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PreprintCC BYChemRxiv

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

  • Xiangmei Kong1
  • Tianxing Lin1
  • Zhenbo Guo1
  • Yunfei Liang1
  • Shanhui Zhu1
  • Qinbo Jiao2,3
  • Chunfa Xu2,3
  • Liang-Nian He1
  • Tianfei Liu1,4
  • Jin-Pei Cheng5,6
6 affiliations
  1. 1State Key Laboratory of Elemento-organic Chemistry, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Weijin Road No. 94, Tianjin, China, 300071
  2. 2Key Laboratory of Molecule Synthesis and Function Discovery, College of Chemistry
  3. 3Fuzhou University
  4. 4Haihe Laboratory of Sustainable Chemical Transformations
  5. 5Department of Chemistry
  6. 6Tsinghua University
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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 .

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Cite

BibTeXRIS
BibTeX
@misc{kong2026synthesizing,
  title = {{Synthesizing N-indole Carbamates via CO2 Valorization in o-difluorobenzene driven by pKa Values of N-H Covalent Bonds}},
  author = {Xiangmei Kong and Tianxing Lin and Zhenbo Guo and Yunfei Liang and Shanhui Zhu and Qinbo Jiao and Chunfa Xu and Liang-Nian He and Tianfei Liu and Jin-Pei Cheng},
  howpublished = {ChemRxiv},
  year = {2026},
  month = sep,
  doi = {10.26434/chemrxiv.15008938/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008938/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Synthesizing N-indole Carbamates via CO2 Valorization in o-difluorobenzene driven by pKa Values of N-H Covalent Bonds
AU  - Xiangmei Kong
AU  - Tianxing Lin
AU  - Zhenbo Guo
AU  - Yunfei Liang
AU  - Shanhui Zhu
AU  - Qinbo Jiao
AU  - Chunfa Xu
AU  - Liang-Nian He
AU  - Tianfei Liu
AU  - Jin-Pei Cheng
PY  - 2026
DA  - 2026/09/16
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15008938/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15008938/v1
AB  - 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 .
ER  -