Meerwein reaction of phosphonium ions with epoxides and thioepoxides in the gas phase

  • Eduardo C. Meurer
  • Hao Chen
  • Leah S. Riter
  • R. Graham Cooks
  • Marcos N. Eberlin


Phosphonium ions are shown to undergo a gas-phase Meerwein reaction in which epoxides (or thioepoxides) undergo three-to-five-membered ring expansion to yield dioxaphospholanium (or oxathiophospholanium) ion products. When the association reaction is followed by collision-induced dissociation (CID), the oxirane (or thiirane) is eliminated, making this ion molecule reaction/CID sequence a good method of net oxygen-by-sulfur replacement in the phosphonium ions. This replacement results in a characteristic mass shift of 16 units and provides evidence for the cyclic nature of the gas-phase Meerwein product ions, while improving selectivity for phosphonium ion detection. This reaction sequence also constitutes a gas-phase route to convert phosphonium ions into their sulfur analogs. Phosphonium and related ions are important targets since they are commonly and readily formed in mass spectrometric analysis upon dissociative electron ionization of organophosphorous esters. The Meerwein reaction should provide a new and very useful method of recognizing compounds that yield these ions, which includes a number of chemical warfare agents. The Meerwein reaction proceeds by phosphonium ion addition to the sulfur or oxygen center, followed by intramolecular nucleophilic attack with ring expansion to yield the 1,3,2-dioxaphospholanium or 1,3,2-oxathiophospholanium ion. Product ion structures were investigated by CID tandem mass spectrometry (MS2) experiments and corroborated by DFT/HF calculations.


