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Photochemical electrocyclic ring closure and leaving group expulsion from N-(9-oxothioxanthenyl)benzothiophene carboxamides

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Abstract

N-(9-Oxothioxanthenyl)benzothiophene carboxamides bearing leaving groups (LG− = Cl−, PhS−, HS−, PhCH2S−) at the C-3 position of the benzothiophene ring system photochemically cyclize with nearly quantitative release of the leaving group, LG−. The LG− photoexpulsions can be conducted with 390 nm light or with a sunlamp. Solubility in 75% aqueous CH3CN is achieved by introducing a carboxylate group at the C-6 position of the benzothiophene ring. The carboxylate and methyl ester derivatives regiospecifically cyclize at the more hindered C-1 position of the thioxanthone ring. Otherwise, the photocyclization favors the C-3 position of the thioxanthone. Quantum yields for reaction are 0.01–0.04, depending on LG− basicity. Electronic structure calculations for the triplet excited state show that excitation transfer occurs from the thioxanthone to the benzothiophene ring. Subsequent cyclization in the triplet excited state is energetically favourable and initially generates the triplet excited state of the zwitterionic species. Expulsion of LG− is thought to occur once this species converts to the closed shell ground state.

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Notes and references

  1. H.-M. Lee, D. R. Larson, D. S. Lawrence, Illuminating the chemistry of life: design, synthesis, and applications of “caged” and related photoresponsive compounds, ACS Chem. Biol., 2009, 4, 409–427. and references cited therein.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. G. Mayer, A. Heckel, Biologically active molecules with a light switch, Angew. Chem., Int. Ed., 2006, 45, 4900–4921.

    Article  CAS  Google Scholar 

  3. D. Warther, S. Gug, A. Specht, F. Bolze, J.-F. Nicoud, A. Mourot, M. Goeldner, Two-photon uncaging: new prospects in neuroscience and cellular biology, Biorg. Med. Chem., 2010, 18, 7753–7758.

    Article  CAS  Google Scholar 

  4. M. Sarker, T. Shahrin, M. G. Steinmetz, Photochemical eliminations involving zwitterionic intermediates generated via electrocyclic ring closure of benzothiophene carboxanilides, Org. Lett., 2011, 13, 872–875.

    Article  CAS  PubMed  Google Scholar 

  5. The nitrobenzyl group has been used as a photoremovable protecting group for sulfhydryl groups. 5b,c It should be noted that the expected byproduct upon photochemical release of thiol is a nitrosoarene, and in general, nitrosoarenes undergo chemical reduction by thiols.6.

  6. C.-Y. Chang, T. T. Fernandez, R. Panchal, H. Bayley, Caged catalytic subunit of cAMP-dependent protein kinase, J. Am. Chem. Soc., 1998, 120, 7661–7662.

    Article  CAS  Google Scholar 

  7. H. Bayley, C.-Y. Chang, W. T. Miller, B. Niblack, P. Pan, Caged peptides and proteins by targeted chemical modification, Methods Enzymol., 1998, 291, 117–135.

    Article  CAS  PubMed  Google Scholar 

  8. S. Montanari, C. Paradisi, G. Scorrano, Pathways of nitrosobenzene reduction by thiols in alcoholic media, J. Org. Chem., 1999, 64, 3422–3428.

    Article  CAS  PubMed  Google Scholar 

  9. A. Specht, S. Loudwig, L. Peng, M. Goeldner, p-Hydroxyphenacyl bromide as a photoremovable thiol label: a potential phototrigger for thiol-containing biomolecules, Tetrahedron Lett., 2002, 43, 8947–8950.

    Article  CAS  Google Scholar 

  10. J. W. Walker, S. H. Gilbert, R. M. Drummond, M. Yamada, R. Sreekumar, R. E. Carraway, M. Ikebe, F. S. Fay, Signaling pathways underlying eosinophil cell motility revealed by using caged peptides, Proc. Natl. Acad. Sci U. S. A., 1998, 95, 1568–1573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. H. Kimura, Hydrogen sulfide: its production, release, and functions, Amino Acids, 2011, 41, 113–121.

