Polar [4+2+] diels-alder cycloaddition to nitrilium and immonium ions in the gas phase: Applications of multiple stage mass spectrometry in a pentaquadrupole instrument

  • Marcos N. Eberlin
  • Nelson H. Morgon
  • Sheng S. Yang
  • Brian J. Shay
  • R. Graham Cooks


Multiple stage MS2 and MS3 mass spectrometric experiments, performed using a pentaquadrupole instrument, are employed to explore the gas-phase ion-molecule chemistry of several nitrilium [R-C≡N+-H (1), R-C≡N+-CH3 (2), and H-C≡N+-C2H5 (3)] as well as immonium ions RR1C=N+R2R3 (4) with the neutral diene isoprene. Polar [4+2+] Diels-Alder cycloaddition is observed for nitrilium ions when the energy gap between the lowest unoccupied molecular orbital (LUMO) of the ion and the highest occupied molecular orbital (HOMO) of the isoprene is small and the competing proton transfer reaction is endothermic. Thus, C-protonated methyl isonitrile H-C≡N+-CH3 (2a) and its higher homolog H-C≡N+-C2H5 (3a) form abundant [4+2+] cycloadducts with isoprene, but several protonated nitriles 1 do not; instead they show exothermic proton transfer as the main ion-molecule reaction. Replacement of the methyne hydrogen in 2a by a methyl, ethyl, or phenyl group (2b–d) raises the LUMO-HOMO gap, which greatly decreases the total yield of ion-molecule products and precludes cycloaddition. On the other hand, the electron-withdrawing acetyl and bromine substituents in 2e and 2f substantially lower the LUMO energy of the ions and cycloaddition reaction occurs readily. The simplest member of the immonium ion series, CH2=NH 2 + (4a), reacts readily by cycloaddition, whereas alkyl substitution on either the carbon or nitrogen (4b–f) dramatically lowers the overall reactivity, which substantially decreases or even precludes cycloaddition. In strong contrast, the N-phenyl (4g) and N-acetyl (4h) ions and the N-vinyl-substituted immonium ion, N-protonated 2-aza-butadiene (4i), react extensively with isoprene, mainly by [4+2+] cycloaddition. However, the isomeric C-vinyl-substituted ion (4j) displays only modest reactivity in both the proton-transfer and the cycloaddition channels.

Collision-induced dissociation (CID) of the cycloadducts performed by on-line MS3 experiments demonstrates that they are covalently bound and supports their assignments as cycloaddition products. Retro Diels-Alder fragmentation is a major process for cycloadducts of both the immonium and the nitrilium ions, but other fragmentation processes also are observed. The cycloadduct of 4a with butadiene displays CID fragmentation identical to that of the authentic ion produced by protonation of 1,2,3,6-tetrahydropyridine, which thus strengthens the [4+2+] cycloaddition proposal. AM1 calculations also support the formation of the [4+2+] cycloadducts, which are shown in several cases to be much more stable than the products of simple addition, that is, the ring-open isomers.


Proton Transfer High Occupied Molecular Orbital Lower Unoccupied Molecular Orbital Isoprene Lower Unoccupied Molecular Orbital 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Thomson, J J Rays of Positive Electricity and their Application to Chemical Analysis, Longmans, Green and Co.: New York, 1913 (2nd ed. 1921).Google Scholar
  2. 2.
    Dempster, A J. Phil Mag 1916, 31, 438.Google Scholar
  3. 3.
    Smith, H D Rev. Mod Phys 1931, 3, 347CrossRefGoogle Scholar
  4. 4.
    Eyring, H, Hirschfelder, J O, Taylor, H. S. J Chem Phys 1936, 4, 479CrossRefGoogle Scholar
  5. 5(a).
    Bowers, M T, Ed Gas Phase Ion Chemistry, Academic New York, 1979, Vol. 2,Google Scholar
  6. 5(b).
    Futrell, J H, Ed. Gaseous Ion Chemistry and Mass Spectrometry, Wiley New York, 1986,Google Scholar
  7. 5(c).
