F spin–spin coupling NMR of a new series of seven spiro-condensed 1(2)-methyl(phenyl)-3-(trifluoromethyl)-1,4(2,4)-dihydro-spiro(chromen-[4,3-c]pyrazole-4,n′-cycloalkanes), at 35–51% yields, is reported.
•TFAA in the acylation of spiro[chroman-2,1′-cycloalkan]-4-ones (Kabbe's adducts).•3-(Trifluoromethyl)-spirochromen[4,3-c]pyrazole-4,1′-cycloalkanes are synthesized.•Through-space 13C–19F spin–spin coupling NMR is presented and discussed.•Structures solved by 1H, 13C and 19F NMR (spin–spin coupling), MS and X-ray data.•19F NMR assigned the trifluoromethyl group position at pyrazole derivatives.
This paper firstly describes an efficient and regioselective method for the synthesis of a new series of 2,2,2-trifluoro-1-[4-methoxy-spiro(2H-chromen-2,1′-cycloalkane)-3-yl]ethanones from spiro[chroman-2,1′-cycloalkan]-4-ones (Kabbe's adduct). Yields of 38–61% were obtained when trifluoroacetylation reactions of mixtures of enolethers and/or acetals derived from four spiro ketones (Kabbe's adduct) were performed at a temperature of 45°C, employing anhydrous chloroform as the solvent. Subsequently, when the respective trifluoroacetylated Kabbe adducts reacted with phenylhydrazine and methylhydrazine at a 1:1 molar ratio in refluxing ethanol for 24h, a new series of seven examples of a new spiro-condensed heterocyclic system, namely 1(2)-methyl(phenyl)-3-(trifluoromethyl)-1,4(2,4)-dihydro-spiro(chromen[4,3-c]pyrazole-4,n′-cycloalkanes) – where cycloalkanes are cyclopentane, cyclohexane, and cycloheptane for n=1; and tetrahydro-2H-pyran for n=2 – were isolated at yields of between 35% and 51%. Finally, the structures of new spiro heterocycles were determined with the aid and simultaneous application of 1H, 13C and 19F one-dimensional and gHMBC NMR experiments, X-ray monocrystal diffraction, and mass spectrometry techniques.