ANRORC rearrangement in tetrahydro-2H-chromenones. Synthesis and structural assignment by NMR, MS, X-ray and DFT calculations of 2-[3(5)-trifluoromethyl- 1H-pyrazol-4-yl)arylmethyl]cyclohexenones and derivatives

Article abstract of DOI:10.1016/j.jfluchem.2013.03.014

This paper describes firstly the synthesis of a new series of 3-hydroxy-2-[(3(5)-(methyl/phenyl)-5(3)-(trifluoromethyl)-1H-pyrazol-4-yl) arylmethyl]-cyclohex-2-en-1-ones (2), where aryl = C₆H₅, 4-NO₂C₆H₄, 4-OCH₃C₆H ₄, from an ANRORC ring transformation reaction of 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H) -ones (1), where acyl = acetyl and benzoyl, in the presence of hydrazine hydrate, at 63-90% yields. In subsequent steps, an oxidative aromatization reaction from 2 was done in an iodine/methanol medium for the preparation of 3(5)-trifluoromethyl-5(3)-methyl-4-[(2,6-dimethoxyphenyl)-(4- methoxyphenylmethyl)]-1H-pyrazole (3) at 72% yields. Also, the alkylation reaction using benzyl chloride easily converted a pyrazole like 2 to its N-benzyl derivative (4), at 69% yield. Finally, the structural assignment of compounds 2-4 was deduced by mass spectrometry, X-ray crystal diffraction and density functional theory (DFT) calculations, which clearly and unambiguously furnished values very close to those determined from ¹H, ¹³C and ¹⁹F NMR data.