2020 Fiscal Year Research-status Report
Development of sustainable heterogeneous catalysts for step-efficient synthesis of selective oncology drug intermediates.
| Project/Area Number |
20K05576
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
Siddiki Hakim 北海道大学, 触媒科学研究所, 特任助教 (60722650)
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | Heterogeneous Catalysis / Step-efficient Synthesis / Oncology drug |
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| Outline of Annual Research Achievements |
To develop the heterogeneous catalytic methods for the proposed plan, the reactions including (1) Hydrolysis of amides to form carboxylic acids, (2) Heterocyclization of aminoalcohols with alcohols to form pyridine derivatives, and (3) Challenging selective methylation of 1,2 diamino benzene to form benzimidazole are being demonstrated employing sustainable and environmentally benign green synthesis methods under the acceptorless dehydrogenative coupling strategy and acid base mediated hydrolysis reactions. In addition to these the effective catalyst for the dehydrogenative hetero-cyclization of 2-aminobenzamide derivative and 1,2-diaminobenzene derivative to the desired oncology drug intermediate that is quinazolin-4-amine and benzimidazole are being assigned and further kinetic and mechanistic studies are underway.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Dehydrogenative selective methylation and reductive amination of 2-aminobenzamide derivative to quinazolin-4-amine derivative was performed in a two steps reaction. Step-1 methylation to form quinazolinone derivative, and step-2 reductive amination of quinazolinone derivative to form quinazolin-4-amine derivative in reaction with methanol and gaseous ammonia using supported Pt nanoparticles catalysts resulted in >70% yield with >80% selectivity to the desired heterocylces. Additionally reaction of 1,2-diamino benzene derivative with methanol produced benzimidazole derivative with 65% yield and 75% selectivity using the same catalytic system. The developed catalytic system proceeds under solvent-free, oxidant free conditions with the generation of environmentally benign gaseous hydrogen and water the only byproducts.
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| Strategy for Future Research Activity |
A series of metal oxides including acidic, basic, amphoteric supports and different metals nanoparticles are being planned to teste for these dehydrogenative hetero cyclization reactions. Further optimization of the reaction conditions will be demonstrated to achieve the highest efficiency and selectivity. Heterogeneous properties including catalyst reusability, metal leaching and related experiment and analyses are being designed to perform for the most effective catalysts in the synthesis of quinazolin-4-amine and benzimidazole derivative. Kinetic and mechanistic studies will also be revealed. DFT calculations and in situ spectroscopic methods are being planned which can be apply for this study. Novel and efficient heterogeneous sustainable catalytic systems would be realized on the basis of the established guidelines.
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