Palladium-Catalyzed and Microwave-Assisted Suzuki-Miyaura Cross-Coupling to Access Carbazole Intermediate Using Cyrene^TM as a Neoteric Bio-Based Solvent

Abstract:

The development of drug lead compounds has been a focus in organic synthesis methods due to their emerging potential in biomedical applications. However, most synthesis methods involve the use of hazardous solvents, which contribute negatively to the environment with continued use, leading to regulations that limit the use of these solvents. Hence, this study was done to assess the feasibility of Cyrene^TM, a neoteric bio-based green solvent, as an alternative to industrial, dipolar aprotic organic solvents such as DMF and DMSO. The methodology for this study consists of several steps, including preparation of materials, microwave synthesis, thin-layer chromatography, extraction of the products formed, purification and isolation of the target compound, and finally, data analysis. The reaction of interest is the carbazole intermediate formation through Suzuki-Miyaura cross-coupling between 2-iodoaniline and 2-bromophenylboronic acid in Cyrene^TM in the presence of Pd (OAc)₂ and PPh₃ as the catalyst and ligand under microwave-assisted conditions. Through NMR spectroscopy, the isolated product was identified to be 2’-bromobiphenyl-2-amine, with functional groups verified through FTIR spectroscopy. Optimal conditions in Cyrene^TM involve using Cs₂CO₃ as the base at 90 °C for 2 hrs. However, side reactions in Cyrene^TM resulted in lower yields in comparison to DMSO at 130 °C. It is recommended to identify new methods to minimize the Cyrene^TM side reactions that adversely affect product yield and to test the possibility of completing the carbazole formation via cascade C-C/C-N bond formation under microwave irradiation with Cyrene^TM as a solvent.

• Periodical: Materials Science Forum (Volume 1194)
• Pages: 141-147
• DOI: https://doi.org/10.4028/p-bY4KyO
• Online since: June 2026
• Authors: Jose Gabriel H. Escorial, Jared Christian N. Español, Erika Mae V. Naquila, Ramuel John I. Tamargo*
• Keywords: Carbazole, Cyrene, Green Solvents, Microwave-Assisted Synthesis, Suzuki-Miyaura Coupling

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