Green synthesis: The use of brown algae in the synthesis of palladium nanoparticles and their application as catalysts in the synthesis of important pharmaceutical intermediates

Abstract

Environmental awareness and concern have led to the development of green chemistry protocols which aim to mitigate the negative impact of the pharmaceutical industry on the environment. The biaryl ring system is common to a number of active pharmaceutical ingredients (APIs). The aim of the current study is to utilize waste biomass generated during the isolation of seaweed natural products to synthesise “green” palladium nanoparticles (PdNPs) that will be used to catalyze biaryl coupling reactions.

Green chemistry is defined as the design of chemical processes and products that reduce or eliminate the generation and use of hazardous substances. This protocol is guided by a set of rules, commonly known as the 12 principles of green chemistry. Many synthetic methods that were used before the development of this protocol made use of toxic reagents and solvents that were harmful or detrimental to the environment. Green chemistry, therefore, makes use of less harmful substances, such as plants, seaweeds, and green reagents and/or solvents. This study will further explain the use of Sargassum incisifolium, a species of brown algae found on the west coast of Southern Africa to synthesize palladium nanoparticles. Two types of extracts- an aqueous extract (AE) and an organic aqueous extract (OAE) were prepared from the seaweed. Before any further use, the extracts were characterized by NMR and UV- Visible spectroscopy, and their polyphenolic content, reducing capacity, and radical scavenging ability was determined. Further characterization of the extracts was carried out by FTIR and TGA analyses.

The PdNPs were successfully synthesized and characterized by UV-Visible spectroscopy, TGA, TEM, XRD, FTIR, and ICP-OES. Following characterization, the PdNPs were used to catalyze Suzuki-Miyaura carbon- carbon coupling reactions. The TEM results revealed that the AE-PdNPs have an average size of 8.5 nm, while the OAE-PdNPs are 10.5 nm in size. The disappearance of the SPR band at 415 nm in the UV-visible spectra indicated that the Pd(II) in the palladium salt was successfully reduced to Pd(0) by the polyphenols present in the extracts. The XRD data proved that the nanoparticles were crystalline in nature. The OAE PdNPs revealed well-defined diffraction peaks at 2Ɵ 29.3o, 41.2o , 47.4o , 51.3o , and 59.5o which can be indexed to reflections from the (002), (111), (200), (200), and (220) planes of fcc crystal structure of metallic palladium.

The catalytic ability of the nanoparticles was then assessed in a model Suzuki-Miyaura coupling reaction using phenylboronic acid and 4-iodoanisole as the starting materials and DMF:H2O (95:5) as the solvent, in the presence of potassium carbonate as the base. This reaction was successfully repeated with different greener solvents, such as ethanol and acetone, and the recyclability of the catalyst was also studied. Cyrene was also employed as a greener solvent; however, this reaction was unsuccessful. Another Suzuki-Miyaura coupling reaction was carried out for the synthesis of 4-bromomethyl-2- biphenyl carbonitrile- an important intermediate of the API losartan. All of the products of the coupling reactions were analyzed by NMR, UV-Visible spectroscopy, FTIR, and HPLC. The HPLC results revealed that both the PdNPs and Pd/C catalysts were recyclable up to 10 cycles and the coupling reactions were successful, with yields of >90% when EtOH:H2O was used as the solvent; and when Acetone:H2O was used as the solvent, the yields dropped to ~70%. It was further revealed that, although the coupling occurred, the products that were formed from these coupling reactions were not the desired products, but may easily be converted into the desired intermediate.

The reactions mentioned above have proven that waste biomass generated in the isolation of seaweed natural products were successfully used in the green synthesis of PdNPs. The latter successfully catalyzed biaryl formation via the Suzuki-Miyaura reaction.