Propylene Oxide DMMP Chemical Warfare Agent Thiirane Cyclic Acetal 


  1. 1.
    Zerda, A. S.; Lesser, A. J. Organophosphorous Additive for Fortification, Processibility, and Flame Retardance of Epoxy Resins. J. Appl. Pol. Sci. 2002, 84(2), 302–309.CrossRefGoogle Scholar
  2. 2.
    Costa, L. G.; Cole, T. B.; Furlong, C. E. Polymorphisms of Paraoxonase (PON1) and their Significance in Clinical Toxicology of Organophosphates. J. Tox. 2003, 41(1), 37–45.Google Scholar
  3. 3.
    Aue, W. P.; Buchs, R.; Dutoit, J. C.; Siegenthaler, P.; Niederhauser, A. Analysis of Chemical Warfare Agents at the Nuclear Chemical (NC) Laboratory Spiez, Switzerland. Chimia 1997, 51(10), 684–685.Google Scholar
  4. 4.
    Weimaster, J. F.; Beaudry, W. T.; Bossle, P. C.; Ellzy, M. W.; Janes, L. G.; Johnson, D. W.; Lochner, J. M.; Pleva, S. G.; Reeder, J. H.; Rohrbaugh, D. K.; Rosso, T. E.; Szafraniec, L. J.; Szafraniec, L. L.; Albro, T. G.; Creasy, W. R.; Stuff, J. R.; Smith, P. B.; Stewart, I. R. Chemical Analysis of Environmental Samples Collected in Iraq: Analysis for the Presence of Chemical Warfare Agents. J. Chem. Tech. Biotech. 1995, 64(2), 115–128.CrossRefGoogle Scholar
  5. 5.
    Chen, H.; Zheng, X.; Cooks, R. G. Ketalization of Phosphonium Ions by 1,4-Dioxane: Selective Detection of the Chemical Warfare Agent Simulant DMMP in Mixtures Using Ion/Molecule Reactions. J. Am. Soc. Mass Spectrom. 2002, 14(3), 182–188.CrossRefGoogle Scholar
  6. 6.
    Wang, F.; Ma, S.; Tao, W. A.; Cooks, R. G. Replacement of C-O by P-O in Cyclic Acetals and Ketals. Angew. Chem. Int. Ed. 1999, 38(3), 386–389.CrossRefGoogle Scholar
  7. 7.
    Wang, F.; Tao, W. A.; Gozzo, F. C.; Eberlin, M. N.; Cooks, R. G. Synthesis of B- and P-Heterocycles by Reaction of Cyclic Acetals and Ketals with Borinium and Phosphonium Ions. J. Org. Chem. 1999, 64(9), 3213–3223.CrossRefGoogle Scholar
  8. 8.
    Leclerc, E.; Buchmann, W.; Taphanel, M.; Morizur, J. Gas-Phase Ion/Molecule Reactions Between Dimethoxyphosphonium Ions and Aromatic Hydrocarbons. Rapid Commun. Mass Spectrom. 2002, 16(7), 686–695.CrossRefGoogle Scholar
  9. 9.
    Gevrey, S.; Luna, A.; Taphanel, M.-H.; Tortajada, J.; Morizur, J.-P. Experimental and Theoretical Studies of the Gas-Phase Reactivity of the (HO)2P:O+ Phosphonium Ions Towards Methanol. Int. J. Mass Spectrom. 2002, 195/196, 545–563.Google Scholar
  10. 10.
    Leclerc, E.; Taphanel, M.; Morizur, J. Gas-Phase Reactivity of the O:P(OCH3)2+ Phosphonium Ion with Aliphatic Esters in a Quadrupole Ion Trap. Spontaneous Elimination of Ketenes. J. Mass Spectrom. 2002, 37(9), 903–909.CrossRefGoogle Scholar
  11. 11.
    Eberlin, M. N.; Majumdar, T. K.; Cooks, R. G. Structures and Mechanisms of Reactions of Isomeric C2H3O+ and C2H3S+ Ions Revealed through Ion/Molecule Reactions in Conjunction With 2D- and 3D Mass Spectrometry. J. Am. Chem. Soc. 1992, 114(8), 2884–2896.CrossRefGoogle Scholar
  12. 12.
    Eberlin, M. N.; Cooks, R. G. Polar [4 + 2+] Diels-Alder Cycloadditions of Acylium Ions in the Gas Phase. J. Am. Chem. Soc. 1993, 115(20), 9226–9233.CrossRefGoogle Scholar
  13. 13.
    Moraes, L. A. B.; Pimpim, R. S.; Eberlin, M. N. Novel Ketalization Reaction of Acylium Ions with Diols and Analogues in the Gas Phase. J. Org. Chem. 1996, 61, 8726.CrossRefGoogle Scholar
  14. 14.
    Moares, L. A. B.; Eberlin, M. N. Ketalization of Gaseous Acylium Ions. J. Am. Chem. Soc. 2001, 12, 150.Google Scholar
  15. 15.
    Eberlin, M. N.; Cooks, R. G. Gas Phase Oxirane Addition to Acylium Ions on Reactions with 1,3-Dioxolanes Elucidated by Tandem and Triple Stage Mass Spectrometric Experiments. Org. Mass Spectrom. 1993, 28, 679.CrossRefGoogle Scholar
  16. 16.
    Moraes, L. A. B.; Gozzo, F. C.; Eberlin, M. N.; Vainiotalo, P. Transacetalization with Acylium Ions: A Structurally Diagnostic Ion-Molecule Reaction for Cyclic Acetals and Ketals in the Gas Phase. J. Org. Chem. 1997, 62, 5096.CrossRefGoogle Scholar
  17. 17.
    Carvalho, M. C.; Juliano, V. F.; Kascheres, C.; Eberlin, M. N. Gas Phase Chemistry of the Heterocumulene Cations O=C=N+=C=O and O=C=C=N+=O. J. Chem. Soc. Perkin Trans. 1997, 2, 2347.Google Scholar
  18. 18.
    Moraes, L. A. B.; Eberlin, M. N. Dehydrobenzoyl Cations: Distonic Ions with Dual Free Radical and Acylium Ion Reactivity. J. Am. Chem. Soc. 1998, 120, 11136.CrossRefGoogle Scholar
  19. 19.
    Sparrapan, R.; Mendes, M. A.; Eberlin, M. N. Double Transacetalization of Diacylium Ions. J. Mass Spectrom. 2000, 35, 189.CrossRefGoogle Scholar
  20. 20.
    Moraes, L. A. B.; Mendes, M. A.; Sparrapan, R.; Eberlin, M. N. Transacetalization with Gaseous Carboxonium and Carbosulfonium Ions. J. Am. Soc. Mass Spectrom. 2001, 12, 14.CrossRefGoogle Scholar
  21. 21.
    Moares, L. A. B.; Kotiaho, T.; Eberlin, M. N. Gas-Phase Chemistry of Acylium Ions. Seven-to- Five Ring Contraction of 1,3-Dioxepane and 1,3-Dioxep-5-ene. J. Mass Spectrom. 1999, 34, 670.CrossRefGoogle Scholar