    Article  CAS  PubMed  Google Scholar 

  12. M. M. Gadalla, S. H. Snyder, Hydrogen sulfide as a gasotransmitter, J. Neurochem., 2010, 113, 14–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. J. K. Moon, J. W. Park, W. S. Lee, Y. J. Kang, H. A. Chung, M. S. Shin, Y. J. Yoon, Synthesis of some 2-substituted-thioxanthones, J. Heterocycl. Chem., 1999, 36, 793–798.

    Article  CAS  Google Scholar 

  14. W. B. Wright, H. J. Brabander, The preparation of 3-chlorobenzo[b] thiophene derivatives from cinnamic acids, J. Heterocycl. Chem., 1971, 8, 711–714.

    Article  CAS  Google Scholar 

  15. Z. Pechlivanidis, H. Hopf, L. Ernst, Paracyclophanes: extending the bridges. Synthesis, Eur. J. Org. Chem., 2009, 223–237.

    Google Scholar 

  16. R. A. Delden, J. H. Hurenkamp, B. L. Feringa, Photochemical and thermal isomerization processes of a chiral auxiliary based donor–acceptor substituted chiroptical molecular switch: convergent synthesis, improved resolution and switching properties, Chem.–Eur. J., 2003, 9, 2845–2853.

    Article  PubMed  CAS  Google Scholar 

  17. M. G. Neumann, M. H. Gehlen, M. V. Encinas, N. S. Allen, T. Corrales, C. Peinado, F. Catalina, Photophysics and photoreactivity of substituted thioxanthones, J. Chem. Soc., Faraday Trans., 1997, 93, 1517–1521.

    Article  CAS  Google Scholar 

  18. Y. Ilichev, M. A. Schworer, J. Wirz, Photochemical reaction mechanisms of 2-nitrobenzyl compounds: methyl ethers and caged ATP, J. Am. Chem. Soc., 2004, 126, 4581–4595.

    Article  CAS  Google Scholar 

  19. J. W. Walker, H. Martin, F. R. Schmitt, R. J. Barsotti, Rapid release of an α-adrenergic receptor ligand from photolabile analogues, Biochemistry, 1993, 32, 1338–1345.

    Article  CAS  PubMed  Google Scholar 

  20. K. Stensrud, J. Noh, K. Kandler, J. Wirz, D. Heger, R. S. Givens, Competing pathways in the photo-Favorskii rearrangement and release of esters: studies on fluorinated p-hydroxyphenacyl-caged GABA and glutamate phototriggers, J. Org. Chem., 2009, 74, 5219–5227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. R. S. Givens, J. F. W. Weber, A. H. Jung, C.-H. Park, New photoprotecting groups: desyl and p-hydroxyphenacyl phosphate and carboxylate esters, Methods Enzymol., 1998, 120, 1–29.

    Google Scholar 

  22. V. Hagen, J. Bendig, S. Frings, T. Eckardt, S. Helm, D. Reuter, U. B. Kaupp, Highly efficient and ultrafast phototriggers for cAMP and cGMP by using long-wavelength UV/Vis-activation, Angew. Chem., Int. Ed., 2001, 40, 1045–1048.

    Article  Google Scholar 

  23. T. Furuta, S. S.-H. Wang, J. L. Dantzker, T. M. Dore, W. J. Bybee, E. M. Callaway, W. Denk, R. Y. Tsien, Proc. Natl. Acad. Sci. U. S. A., 1999, 96, 1193–1200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. M. J. Davis, C. H. Kragor, K. G. Reddie, H. C. Wilson, Y. Zue, T. M. Dore, Substituent effects on the sensitivity of a quinoline photoremovable protecting group to one- and two-photon excitation, J. Org. Chem., 2009, 74, 1721–1729.

