Skip to main content

Advertisement

SpringerLink
Log in

Photochemical Csp2–H bond thiocyanation and selenocyanation of activated arenes, batch and continuous-flow approaches

  • Original Papers
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Herein, we report an eco-friendly photochemical oxidative Csp2–H thiocyanation and selenocyanation of activated arenes. The reaction proceeds under Violet LED irradiation in the presence of K2S2O8, which quickly oxidizes KSCN and KSeCN, finally producing arylthio/selenocyanates. Using this benign, atom-economic protocol, the desired chalcogenide products were obtained regioselectively, with isolated yields that range from very good to excellent. Although, mechanistic study indicates that it is difficult to distinguish between a radical to a SEAr reaction mechanism between the photo-induced formed •SCN, for the former, or NCSSCN, for the latter, to the aromatic heterocycles. The inhibition experiment together with the observed reactivity and regioselectivity, would be in agreement with the latter. The synthetic methodology designed could be successfully adapted to continuous-flow systems in a segmented-flow regime, employing the organic phase as the product reservoir. Using this setup, the advantage of the latter can be demonstrated by reducing the reaction time and improving the product yields. Similarly, the scaling up of the reaction to gram scale resulted in favorable outcomes by the flow setup, which installs the photo-flow chemistry as a powerful tool to be included into routine reaction procedures, which have great relevance for the pharmaceutical industry.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7
Scheme 8
Scheme 9
Scheme 10
Scheme 11

Similar content being viewed by others

References

  1. Liu, G., Huth, J. R., Olejniczak, E. T., Mendoza, R., DeVries, P., Leitza, S., & von Geldern, T. W. (2001). Novel p -Arylthio Cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties. Journal of Medicinal Chemistry, 44(8), 1202–1210. https://doi.org/10.1021/jm000503f

    Article  CAS  PubMed  Google Scholar 

  2. Clader, J. W., Billard, W., Binch, H., 3rd., Chen, L.-Y., Crosby, G. J., Duffy, R. A., & Greenlee, W. J. (2004). Muscarinic M2 antagonists: Anthranilamide derivatives with exceptional selectivity and in vivo activity. Bioorganic & medicinal chemistry, 12(2), 319–326. https://doi.org/10.1016/j.bmc.2003.11.005

    Article  CAS  Google Scholar 

  3. Gouda, A. M., & Abdelazeem, A. H. (2016). An integrated overview on pyrrolizines as potential anti-inflammatory, analgesic and antipyretic agents. European Journal of Medicinal Chemistry, 114, 257–292. https://doi.org/10.1016/j.ejmech.2016.01.055

    Article  CAS  PubMed  Google Scholar 

  4. Kaldor, S. W., Kalish, V. J., Davies, J. F., Shetty, B. V., Fritz, J. E., Appelt, K., & Tatlock, J. H. (1997). Viracept (Nelfinavir Mesylate, AG1343): A potent, orally bioavailable inhibitor of HIV-1 protease. Journal of Medicinal Chemistry, 40(24), 3979–3985. https://doi.org/10.1021/jm9704098

    Article  CAS  PubMed  Google Scholar 

  5. Gueye, M. N., Carella, A., Faure-Vincent, J., Demadrille, R., & Simonato, J.-P. (2020). Progress in understanding structure and transport properties of PEDOT-based materials: A critical review. Progress in Materials Science, 108, 100616. https://doi.org/10.1016/j.pmatsci.2019.100616

    Article  CAS  Google Scholar 

  6. Kelly, T. R., Kim, M. H., & Curtis, A. D. M. (1993). Structure correction and synthesis of the naturally occurring benzothiazinone BMY 40662. The Journal of Organic Chemistry, 58(21), 5855–5857. https://doi.org/10.1021/jo00073a057

    Article  CAS  Google Scholar 

  7. Wu, J., Wu, G., & Wu, L. (2008). Thiocyanation of aromatic and heteroaromatic compounds using ammonium thiocyanate and I2O5. Synthetic Communications, 38(14), 2367–2373. https://doi.org/10.1080/00397910802139254

    Article  CAS  Google Scholar 

  8. Mahajan, U. S., & Akamanchi, K. G. (2009). Facile method for thiocyanation of activated arenes using iodic acid in combination with ammonium thiocyanate. Synthetic Communications, 39(15), 2674–2682. https://doi.org/10.1080/00397910802663402

    Article  CAS  Google Scholar 

  9. Mete, T. B., Khopade, T. M., & Bhat, R. G. (2017). Transition-metal-free regioselective thiocyanation of phenols, anilines and heterocycles. Tetrahedron Letters, 58(5), 415–418. https://doi.org/10.1016/j.tetlet.2016.12.043

    Article  CAS  Google Scholar 

  10. Dai, P., Li, C., Li, Y., Xia, Q., Zhang, M., Gu, Y.-C., & Zhang, W.-H. (2020). Transition-metal-free Csp 2 −H regioselective thiocyanation of free anilines. Asian Journal of Organic Chemistry, 9(10), 1585–1588. https://doi.org/10.1002/ajoc.202000400

