Highly efficient synthesis of pyrazolylphosphonate derivatives in biocompatible deep eutectic solvent

Abstract A straightforward and highly efficient one-pot preparation of biologically interesting pyrazolylphosphonate derivatives via a three-component reaction between pyrazolone or phenylpyrazolone, various aromatic, fused aromatic, heterocyclic, and aliphatic aldehydes, and triethyl or trimethyl phosphite in presence of an ammonium-based deep eutectic solvent (DES) at 25 °C has been developed. The ammonium-based DES was easily prepared from choline chloride and urea (1:2) at 80 °C for 2 h. It is biodegradable, fairly inexpensive, easily separated from the reaction mixture using water, and can be reused at least four times without loss of its catalytic activity. The most important features of this method are its eco-friendliness, high yields, high atom economy, and the fact that it does not require column chromatographic purification for isolation of the products. Thus, it represents an alternative method for the synthesis of a wide range of pyrazolylphosphonates with shorter reaction times.