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

• Hydrazine promotes ANRORC reaction in 2-(trifluoromethyl)-2H-chromen-5(6H)-ones.
• New series of 2-[(1H-pyrazol-4-yl)arylmethyl]-cyclohex-2-en-1-ones is synthesized.
• The respective ANRORC reaction type mechanism is presented and discussed.
• Structures solved by MS, X-ray, DFT calculations and 1H, 13C and 19F NMR data.
• 19F NMR assignments the trifluoromethyl group position at pyrazolyl-cyclohexenones.

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-OCH3C6H4, 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.

A new series of 5(3)-(trifluoromethyl)-1H-pyrazol-4-yl)arylmethyl]-cyclohex-2-en-1-ones from an ANRORC ring transformation reaction of 2-(trifluoromethyl)-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones, in the presence of hydrazine hydrate, at 63–90% yields, is described.Figure optionsDownload as PowerPoint slide