Work

Synthesizing N-indole Carbamates via CO2 Valorization in o-difluorobenzene driven by pKa Values of N-H Covalent Bonds

Year: 2026

Type: preprint

Abstract: A green synthetic route for accessing N -indole carbamates, a key building block of bioactive molecules, can be achieved using indole and CO 2 . However, using strong bases results in low yields and reduced functional group tolerance, making it more challenging to develop milder reactions. The proton transfer from indole N-H bond to base is one of the essential steps in synthesizing N-indole carbamates, which is highly dependent on the driving force ΔG PT and their corresponding p K a values in the solution-state. In this study, the optimized condition was experimentally approved and driven by the ΔG PT values derived from the experimentally determined pKa values of 31 N–H covalent bonds in six polar fluorinated arenes, resulting in synthesizing N-indole carbamates in o-difluorobenzene promoted by MTBD via CO 2 valorization at room temperature, which is free of catalysts or additives and exhibits excellent functional group tolerance with moderate to excellent yields. Compared to commonly used organic solvents like THF and acetonitrile, the ΔG PT can be significantly reduced in o-difluorobenzene. And DFT analysis revealed that o-DFB can regulate the reaction mechanism through a pathway in which indole anionic intermediate formed before the activation of CO 2 .

Source: ChemRxiv

DOI: 10.26434/chemrxiv.15008938/v1