Development of Environmentally Benign Sustainable Synthetic Methods for Biologically Active Compounds and Synthetic Building Blocks
Date of Award
Campus Access Dissertation
Doctor of Philosophy (PhD)
The goal of the present work was to develop organic syntheses that comply with the principles of green chemistry, as alternatives to the traditional method that often have a significant environmental impact. Notably, the principle of catalysis was exploited, water was employed as a green solvent, and safe methods were carefully designed. Four projects are described which demonstrate that the environmentally-friendly features of synthetic methods do not necessarily compromise performances. In fact, the eco-friendly methods reported afford high yields and selectivities.
The first project describes a novel environmentally benign approach based on microwave-assisted solid phase diazotization to convert o-phenylenediamines to substituted benzotriazoles, useful in the dye and pharmaceutical industry. The reaction was carried out in solid phase under microwave irradiation, taking advantage of the strong microwave absorption capability of K-10 montmorillonite that acted as a catalyst and medium in one. Excellent yields were obtained for a broad range of phenylenediamines; the catalyst was recyclable, the reaction occured with high efficiency and does not produce any harmful waste.
The second project outlines an efficient and environmentally benign deprotection of a broad range of benzyl (Bn), benzyloxycarbonyl (Cbz) and Allyloxycarbonyl (Alloc) protected amines, alcohols and amino acids with the M-Al-H2O (M=Ni, Pd) system. The reactions were performed in water under mild conditions. The efficient in situ generation of hydrogen from water and Al is utilized by the hydrogenation catalysts (Ni or Pd) thus facilitating the hydrogenolysis of the protecting groups. Good to excellent yields were obtained for the deprotection of a variety of protected amines, alcohols and amino acids demonstrating the versatility and the practicality of the method.
The third project is based on a similar system using D2O in lieu of H2O to introduce deuterium without the need for the explosive deuterium gas. D2 gas was generated in situ while the commercially available palladium catalyst assisted the H-D exchange reaction. The chemo/regioselective H-D exchange of amino acids and synthetic building blocks yielded promising results. The importance of isotope labeled compounds in medicinal chemistry, notably their use as improved drug candidates and biological probes, makes this efficient and selective method of great interest.
Last, the simple and straightforward catalyst-free synthesis of diarylhydrazones is reported. The structure of the newly synthesized molecules resemble the structure of resveratrol, well-known for its antioxidant properties. The presence of nitrogen atoms in the hydrazones are believed to provide better bioavailability than resveratrol making them good candidates for dietary supplement.
Kokel, Anne, "Development of Environmentally Benign Sustainable Synthetic Methods for Biologically Active Compounds and Synthetic Building Blocks" (2019). Graduate Doctoral Dissertations. 518.
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