Synthesis of 3- and 5-formyl-4-phenyl-1H-pyrazoles: promising head units for the generation of asymmetric imineligands and mixed metal polynuclear complexes

Abstract

Two synthetic methodologies are reported for the generation of 4-phenyl-1H-pyrazoles substituted at the 3- and/or 5-positions. Functionalisation of the 4-position of dimethyl-4-iodo-1-(tetrahydropyran-2-yl)-3,5-pyrazolecarboxylate (10) to produce dimethyl-4-phenyl-1-(tetrahydropyran-2-yl)-3,5-pyrazolecarboxylate (14) was achieved by a C–C Suzuki–Miyaura cross coupling reaction in water. However, low yields for this reaction led us to develop a second methodology wherein functionalisation of N-(tetrahydropyran-2-yl)-4-phenylpyrazole (18), synthesised from inexpensive phenylacetic acid, with formyl or hydroxymethyl groups was achieved by lithiation methods. The resulting monoaldehydes, 4-phenyl-5-pyrazole carbaldehyde (20) and 5-formyl-3-(2′-tetrahydropyranyloxymethyl)-4-phenyl-1-(tetrahydropyran-2-yl)pyrazole (28), should facilitate access to new, asymmetric, imine ligands based on a 4-phenyl-1H-pyrazole moiety. This was proven by the successful synthesis of the heterometallic tetranuclear complex [Fe^II(Ni^IIL²)₃](BF₄)₂·solvents. Likewise, the alcohol isolated en route to 28, N-(tetrahydropyran-2-yl)-5-(hydroxymethyl)-4-phenylpyrazole (24), should facilitate access to new, asymmetric, amine ligands.