Synthesis and characterization of two bifunctional pyrazole-phosphonic acid ligands

The bifunctional compounds 3,5-dimethyl-4-(4-phosphonophenyl)-1H-pyrazole 1 and 4-(4-phosphonophenyl)-1H-pyrazole 2 were synthesized via Suzuki-Miyaura coupling, starting from a Boc-protected pyrazolylboronic acid ester and the iodoarylphosphonate. The target compounds were isolated after acidic hydrolysis in the form of the hydrochloride salts 1 · HCl and 2 · HCl · H2O with a yield of 81% and 86%, respectively. Pd(dppf)Cl2 was found to be superior to Pd(PPh3)4 as a catalyst; dry 1,4-dioxane as a solvent, Cs2CO3 as a base, and no co-ligands were the best found conditions. The alternative routes through iodoarylphosphonate of iodoarylpyrazole, with the crucial steps based on the copper-catalyzed coupling with acetylacetone or the Arbuzov reaction were proven inefficient. The structures of the isolated hydrochloride salts 1 · HCl and 2 · HCl · H2O feature hydrogen-bonded networks involving the chloride anions.