    Lias, S G, Ausloos, P, Eds Ion-Molecule Reactions, Their Role in Radiation Chemistry, American Chemical Society Washington, DC, 1975,Google Scholar
  8. 5(d).
    Franklin, J L, Ed Ion-Molecule Reactzons, Plenum New York, 1972,Google Scholar
  9. 5(e).
    Harrison, A G Chemical lomzation Mass Spectrometry, CRC Press Boca Raton, FL, 1983.Google Scholar
  10. 6.
    See, for example (a) J Phys. Chem Ref. Data 1990, 19, 1626, for a listing of rate constant references for the period 1982–1990;Google Scholar
  11. 6(b).
    Sieck, L W, Lias, S G Rate Coefficients for Ion-Molecule Reactions I Ions Contaming C and H, J Phys Chem Ref. Data 1976, 5, 1123,CrossRefGoogle Scholar
  12. 6(c).
    Sieck, L W Rate Coefficients for Ion-Molecule Reactions. Organic Ions other Than Those Containing C and H; NSRDS-NBS 64, National Bureau of Standards, Washington, DC, 1979Google Scholar
  13. 7.
    Meot-ner (Mautner), M. In Gas Phase Ion Chemistry; Bowers, M T, Ed, Academic New York, 1979, Vol 2Google Scholar
  14. 8(a).
    Mallard, W G NIST Positive Ion Energetics Database 19A, version 1.1, 1989, distributed by Standard Reference Data, NIST, Gaithersburg, MD 20899,Google Scholar
  15. 8(b).
    Lias, S. G, Bartmess, J E, Liebman, J. F., Holmes, J L, Levin, R D, Mallard, W G J Phys Chem Ref Data 1988, 17 (Supp. 1),Google Scholar
  16. 8(c).
    Lias, S. G, Liebman, J F, Levin, R D J. Phys Chem Ref Data 1984, 13, 695CrossRefGoogle Scholar
  17. 9(a).
    Munson, M S B J Am Chem Soc 1965, 87, 2332,CrossRefGoogle Scholar
  18. 9(b).
    Brauman, I I, Riveros, J. M, Blair, L K J Am. Chem. Soc. 1971, 93, 3914,CrossRefGoogle Scholar
  19. 9(c).
    Ho, Y., Squires, R R J Am Chem. Soc. 1992, 114, 10961CrossRefGoogle Scholar
  20. 10(a).
    Adams, N. G, Smith, D Flowing Afterglow and SIFT. In Techmques for the Study of Ion-Molecule Reactions, Farrar, J M, Saunders, W. H, Jr, Eds, Wiley-Interscience New York, 1988, Chap 4;Google Scholar
  21. 10(b).
    Graul, S T, Squires, R R Mass Spectrom Rev 1988, 7, 263.CrossRefGoogle Scholar
  22. 11.
    Jalonen, J J Chem. Soc Chem. Commun 1985, 872Google Scholar
  23. 12(a).
    Beaugrand, C, Jaouen, D., Mestdagh, H, Rolando, C Anal Chem 1989, 61, 1447,CrossRefGoogle Scholar
  24. 12(b).
    Kenttamaa, H I; Pachuta, R. R, Rothwell, A. P, Cooks, R. G J. Am Chem. Soc 1989, 111, 1654,CrossRefGoogle Scholar
  25. 12(c).
    Dolnikowski, G G.; Kristo, M. J, Enke, C G.; Watson, J. T. Int. J. Mass Spectrom. Ion Processes 1988, 82, 1,CrossRefGoogle Scholar
  26. 12(d).
    Kinter, M T., Bursey, M M J. Ant Chem. Soc 1986, 108, 1797,CrossRefGoogle Scholar
  27. 12(e).
    Yost, R. A.; Fetterolf, D D. Mass Spectrom. Rev 1983, 2, 1.CrossRefGoogle Scholar
  28. 13(a).
