UC Santa Barbara

ABSTRACT

Applications of Fe Complexes and Nanoparticles as Catalysts in Water

by

Haobo Pang

Given the importance of amine as intermediates for fine chemicals, agrochemicals, pharmaceuticals, dyes and polymers, selective reduction of nitro-containing aromatics and heteroaromatics to the corresponding amines represents an essential methodology. In the previous work of our group, it was found that commercial sources of FeCl3 with only part per million (ppm) levels of Pd, after processing into nanoparticles (NPs), could be used to catalyze reduction of nitroarenes in water at room temperature. Initial research of mine was dedicated to enhancing the activity of such nanoparticle catalysts. In this project, the original Fe/ppm Pd nanoparticles were doped with ppm levels of Ni, which resulted in a significant enhancement of the rates of reductions of nitro-containing aromatics and heteroaromatics in aqueous micellar media at room temperature by three to eight times. A remarkable synergistic effect was uncovered between ppm levels of Pd and Ni embedded within iron nanoparticles. NaBH4 serves as the source of inexpensive hydride. Broad substrate scope is documented, along with several other features including: low catalyst loading (80 ppm Pd and 1600 ppm Ni), low residual metal in the products, and recycling of the catalyst and reaction medium, which together highlight the green nature of this new technology. Such a nanocatalyst was thoroughly characterized by transmission electron microscopy (TEM) and energy-dispersive x-ray (EDX), which showed the content of each element in the nanoparticles. In addition, such synergistic effects were also explained in terms of the structure of the nanoparticles by X-ray absorption spectroscopy (XAS), extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES).

Csp3-Csp3 bond formation significantly extends the available routes for well-known complicated molecular constructions, which undoubtedly has profound implications for preparing pharmaceuticals. Rather than forming Csp3-Csp3 bonds directly, the reductive coupling of a vinyl-substituted aromatic or heteroaromatic and an alkyl bromide or iodide provided an alternate methodology for Csp3-Csp3 bond formation. A commercially available Fe salt was used as catalyst precursor, coordinated by 3,4,7,8-tetramethyl-1,10-phenanthroline. The new C–C bond is regiospecifically formed, at room temperature, at the β-position of the alkene in the presence of Zn as reductant. Such a discovery provided a novel idea for the formation of Csp3-Csp3 carbon bonds in total synthesis. Apart from broad substrate scope (50 samples), including diverse functional groups and heterocycles, this process could be both scaled up and applied to the synthesis of a precursor of a SphK inhibitor, which illustrated the potential application in the pharmaceutical area. Recycling of the reaction medium and an associated low E Factor (< 5) reflect the sustainability of such chemistry. The coupling process was shown to only occur in an aqueous micellar medium, where a radical process is likely, supported by control experiments, deuterium trapping experiments, and radical clock tests. A mechanism based on these data is proposed.

As a third project, novel nanoparticles were developed, derived by reduction of FeCl3 doped with ppm level Pd, for application to Heck couplings in aqueous micellar media. Using nanoparticle catalysis dramatically enhanced the activity of the catalyst, thus the catalytic Pd loading for these couplings was reduced from 2% to 0.1 mol %. It is worth mentioning that such reactions were run between room temperature and 45 °C, which is much lower than the temperature associated with traditional Heck reactions (typically performed at over 100 °C). In addition to broad substrate scope (26 samples), with educts containing various substituents and heterocycles, the process is highlighted by several other key features, including: low residual Pd (Pd = 0 ppm) in the products, recycling of the reaction medium, and low E Factor (<5). These couplings could also be scale up, and two tandem processes in one pot, provided a strong indication for drug manufacturing.

The nanocatalyst was thoroughly characterized by high angle annular dark-field scanning transmission electron microscopy (HAADF-STEM), EDX elemental mapping, and transmission electron cryo-microscopy (cryo-TEM), which revealed the morphology change of the nanocatalyst before and after exposure to water. X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma mass spectrometry (ICP-MS) provided an explanation of such a change in morphology in terms of elemental content. More research of such nanocatalysts is still in process.