    Article  CAS  PubMed  Google Scholar 

  25. A. V. Pinheiro, A. J. Parola, P. V. Baptista, J. C. Lima, pH Effect on the photochemistry of 4-methylcoumarin phosphate esters: caged-phosphate case study, J. Phys. Chem. A., 2010, 114, 12795–12803.

    Article  CAS  PubMed  Google Scholar 

  26. R. Schmidt, D. Geissler, V. Hagen, J. Bendig, Mechanism of photocleavage of (coumarin-4-yl)methyl esters, J. Chem. Phys., 2007, 111, 5768–5774.

    Article  CAS  Google Scholar 

  27. V. San Miguel, C. G. Bochet, A. del Campo, Wavelength-selective caged surfaces: how many functional levels are possible?, J. Am. Chem. Soc., 2011, 133, 5380–5388.

    Article  CAS  PubMed  Google Scholar 

  28. For a review of two-photon uncaging, see:. H. Kasai, M. Matsuzaki and G. C. R. Ellis-Davies, A. Konnerth, Cold Spring Harbor, New York, 2005, pp. 275–

    Google Scholar 

  29. With arylthiols efficient quenching 25b of benzophenone by hydrogen transfer results in thiyl and ketyl radicals, 25c which regenerate starting materials by disproportionation more rapidly than homocoupling to pinacol and disulfide. 25b–e With mesitylmercaptan and benzophenone a quantum yield of 0.1 has been reported for disulfide formation. 25d We did not observe disulfide or pinacol products in our study. A computational study indicates that such disporportionation will be facile. 25e An alternate mechanism for quenching is electron transfer and rapid back electron transfer, which may be more important for alkylthiols than arylthiols. 25c.

  30. J. B. Guttenplan, S. G. Cohen, Quenching and reduction of photoexcited benzophenone by thioethers and mercaptans, J. Org. Chem., 1973, 38, 2001–2007.

    Article  CAS  Google Scholar 

  31. S. Inbar, H. Linschitz, S. G. Cohen, Quenching and radical formation in the reaction of photoexcited benzophenone with thiols and thioethers (sulfides). Nanosecond flash studies, J. Am. Chem. Soc., 1982, 104, 1679–1682.

    Article  CAS  Google Scholar 

  32. S. G. Cohen, A. W. Rose, P. G. Stone, A. Ehret, Competitive processes in retardation by mercaptans of photoreduction by alcohols, J. Am. Chem. Soc., 1979, 101, 1827–1832.

    Article  CAS  Google Scholar 

  33. H. Cardy, E. Poquet, M. Chaillet, J. Ollivier, Ab initio CI study of hydrogen abstraction from hydrogen and methyl sulphide by ketone triplet excited state, Chem. Phys., 1993, 79–90.

    Google Scholar 

  34. J. Beltowski, Hypoxia in the renal medulla: implications for H2S signaling, J. Pharmacol. Exp. Ther., 2010, 334, 358–363.

    Article  CAS  PubMed  Google Scholar 

  35. H. Zhao, H. Wang, M. Xian, Cysteine-activated hydrogen sulfide (H2S) donors, J. Am. Chem. Soc., 2011, 133, 15–17.

    Article  CAS  PubMed  Google Scholar 

  36. O. Rubio-Pons, L. Serrano-Andres, D. Burget, P. Jacques, A butterfly like motion as a clue to the photophysics of thioxanthone, J. Photochem. Photobiol., A: Chem., 2006, 179, 298–304.

    Article  CAS  Google Scholar 

  37. X. Allonas, C. Ley, C. Bibaut, P. Jacques, J. P. Fouassier, Investigation of the triplet quantum yield of thioxanthone by time-resolved thermal lens spectroscopy: solvent and population lens effects, Chem. Phys. Lett., 2000, 322, 483–490.

    Article  CAS  Google Scholar 

  38. J. Seixas de Melo, L. M. Rodrigues, C. Serpa, L. G. Arnaut, I. C. F. R. Ferreira, M.-J. R. P. Queiroz, Photochemistry and photophysics of thienocarbazoles, Photochem. Photobiol., 2003, 77, 121–128.