    Article  CAS  Google Scholar 

  11. Nair, V., Augustine, A., & George, T. G. (2002). A facile CAN-mediated synthesis of selenocyanates from arylalkenes and heteroarenes. European Journal of Organic Chemistry, 2002(14), 2363. https://doi.org/10.1002/1099-0690(200207)2002:14%3c2363::AID-EJOC2363%3e3.0.CO;2-7

    Article  Google Scholar 

  12. Fan, W., Yang, Q., Xu, F., & Li, P. (2014). A visible-light-promoted aerobic metal-free C-3 thiocyanation of indoles. The Journal of Organic Chemistry, 79(21), 10588–10592. https://doi.org/10.1021/jo5015799

    Article  CAS  PubMed  Google Scholar 

  13. Mitra, S., Ghosh, M., Mishra, S., & Hajra, A. (2015). Metal-Free thiocyanation of imidazoheterocycles through visible light photoredox catalysis. The Journal of Organic Chemistry, 80(16), 8275–8281. https://doi.org/10.1021/acs.joc.5b01369

    Article  CAS  PubMed  Google Scholar 

  14. Hosseini-Sarvari, M., Hosseinpour, Z., & Koohgard, M. (2018). Visible light thiocyanation of N-bearing aromatic and heteroaromatic compounds using Ag/TiO2 nanotube photocatalyst. New Journal of Chemistry, 42(23), 19237–19244. https://doi.org/10.1039/C8NJ03128B

    Article  CAS  Google Scholar 

  15. Zhang, W., Tang, J., Yu, W., Huang, Q., Fu, Y., Kuang, G., & Yu, G. (2018). Visible light-driven C-3 functionalization of indoles over conjugated microporous polymers. ACS Catalysis, 8(9), 8084–8091. https://doi.org/10.1021/acscatal.8b01478

    Article  CAS  Google Scholar 

  16. Zhang, J., Wang, H., Chen, Y., Xie, H., Ding, C., Tan, J., & Xu, K. (2020). Electrochemical synthesis of selenocyanated imidazo[1,5-a]quinolines under metal catalyst- and chemical oxidant-free conditions. Chinese Chemical Letters, 31(6), 1576–1579. https://doi.org/10.1016/j.cclet.2019.11.037

    Article  CAS  Google Scholar 

  17. Fotouhi, L., & Nikoofar, K. (2013). Electrochemical thiocyanation of nitrogen-containing aromatic and heteroaromatic compounds. Tetrahedron Letters, 54(23), 2903–2905. https://doi.org/10.1016/j.tetlet.2013.02.106

    Article  CAS  Google Scholar 

  18. Wen, J., Niu, C., Yan, K., Cheng, X., Gong, R., Li, M., & Wang, H. (2020). Electrochemical-induced regioselective C-3 thiomethylation of imidazopyridines: Via a three-component cross-coupling strategy. Green Chemistry, 22(4), 1129–1133. https://doi.org/10.1039/c9gc04068d

    Article  CAS  Google Scholar 

  19. Colomer, J. P., Traverssi, M., & Oksdath-Mansilla, G. (2020). Oxidation of organosulfur compounds promoted by continuous-flow chemistry. Journal of Flow Chemistry, 10(1), 123–138. https://doi.org/10.1007/s41981-019-00066-5

    Article  CAS  Google Scholar 

  20. Buglioni, L., Raymenants, F., Slattery, A., Zondag, S. D. A., & Noël, T. (2021). Technological innovations in photochemistry for organic synthesis: Flow chemistry, high-throughput experimentation, scale-up, and photoelectrochemistry. Chemical Reviews. https://doi.org/10.1021/acs.chemrev.1c00332

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sambiagio, C., & Noël, T. (2020). Flow photochemistry: Shine some light on those tubes! Trends in Chemistry, 2(2), 92–106. https://doi.org/10.1016/j.trechm.2019.09.003

    Article  CAS  Google Scholar 

  22. Politano, F., & Oksdath-Mansilla, G. (2018). Light on the horizon: Current research and future perspectives in flow photochemistry. Organic Process Research & Development, 22(9), 1045–1062. https://doi.org/10.1021/acs.oprd.8b00213

    Article  CAS  Google Scholar 

  23. Ötvös, S. B., & Kappe, C. O. (2021). Continuous flow asymmetric synthesis of chiral active pharmaceutical ingredients and their advanced intermediates. Green Chemistry, 23(17), 6117–6138. https://doi.org/10.1039/D1GC01615F

    Article  PubMed  PubMed Central  Google Scholar 

  24. Monbaliu, J.-C.M., Stelzer, T., Revalor, E., Weeranoppanant, N., Jensen, K. F., & Myerson, A. S. (2016). Compact and integrated approach for advanced end-to-end production, purification, and aqueous formulation of lidocaine hydrochloride. Organic Process Research & Development, 20(7), 1347–1353. https://doi.org/10.1021/acs.oprd.6b00165

