Synthesis of Tetravalent Boron Complexes with Pyrazolone-Based Ligand and their Drug-Likeness

Abstract

Boron chemistry is one of the most interesting fields for synthetic organic chemists. In present investigation we synthesized 3-methyl-1-phenyl-2-pyrazolone from the reaction of ethyl acetoacetate and phenyl hydrazine. 3-methyl-1-phenyl-2-pyrazolone treated with benzene diazonium chloride to furnish arylazo pyrazolone ligand. Boric acid reacts with isopropanol in benzene to form boron isopropoxide as a colourless viscous liquid. Refluxing of boron isopropoxide with catechol in benzene gives isopropoxy-benzodioxaboron. isopropoxy-benzodioxaboron and 3-methyl-1-phenyl-2-pyrazolone was refluxed in benzene to give four coordinated boron complexes. The structures of all synthesized compounds were confirmed by physical and analytical data. All synthesized arylazo pyrazolone ligand were evaluated for drug-likeness under Lipinski’s, Ghose, Veber, Egan and Muegge’s rules and may have good drug candidature.

Introduction

Boron is a biologically and chemically important element due to its electrophilic nature and ability to coordinate with nucleophiles such as hydroxyl and amino groups. Tetra-coordinated boron complexes exhibit diverse biological activities—including antibacterial, antifungal, antitumor, antioxidant, and enzyme inhibition—and are widely studied for their unique coordination chemistry and Lewis acidity, with applications in catalysis.

In this work, pyrazolone ligands (HPAP-1 to HPAP-6) were synthesized and then complexed with 2-isopropoxy-1,3,2-benzodioxaborole to form tetracoordinated boron complexes. The reactions were monitored using IR, ¹H-NMR, and ¹¹B-NMR spectroscopy, confirming N,O-coordination and the formation of stable complexes. Physical characterization showed good yields, defined melting points, and consistent elemental analysis.

Additionally, physicochemical and drug-likeness properties of the ligands were predicted in silico using SwissADME. Molecular weight, lipophilicity, hydrogen-bonding features, and polar surface area indicate that these compounds satisfy multiple oral drug-likeness rules (Lipinski, Ghose, Veber, Egan, Muegge), suggesting potential as biologically active agents.

Conclusion

The present study reports the successful synthesis of a series of tetra-coordinated Boron complexes derived from the reaction of 2-isopropoxy-1,3,2-benzodioxaborole with 5-methyl-2-phenyl-4-(2-phenylhydrazinylidene)-2,4-dihydro-3H-pyrazol-3-one ligands. The formation of these complexes is facilitated by the strong electron-withdrawing nature of the catecholate dianion, which enhances the Lewis acidity of the boron center and promotes coordination with the azo-pyrazolone ligand. Furthermore, the evaluation of physicochemical properties revealed that the synthesized compounds possess molecular weights, lipophilicity, hydrogen bonding capacity, and polar surface area within the acceptable limits for drug-like molecules. According to Lipinski’s rule of five and other drug-likeness filters, the compounds exhibit favourable characteristics for potential oral bioavailability. Overall, the study demonstrates that the synthesized boron complexes show promising structural and physicochemical properties, suggesting their potential as candidates for further investigation in medicinal and pharmaceutical applications.

References

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Copyright © 2026 Suman Khinchi, Ashok Kumar Patidar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.