    Article  CAS  PubMed  Google Scholar 

  39. B. Wex, B. R. Kaafarani, E. O. Danilov, D. C. Neckers, Altering the emission behavior with the turn of a thiophene ring: the photophysics of condensed ring systems of alternating benzenes and thiophenes, J. Phys. Chem. A., 2006, 110, 13754–13758.

    Article  CAS  PubMed  Google Scholar 

  40. C. Ma, M. G. Steinmetz, E. J. Kopatz, R. Rathore, Photochemical cleavage and release of carboxylic acids from α-keto amides, J. Org. Chem., 2005, 70, 4431–4442.

    Article  CAS  PubMed  Google Scholar 

  41. C. Ma, Y. Chen, M. G. Steinmetz, Photochemical cleavage and release of para-substituted phenols from α-keto amides, J. Org. Chem., 2006, 71, 4206–4215.

    Article  CAS  PubMed  Google Scholar 

  42. H. E. Zimmerman, Apparatus for quantitative and preparative photolysis. The Wisconsin black box, Mol. Photochem., 1971, 3, 281–292.

    CAS  Google Scholar 

  43. J. P. Perdew, K. Burke, M. Ernzerhof, Generalized gradient approximation made simple, Phys. Rev. Lett., 1996, 77, 3865–3868.

    Article  CAS  PubMed  Google Scholar 

  44. W. J. Hehre, L. Radom, P. v. R. Schleyer and J. A. Pople, Ab Initio Molecular Orbital Theory, John Wiley and Sons, New York, 1985.

    Google Scholar 

  45. G. Scalmani, M. J. Frisch, Continuous surface charge polarizable continuum models of solvation. I. General formalism, J. Chem. Phys., 2010, 132, 114110.

    Article  PubMed  CAS  Google Scholar 

  46. J. Tomasi, B. Mennucci, R. Cammi, Quantum mechanical continuum solvation models, Chem. Rev., 2005, 105, 2999.

    Article  CAS  PubMed  Google Scholar 

  47. J. Tomasi, B. Mennucci, E. Cancès, The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level, J. Mol. Struct. (Theochem), 1999, 464, 211.

    Article  CAS  Google Scholar 

  48. K. Fukui, The path of chemical reactions—the IRC approach, Acc. Chem. Res., 1981, 14, 363–368.

    Article  CAS  Google Scholar 

  49. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski and D. J. Fox, GAUSSIAN 09 (Revision B.01), Gaussian, Inc., Wallingford CT, 2009.

    Google Scholar 

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Authors and Affiliations

  1. Department of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, Wisconsin, 53201-1881, USA

    Majher I. Sarker, Tasnuva Shahrin, Mark G. Steinmetz & Qadir K. Timerghazin

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  1. Majher I. Sarker
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  2. Tasnuva Shahrin
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  3. Mark G. Steinmetz
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  4. Qadir K. Timerghazin
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Correspondence to Mark G. Steinmetz or Qadir K. Timerghazin.

Additional information

Electronic supplementary information (ESI) available: 1H-NMRCOSY for 26, and 27. 1H-NMRNOESY for 27. X-diffraction data for 30. Comparison 1H-NMR between 27 and 30. 1H-NMR for a mixture of 30 and 31. 1H-NMR and 13C NMR spectra of all synthesized compound. Stern–Volmer quenching 8 (LG− = Cl−) by piperylene. Computed structures in Fig. 3 and 4. CCDC XXXXXX. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c2pp25051a

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Sarker, M.I., Shahrin, T., Steinmetz, M.G. et al. Photochemical electrocyclic ring closure and leaving group expulsion from N-(9-oxothioxanthenyl)benzothiophene carboxamides. Photochem Photobiol Sci 12, 309–322 (2013). https://doi.org/10.1039/c2pp25051a

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