    Article  CAS  Google Scholar 

  25. Gérardy, R., Winter, M., Vizza, A., & Monbaliu, J.-C.M. (2017). Assessing inter- and intramolecular continuous-flow strategies towards methylphenidate (Ritalin) hydrochloride. Reaction Chemistry & Engineering, 2(2), 149–158. https://doi.org/10.1039/C6RE00184J

    Article  Google Scholar 

  26. Gao, X., Liu, J., Zuo, X., Feng, X., & Gao, Y. (2020). Recent advances in synthesis of Benzothiazole compounds related to green chemistry. Molecules, 25(7), 1675. https://doi.org/10.3390/molecules25071675

    Article  CAS  PubMed Central  Google Scholar 

  27. Weeranoppanant, N. (2019). Enabling tools for continuous-flow biphasic liquid–liquid reaction. Reaction Chemistry & Engineering, 4(2), 235–243. https://doi.org/10.1039/C8RE00230D

    Article  CAS  Google Scholar 

  28. Tsitonaki, Ai., Petri, B., Crimi, M., Mosbaek, H., Siegrist, R. L., & Bjerg, P. L. (2010). In situ chemical oxidation of contaminated soil and groundwater using persulfate: A review. Critical Reviews in Environmental Science and Technology, 40(1), 55–91. https://doi.org/10.1080/10643380802039303

    Article  CAS  Google Scholar 

  29. Liu, K., Song, W., Deng, Y., Yang, H., Song, C., Abdelilah, T., & Lei, A. (2020). Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives. Nature Communications, 11(1), 1–11. https://doi.org/10.1038/s41467-019-13829-4

    Article  CAS  Google Scholar 

  30. Milosavljevic, B. H., & LaVerne, J. A. (2005). Pulse radiolysis of aqueous thiocyanate solution. The Journal of Physical Chemistry A, 109(1), 165–168. https://doi.org/10.1021/jp046088a

    Article  CAS  PubMed  Google Scholar 

  31. Bouchet, L. M., Peñéñory, A. B., Robert, M., & Argüello, J. E. (2015). Breaking bonds with electrons: Stepwise and concerted reductive cleavage of C-S, C–Se and Se–CN bonds in phenacylthiocyanates and phenacylselenocyanates. RSC Advances, 5(16), 11753–11760. https://doi.org/10.1039/C4RA16154H

    Article  CAS  Google Scholar 

  32. Alfassi, Z. B., Huie, R. E., Mosseri, S., & Neta, P. (1987). Kinetics of one-electron oxidation by the cyanate radical. The Journal of Physical Chemistry, 91(14), 3888–3891. https://doi.org/10.1021/j100298a031

    Article  CAS  Google Scholar 

  33. Sarla, M., Pandit, M., Tyagi, D. K., & Kapoor, J. C. (2004). Oxidation of cyanide in aqueous solution by chemical and photochemical process. Journal of hazardous materials, 116(1–2), 49–56. https://doi.org/10.1016/j.jhazmat.2004.06.035

    Article  CAS  PubMed  Google Scholar 

  34. Chaulet, C., Croix, C., Basset, J., Pujol, M.-D., & Viaud-Massuard, M.-C. (2010). Desulfonylation of indoles and 7-Azaindoles using sodium tert-Butoxide. Synlett, 2010(10), 1481–1484. https://doi.org/10.1055/s-0029-1219918

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Secretaría de Ciencia y Tecnología (SeCyT), Universidad Nacional de Córdoba (UNC), and Fondo para la Investigación Científica y Tecnológica Argentina (FONCyT). I-L gratefully acknowledges receipt of a fellowship from CONICET.

Author information

Authors and Affiliations

  1. INFIQC-CONICET-UNC, Dpto. de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Ciudad Universitaria, X5000HUA, Córdoba, Argentina

    Ignacio D. Lemir, Gabriela Oksdath-Mansilla, Luciana C. Schmidt & Juan E. Argüello

  2. CENSALUD-UES, Dpto. de Química, Física y Matemática, Facultad de Química y Farmacia, Universidad de El Salvador, Final Av. de Mártires y Héroes del 30 de Julio, San Salvador, 1101, El Salvador

    Willber D. Castro-Godoy

Authors
  1. Ignacio D. Lemir
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabriela Oksdath-Mansilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Willber D. Castro-Godoy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Luciana C. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Juan E. Argüello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Juan E. Argüello.

Ethics declarations

Conflict of interest

The authors have no conflicts to disclose.

Ethical approval

Not applicable.

Consent to participate

All authors gave their consent to participate.

Consent for publication

All authors gave their consent to publish.

Additional information

Dedications: Dedicated to Prof. Angelo Albino on occasion of his 75th anniversary.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 3846 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lemir, I.D., Oksdath-Mansilla, G., Castro-Godoy, W.D. et al. Photochemical Csp2–H bond thiocyanation and selenocyanation of activated arenes, batch and continuous-flow approaches. Photochem Photobiol Sci 21, 849–861 (2022). https://doi.org/10.1007/s43630-021-00167-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43630-021-00167-y

Keywords

Search

Navigation