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DOI: 10.1055/a-2522-6819
Thermal-Mediated Synthesis of Hydantoin Derivatives from Amino Acids via Carbodiimide Reagents
This study was supported by Türkiye Bilimsel ve Teknolojik Araştırma Kurumu (TUBITAK) under grant number 123Z894. The authors thank TUBITAK for the support.
Abstract
We introduce an innovative methodology for synthesizing hydantoins from amino acids using readily available carbodiimides, emphasizing the crucial role of temperature in the reaction process. This approach presents significant advantages over conventional methods involving isocyanates, facilitating easier handling and minimizing associated risks. Our strategy not only allows for the efficient production of a diverse array of hydantoin derivatives but also adheres to environmentally sustainable practices. The optimized reaction conditions enhance efficiency, marking a significant advancement in the field of organic synthesis. This method presents significant advantages for industrial applications, as it is a heat-mediated process that does not require the use of any bases or catalysts. By eliminating the need for additional reagents, this approach simplifies the reaction conditions, reduces potential side reactions, and minimizes the overall environmental impact. Additionally, the absence of catalysts streamlines the purification process, making it more cost-effective and efficient for large-scale production.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2522-6819.
- Supporting Information
Publication History
Received: 04 January 2025
Accepted after revision: 22 January 2025
Accepted Manuscript online:
22 January 2025
Article published online:
12 March 2025
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- 18 General Procedure A Amino acid (0.3 mmol) and carbodiimide (1.2 equiv) were stirred in 2 mL of dioxane at 80 °C for 4 h. Then, the reaction mixture was concentrated under vacuum. The crude product was purified by silica gel column chromatography using DCM/EtOAc as the eluent. General Procedure B A solution of the amino acid (0.3 mmol) and carbodiimide (1.2 equiv) in dioxane (2 mL) was refluxed (100 °C) for 9 h. Then, the reaction mixture was concentrated under vacuum. The crude product was purified by silica gel column chromatography using DCM/EtOAc as the eluent.