Difunctional Pyrazole Derivatives − Key Compounds en Route to Multidentate Pyrazolate Ligands

Abstract

Straightforward syntheses for some basic functional pyrazole derivatives are reported. These compounds serve as starting materials for the preparation of a series of new 3,5-donor-substituted multifunctional pyrazole compounds, which may act as compartmental dinucleating ligand scaffolds for the controlled assembly of bimetallic complexes. The thp-protected 3,5-bis(chloromethyl)pyrazole (1), and in particular the more reactive 3,5-bis(bromomethyl) analogue 3, permit efficient attachment of various N-donor side arms through nucleophilic substitution reactions. The preparation of the enantiomerically pure (methoxymethyl)pyrrolidine derivative 2e by this route makes use of the intrinsic C2 symmetry of the pyrazole-based framework, and a dizinc complex 2e·(ZnCl2)2 has been characterized crystallographically. The thp-protected pyrazoledicarbaldehyde 6 affords access to pyrazole derivatives bearing aldimine donor side arms, which may be viewed as coupled dinucleating versions of α-diimine ligands. DIBAH reduction of thp-protected dimethyl 1H-pyrazole-3,5-dicarboxylate 4 yields the unsymmetrically functionalized methyl 3-hydroxymethyl-1H-pyrazole-5-carboxylate 8, which has been analyzed by X-ray crystallography. Compound 8 is shown to provide a route to unsymmetrical pyrazole ligands with different chelating side arms in the heterocycle 3- and 5-positions, such as the thioether/amine system 11.