Facile Synthesis of Carbamoyl Fluorides -Carbamoylimidazole Activation

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2025 Mar 3

PMID 40028114

Authors

Anze Meden

Damijan Knez

Stanislav Gobec

Affiliations

Soon will be listed here.

Abstract

The untapped potential of carbamoyl fluorides for various chemico/biological applications is hampered by the scarcity of straightforward and benign methods for their synthesis. In this report, we disclose a novel mild three-step procedure that avoids exotic, corrosive, and highly toxic reagents. Briefly, commercially available secondary amines are carbamoylated with 1,1'-carbonyldiimidazole, followed by alkylation to improve nucleofugality, and exchange with inorganic KF. This procedure works on a gram scale without chromatographic purification. It is however limited to basic, sterically unhindered secondary amines without alkylation-prone functional groups.

References

MYERS D, KEMP Jr A . Inhibition of esterases by the fluorides of organic acids. Nature. 1954; 173(4392):33-4. DOI: 10.1038/173033a0. View

Cho H, Jang S, Lee K, Cha D, Min S . Visible-Light-Induced DDQ-Catalyzed Fluorocarbamoylation Using CFSONa and Oxygen. Org Lett. 2023; 25(48):8558-8563. DOI: 10.1021/acs.orglett.3c03335. View

Song J, Lim H . Synthesis of Carbamoyl Fluorides via a Selective Fluorinative Beckmann Fragmentation. Org Lett. 2021; 23(14):5394-5399. DOI: 10.1021/acs.orglett.1c01721. View

Yanachkov I, Dix E, Yanachkova M, Wright G . P1,P2-diimidazolyl derivatives of pyrophosphate and bis-phosphonates--synthesis, properties, and use in preparation of dinucleoside tetraphosphates and analogs. Org Biomol Chem. 2010; 9(3):730-8. PMC: 5705240. DOI: 10.1039/c0ob00542h. View

Zhang H, Wang Y, Wang Y, Li X, Wang S, Wang Z . Recent advance on carbamate-based cholinesterase inhibitors as potential multifunctional agents against Alzheimer's disease. Eur J Med Chem. 2022; 240:114606. DOI: 10.1016/j.ejmech.2022.114606. View

Yang Y, Taponard A, Vantourout J, Tlili A . Synthesis of Fluorinated Amines: A Personal Account. ACS Org Inorg Au. 2023; 3(6):364-370. PMC: 10704584. DOI: 10.1021/acsorginorgau.3c00029. View

Passia M, Demaerel J, Amer M, Drichel A, Zimmer S, Bolm C . Acid-Mediated Imidazole-to-Fluorine Exchange for the Synthesis of Sulfonyl and Sulfonimidoyl Fluorides. Org Lett. 2022; 24(48):8802-8805. DOI: 10.1021/acs.orglett.2c03546. View

Gale P, Hiscock J, Lalaoui N, Light M, Wells N, Wenzel M . Benzimidazole-based anion receptors: tautomeric switching and selectivity. Org Biomol Chem. 2012; 10(30):5909-15. DOI: 10.1039/c1ob06800h. View

Liu L, Gu Y, Zhang C . Recent Advances in the Synthesis and Transformation of Carbamoyl Fluorides, Fluoroformates, and Their Analogues. Chem Rec. 2023; 23(9):e202300071. DOI: 10.1002/tcr.202300071. View

10.

Bonnefoy C, Chefdeville E, Tourvieille C, Panossian A, Hanquet G, Leroux F . Study of Carbamoyl Fluoride: Synthesis, Properties and Applications. Chemistry. 2022; 28(43):e202201589. DOI: 10.1002/chem.202201589. View

11.

Meden A, Knez D, Brazzolotto X, Nachon F, Dias J, Svete J . From tryptophan-based amides to tertiary amines: Optimization of a butyrylcholinesterase inhibitor series. Eur J Med Chem. 2022; 234:114248. DOI: 10.1016/j.ejmech.2022.114248. View

12.

Tsukamoto H, Kahne D . N-methylimidazolium chloride-catalyzed pyrophosphate formation: application to the synthesis of Lipid I and NDP-sugar donors. Bioorg Med Chem Lett. 2011; 21(17):5050-3. PMC: 3156252. DOI: 10.1016/j.bmcl.2011.04.061. View

13.

Scattolin T, Bouayad-Gervais S, Schoenebeck F . Straightforward access to N-trifluoromethyl amides, carbamates, thiocarbamates and ureas. Nature. 2019; 573(7772):102-107. DOI: 10.1038/s41586-019-1518-3. View

14.

Turksoy A, Scattolin T, Bouayad-Gervais S, Schoenebeck F . Facile Access to AgOCF and Its New Applications as a Reservoir for OCF for the Direct Synthesis of N-CF , Aryl or Alkyl Carbamoyl Fluorides. Chemistry. 2020; 26(10):2183-2186. DOI: 10.1002/chem.202000116. View

15.

Johnson M . Sensitivity and selectivity of compounds interacting with neuropathy target esterase. Further structure-activity studies. Biochem Pharmacol. 1988; 37(21):4095-104. DOI: 10.1016/0006-2952(88)90101-3. View

16.

Li Y, Zhang F, Wang R, Qi S, Luan Y, Ye M . Carbamoyl Fluoride-Enabled Enantioselective Ni-Catalyzed Carbocarbamoylation of Unactivated Alkenes. J Am Chem Soc. 2020; 142(47):19844-19849. DOI: 10.1021/jacs.0c09949. View

17.

Cadwallader D, Tiburcio T, Cieszynski G, Le C . Synthesis of Carbamoyl Fluorides Using a Difluorophosgene Surrogate Derived from Difluorocarbene and Pyridine -Oxides. J Org Chem. 2022; 87(17):11457-11468. DOI: 10.1021/acs.joc.2c01017. View

18.

Nielsen C, Zivkovic F, Schoenebeck F . Synthesis of -CF Alkynamides and Derivatives Enabled by Ni-Catalyzed Alkynylation of -CF Carbamoyl Fluorides. J Am Chem Soc. 2021; 143(33):13029-13033. DOI: 10.1021/jacs.1c07780. View

19.

Xing S, Li Q, Xiong B, Chen Y, Feng F, Liu W . Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer's disease, and fat metabolism. Med Res Rev. 2020; 41(2):858-901. DOI: 10.1002/med.21745. View

20.

METZGER H, Wilson I . EVIDENCE FOR AN ELECTROPHILIC MECHANISM IN CATALYSIS BY HYDROLYTIC ENZYMES. Biochemistry. 1964; 3:926-31. DOI: 10.1021/bi00895a013. View