RFFI 19-03-01053
«New strategies for synthesis of functionally substituted N-heterocyclic carbenes and their complexes with transition metals»
Modern chemistry and pharmaceuticals are unthinkable without metal complex catalysis. Metal complex catalysis plays a special role in the pharmaceutical industry.
In the production of drugs, it is necessary to change the structure of complex molecules containing many different atoms. Such molecules in the process of chemical transformations can form not only medicinal substances, but also by-products that are harmful to the human body. Therefore, the pharmaceutical industry needs special "smart" catalysts that work "with atomic precision". "Smart" catalysts include metal complexes with N-heterocyclic carbenes, designated "M/NHC". M/NHC catalysts were discovered in the mid-1990s. It soon became clear that they have a number of unique features, which caused an explosive growth in the number of publications.
This project is aimed at creating new "smart" m/NHC catalysts. A key feature of the project is the use of special, functionally substituted heterocyclic carbenes. Their molecules have a special group called functional. A functional group is the part of a molecule that can engage in specific reactions. For example, the figure below shows the structural formula of such a substance. In this molecule, the functional group is the amino group (NH2). The following is a "photo" of the molecule obtained by x-ray diffraction analysis. This substance was first studied in this project.
In the production of drugs, it is necessary to change the structure of complex molecules containing many different atoms. Such molecules in the process of chemical transformations can form not only medicinal substances, but also by-products that are harmful to the human body. Therefore, the pharmaceutical industry needs special "smart" catalysts that work "with atomic precision". "Smart" catalysts include metal complexes with N-heterocyclic carbenes, designated "M/NHC". M/NHC catalysts were discovered in the mid-1990s. It soon became clear that they have a number of unique features, which caused an explosive growth in the number of publications.
This project is aimed at creating new "smart" m/NHC catalysts. A key feature of the project is the use of special, functionally substituted heterocyclic carbenes. Their molecules have a special group called functional. A functional group is the part of a molecule that can engage in specific reactions. For example, the figure below shows the structural formula of such a substance. In this molecule, the functional group is the amino group (NH2). The following is a "photo" of the molecule obtained by x-ray diffraction analysis. This substance was first studied in this project.
Why do we need a functional group in a catalyst molecule? What function does it have?
The functional group allows you to purposefully change the properties of the catalyst under certain external influences. For example, groups capable of acid-base dissociation strongly affect the solubility of the catalyst when the acidity of the medium changes. This makes it easier to separate the catalyst from the reaction products after synthesis. Some functional groups increase the stability of the catalyst by reacting reversibly with the components of reaction mixtures. In addition, such groups can be used to "attach" the catalyst to the surface of a solid carrier, making it heterogeneous. A heterogeneous catalyst can be used repeatedly, since it is insoluble in the reaction mixture and easily separates from the reaction products.
In this project, we were able to introduce new heterocyclic carbenes containing a free amino group into the chemistry of M/NHC complexes for the first time. The problem was that metals usually form strong bonds with amino groups. Therefore, the synthesis of M/NHC complexes with heterocyclic carbenes having free amino groups has been considered a problem until now. We first obtained palladium, Nickel, and gold complexes with amino-substituted NHC ligands-1,2,4-triazole derivatives, and for the first time showed the possibility of using an amino group to purposefully change the properties of M/NHC complexes by various reactions without changing the rest of the molecule. Moreover, it is shown for the first time that such m/NHC complexes can be synthesized directly from amino-substituted precursors of NHC ligands and metal salts, bypassing the stages of protection of the amino group.
Based on the results of the first year of research, an article was published in the highly rated journal Catalyst Science & Technology (DOI: 10.1039/c9cy02041a), which received very good reviews from reviewers.
In the next stages of the project, it is planned to expand the range of m/NHC complexes containing functional groups. It is planned to obtain new types of functionally substituted carbenes, synthesize new complexes with different metals from them, and study in detail the possibilities of these molecules in catalysis. As a result, we hope to create new "smart" catalysts that will allow us to conduct reactions of complex substances "with atomic precision".
The functional group allows you to purposefully change the properties of the catalyst under certain external influences. For example, groups capable of acid-base dissociation strongly affect the solubility of the catalyst when the acidity of the medium changes. This makes it easier to separate the catalyst from the reaction products after synthesis. Some functional groups increase the stability of the catalyst by reacting reversibly with the components of reaction mixtures. In addition, such groups can be used to "attach" the catalyst to the surface of a solid carrier, making it heterogeneous. A heterogeneous catalyst can be used repeatedly, since it is insoluble in the reaction mixture and easily separates from the reaction products.
In this project, we were able to introduce new heterocyclic carbenes containing a free amino group into the chemistry of M/NHC complexes for the first time. The problem was that metals usually form strong bonds with amino groups. Therefore, the synthesis of M/NHC complexes with heterocyclic carbenes having free amino groups has been considered a problem until now. We first obtained palladium, Nickel, and gold complexes with amino-substituted NHC ligands-1,2,4-triazole derivatives, and for the first time showed the possibility of using an amino group to purposefully change the properties of M/NHC complexes by various reactions without changing the rest of the molecule. Moreover, it is shown for the first time that such m/NHC complexes can be synthesized directly from amino-substituted precursors of NHC ligands and metal salts, bypassing the stages of protection of the amino group.
Based on the results of the first year of research, an article was published in the highly rated journal Catalyst Science & Technology (DOI: 10.1039/c9cy02041a), which received very good reviews from reviewers.
In the next stages of the project, it is planned to expand the range of m/NHC complexes containing functional groups. It is planned to obtain new types of functionally substituted carbenes, synthesize new complexes with different metals from them, and study in detail the possibilities of these molecules in catalysis. As a result, we hope to create new "smart" catalysts that will allow us to conduct reactions of complex substances "with atomic precision".