  22. 22.
    Meurer, E. C.; Moares, L. A. B.; Eberlin, M. N. Cyclization of Acylium Ions with Nitriles: Gas-Phase Synthesis and Characterization of 1,3,5-Oxadiazinium Ions. Int. J. Mass Spectrom. Ion Processes 2001, 212, 445.Google Scholar
  23. 23.
    Moraes, L. A. B.; Eberlin, M. N. The Gas-Phase Meerwein Reaction. Chem. Eur. J. 2002, 6, 897.CrossRefGoogle Scholar
  24. 24.
    Grandinetti, F.; Pepi, F.; Ricci, A. Ionic Fluorination of Carbon Monoxide as a Route to Gas-Phase Carbonylation of Inert C-H and N-H Bonds. Chem. Eur. J. 1996, 2, 495.CrossRefGoogle Scholar
  25. 25.
    Rocha, L. L.; Sparrapan, R.; Eberlin M. N. Reactions of Gaseous Halocarbonyl Cations with Aromatic Compounds: Ionic Carbonylation of Inert C-H Bonds. Int. J. Mass Spectrom. 2003, 228, 901.CrossRefGoogle Scholar
  26. 26.
    Reid, G. E.; Tichy, S. E.; Perez, J.; O’Hair, R. A. J.; Simpson, R. J.; Kenttamaa, H. I. N-Terminal Derivatization and Fragmentation of Neutral Peptides via Ion-Molecule Reactions with Acylium Ions: Toward Gas-Phase Edman Degradation? J. Am. Chem. Soc. 2001, 123, 1184.CrossRefGoogle Scholar
  27. 27.
    Bruins, A. P.; Nibbering, N. M. M. Ion Cyclotron Resonance Study on Benzoylation Reactions in the Gas-Phase. Tetrahedron Let. 1975, 50, 4491.CrossRefGoogle Scholar
  28. 28.
    Williamson, B. L.; Creaser, C. S. Ion-Molecule Reactions of the Benzoyl Ion [C6H5CO]+ with Compounds Containing the Amine Functional Group in a Quadrupole Ion Trap. Eur. Mass Spectrom. 1998, 4, 103.CrossRefGoogle Scholar
  29. 29.
    Moraes, L. A. B.; Eberlin, M. N. Structurally Diagnostic Ion-Molecule Reactions: Acylium Ions with α, β, and γ-Hydroxy Ketones. J. Mass Spectrom. 2002, 37, 162–168.CrossRefGoogle Scholar
  30. 30.
    Meurer, E. C.; Eberlin, M. N. Mono and Double Polar [4+2+] Diels-Alder Cycloaddition of Acylium Ions with O-Heterodienes. J. Mass Spectrom. 2002, 37, 146–154.CrossRefGoogle Scholar
  31. 31.
    Meurer, E. C.; Sabino, A. S.; Eberlin, M. N. Ionic Transacetalization with Acylium Ions: A Class-Selective and Structurally Diagnostic Reaction for Cyclic Acetals Performed under Unique Electrospray and Atmospheric Pressure Chemical Ionization In-Source Ion-Molecule Reaction Conditions. Anal. Chem. 2003, 75(17), 4701–4709.CrossRefGoogle Scholar
  32. 32.
    Meerwein, H. Organic Ionic Reactions. Angew. Chem. Int. Ed. 1955, 67(14/15), 374–380.Google Scholar
  33. 33.
    Gronert, S.; O’Hair, R. A. J.; Prodnuk, S.; Siilzle, D.; Robert, D. I.; DePuy, C. H. Gas-Phase Chemistry of the Silaformyl Anion, HSiO. J. Am. Chem. Soc. 1990, 112, 997.CrossRefGoogle Scholar
  34. 34.
    O’Hair, R. A. J.; Sheldon, J. C.; Bowie, J. H.; Damrauer, R.; DePuy, C. H. Gas-Phase Ion Chemistry of Siloxide and Silamide Ions by Using the Flowing Afterglow. Unusual Rearrangements Involving SiO and SiS Bond Formation. Aust. J. Chem. 1989, 42, 489.CrossRefGoogle Scholar
  35. 35.
    Thoen, K. K.; Gao, L.; Ranatunga, T. D.; Vainiotalo, P.; Kenttämaa, H. I. Stereoselective Chemical Ionization Mass Spectrometry: Reactions of CH3OPOCH3+ with Cyclic Vicinal Diols. J. Org. Chem. 1997, 62, 8702.CrossRefGoogle Scholar
  36. 36.
    Eberlin, M. N.; Cooks, R. G. Gas Phase Oxirane Addition to Acylium Ions on Reactions with 1,3-Dioxolanes Elucidated by Tandem and Triple Stage Mass Spectrometric Experiments. Org. Mass Spectrom. 1993, 28, 679.CrossRefGoogle Scholar
  37. 37.
    Becke, A. D. Density-Functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648.CrossRefGoogle Scholar
  38. 38.
    Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields. J. Phys. Chem. 1994, 98, 11623.CrossRefGoogle Scholar
  39. 39.
    Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density. Phys. Rev. B 1988, 37, 785.CrossRefGoogle Scholar
  40. 40.
    Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K. J. B.; Foresman, J.; Cioslowski, J. V.; Ortiz, B.; Stefanov, B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.6; Gaussian: Pittsburgh, PA, 1998Google Scholar
  41. 41.
    Bell, A. J.; Despyroux, D.; Watts, J. M. P. Fragmentation and Reactions of Organophosphate Ions Produced by Electrospray Ionization. Int. J. Mass Spectrom. Ion Processes 1997, 165/166, 533.CrossRefGoogle Scholar
  42. 42.
    Schwarz, J. C.; Wade, A. P.; Enke, C. G.; Cooks, R. G. Systematic Delineation of Scan Modes in Multidimensional Mass Spectrometry. Anal. Chem. 1990, 62, 1809–1818.CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 2004

Authors and Affiliations

  • Eduardo C. Meurer
    • 1
  • Hao Chen
    • 1
  • Leah S. Riter
    • 1
  • R. Graham Cooks
    • 1
  • Marcos N. Eberlin
    • 2
  1. 1.Department of ChemistryPurdue UniversityWest LafayetteUSA
  2. 2.Institute of ChemistryState University of Campinas, UNICAMP, SPBrazil

Personalised recommendations