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Halogen-bonding Catalysis

By George Neuhaus

Abstract

Catalysis plays an important role in all fields of chemistry. Many catalysts used today are heavy metals, which are avoided in pharmaceutical production due to their toxicity. This limits the variety of drugs produced because some reactions are successful only in the presence of these metals. The purpose of this research is to synthesize and test novel halogen-bonding organocatalysts that will improve pharmaceutical synthesis by opening reaction pathways that are currently only available with heavy metals. The catalysts developed will improve catalysis of Michael-type additions by which Paroxetine, an anti depressant, ZemplerⓇ, which prevents kidney disease, and (+)-tanikolide, a potential anticancer drug, are all synthesized.[1] By forming non-covalent halogen-bonds with Lewis basic species, these catalysts will lower transition state energies, which will accelerate the chemical reactions. This project develops two-halogenated imidazolium groups as halogen-bond donors placed on a terphenyl scaffold that allows the correct geometry to bind with carbonyl functionality. The binding strengths of the scaffolds were obtained by NMR titrations. Future studies will include screening Michael-type addition reactions with and without the catalysts to compare the rate of reaction. As a control, a hydrogen-bonding thiourea compound, which has proven to catalyze these types of reactions, will also be screened. This project develops a new genre of organocatalyst and promises to improve pharmaceutical production by optimizing yields, minimizing waste, and opening new pathways to a greater diversity of drugs.

[1] Maltsev, O. V., Beletskaya, I. P., Zlotin, S. G., 2011. Organocatalytic Michael and Friedel-Crafts reactions in enantioselective synthesis of biologically active compunds. Rus. Chem. Rev. 80, 1067-1113.

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Apr 11th, 4:20 PM Apr 11th, 4:40 PM

Halogen-bonding Cataylsis

Halogen-bonding Catalysis

By George Neuhaus

Abstract

Catalysis plays an important role in all fields of chemistry. Many catalysts used today are heavy metals, which are avoided in pharmaceutical production due to their toxicity. This limits the variety of drugs produced because some reactions are successful only in the presence of these metals. The purpose of this research is to synthesize and test novel halogen-bonding organocatalysts that will improve pharmaceutical synthesis by opening reaction pathways that are currently only available with heavy metals. The catalysts developed will improve catalysis of Michael-type additions by which Paroxetine, an anti depressant, ZemplerⓇ, which prevents kidney disease, and (+)-tanikolide, a potential anticancer drug, are all synthesized.[1] By forming non-covalent halogen-bonds with Lewis basic species, these catalysts will lower transition state energies, which will accelerate the chemical reactions. This project develops two-halogenated imidazolium groups as halogen-bond donors placed on a terphenyl scaffold that allows the correct geometry to bind with carbonyl functionality. The binding strengths of the scaffolds were obtained by NMR titrations. Future studies will include screening Michael-type addition reactions with and without the catalysts to compare the rate of reaction. As a control, a hydrogen-bonding thiourea compound, which has proven to catalyze these types of reactions, will also be screened. This project develops a new genre of organocatalyst and promises to improve pharmaceutical production by optimizing yields, minimizing waste, and opening new pathways to a greater diversity of drugs.

[1] Maltsev, O. V., Beletskaya, I. P., Zlotin, S. G., 2011. Organocatalytic Michael and Friedel-Crafts reactions in enantioselective synthesis of biologically active compunds. Rus. Chem. Rev. 80, 1067-1113.