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The Role of Methoxy Group in the Nazarov Cyclization of 1,5-bis-(2-Methoxyphenyl)-1,4-Pentadien-3-one in the Gas Phase and Condensed Phase

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Journal of The American Society for Mass Spectrometry

Abstract

ESI-protonated 1,5-bis-(2-methoxyphenyl)-1,4-pentadien-3-one (1) undergoes a gas-phase Nazarov cyclization and dissociates via expulsions of ketene and anisole. The dissociations of the [M + D]+ ions are accompanied by limited HD scrambling that supports the proposed cyclization. Solution cyclization of 1 was effected to yield the cyclic ketone, 2,3-bis-(2-methoxyphenyl)-cyclopent-2-ene-1-one, (2) on a time scale that is significantly shorter than the time for cyclization of dibenzalacetone. The dissociation characteristics of the ESI-generated [M + H]+ ion of the synthetic cyclic ketone closely resemble those of 1, suggesting that gas-phase and solution cyclization products are the same. Additional mechanistic studies by density functional theory (DFT) methods of the gas-phase reaction reveals that the initial cyclization is followed by two sequential 1,2-aryl migrations that account for the observed structure of the cyclic product in the gas phase and solution. Furthermore, the DFT calculations show that the methoxy group serves as a catalyst for the proton migrations necessary for both cyclization and fragmentation after aryl migration. An isomer formed by moving the 2-methoxy to the 4-position requires relatively higher collision energy for the elimination of anisole, as is consistent with DFT calculations. Replacement of the 2-methoxy group with an OH shows that the cyclization followed by aryl migration and elimination of phenol occurs from the [M + H]+ ion at low energy similar to that for 1.

The role of methoxy group in the Nazarov cyclization of 1,5-bis-(2-methoxyphenyl)-1,4-pentadien-3-one in the gas-phase and condensed phase by June Cyriac, Justin Paulose, M. George, Department of Chemistry, Sacred Heart College, Thevara, Cochin, Kerala, India-682013., M. Ramesh, R. Srinivas, National center for Mass Spectrometry, IICT, Hyderabad, India. Daryl Giblin and Michael L. Gross, Department of Chemistry, Washington University in St.Louis, St.Louis, USA, MO 63130.

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Acknowledgments

The authors J.C., J.P., and M.G. thank the principal, Sacred Heart College, Thevara, for providing infrastructure. R.S. and V.R. thank Dr. J. S. Yadav, Director, IICT, Hyderabad, for facilities. Research at WU was supported by the National Centers for Research Resources of the NIH, NIGMS grant P41 GM103422-35, and by the Washington University Computational Chemistry Facility, supported by NSF grant CHE-0443501.

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Authors and Affiliations

  1. Department of Chemistry, Sacred Heart College, Thevara, Cochin, Kerala, India

    June Cyriac, Justin Paulose & Mathai George

  2. National Center for Mass Spectrometry, IICT, Hyderabad, India

    Marupaka Ramesh & Ragampeta Srinivas

  3. Department of Chemistry, Washington University in St. Louis, St. Louis, MO, 63130, USA

    Daryl Giblin & Michael L. Gross

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  1. June Cyriac
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Cyriac, J., Paulose, J., George, M. et al. The Role of Methoxy Group in the Nazarov Cyclization of 1,5-bis-(2-Methoxyphenyl)-1,4-Pentadien-3-one in the Gas Phase and Condensed Phase. J. Am. Soc. Mass Spectrom. 25, 398–409 (2014). https://doi.org/10.1007/s13361-013-0785-8

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