    Nourse, B D, Cooks, R. G. Anal. Chim. Acta 1990, 228, 1,CrossRefGoogle Scholar
  29. 13(b).
    Nibbering, N. M. M. Acc. Chem. Res. 1990, 23, 279,CrossRefGoogle Scholar
  30. 13(c).
    Wilkins, C. L., Choudhury, A. K, Nuwaysir, L. M, Gross, M. L Mass Spectrom. Rev. 1989, 8, 67,CrossRefGoogle Scholar
  31. 13(d).
    Buchanan, M V, Ed., Fourier Transform Mass Spectrometry. Evolution, Innovation, and Applications, ACS Symposium Series 359, American Chemical Soaety Washington, DC, 1988, pp 1–205,Google Scholar
  32. 13(e).
    Kemper, P. R.; Bowers, M. T. Ion Cyclotron Resonance Spectrometry. In Techniques for the Study of Ion-Molecule Reacttons, Farrar, J M., Saunders, W H, Eds., Wiley-Interscience New York, 1988; Chap 1;Google Scholar
  33. 13(f).
    Freiser, B S. Fourier Transform Mass Spectrometry. In Techniques for the Study of Ion-Molecule Reactions; Farrar, J M, Saunders, W H, Eds., Wiley-interscience New York, 1988, Chap 2Google Scholar
  34. 14.(a)
    Busch, K. L, Glish, G L, McLuckey, S A Mass Spectrometry/Mass Spectrometry Techniques and Applications of Tandem Mass Spectrometry, VCH New York, 1988,Google Scholar
  35. 14(b).
    Usypchuk, L L. Harrison, A G, Wang, J Y. Org Mass Spectrom 1992, 27, 777CrossRefGoogle Scholar
  36. 15(a).
    Morrison, J D., Staanney, D A, Tedder, J Proceedings of the 34th American Society of Mass Spectrometry Conference on Mass Spectrometry and Allied Topics, Cincinnati, OH, 1986, p 222,Google Scholar
  37. 15(b).
    Mestdagh, H, Morin, N, Rolando, C ; Beaugrand, C., DeMaack, F. Proceedings of the 34th American Society of Mass Spectrometry Conference on Mass Sepctrometry and Allied Topics, Cincinnati OH, 1986, p 799Google Scholar
  38. 15(c).
    Schwartz, J C, Schey, K L, Cooks, R G Int J Mass Spectrom Ion Processes 1990, 101, 1CrossRefGoogle Scholar
  39. 16.
    Schwartz, J. C., Wade, A.P, Enke, C G, Cooks, R G Anal. Chem 1990, 62, 1809CrossRefGoogle Scholar
  40. 17.
    Boger, D. L, Weinreb, S. N. In Hetero Dtels-Alder Methodology in Organic Synthesis; Wasserman, H H, Ed., Academic New York, 1987, Fringuelli, F, Taticchi, A., Eds Dienes in the Diels-Alder Reaction, Wiley New York, 1990Google Scholar
  41. 18.
    Schmidt, R. R Angew. Chem Int Ed 1973, 12, 212CrossRefGoogle Scholar
  42. 19.(a)
    Gassman, P G, Singleton, D. A, Wilwerding, J J, Chavan, S. P J. Ant. Chem. Soc 1987, 109, 2182,CrossRefGoogle Scholar
  43. 19(b).
    Gassman, P G, Singleton, D. A, J Ant. Chem. Soc. 1984, 106, 7993CrossRefGoogle Scholar
  44. 20(a).
    Kim, T., Pye, R. J, Bauld, N. L. J. Am. Chem Soc 1990, 112, 6285,CrossRefGoogle Scholar
  45. 20(b).
    Bauld, N. L, Bellville, D. J; Harirchian, B., Lorenz, K T ; Pabon, R A, Jr.; Reynolds, D.W., Wirth, D D, Chiou, H.-S.; Marsh, B K Acc. Chem. Res 1987, 20, 371,CrossRefGoogle Scholar
  46. 20(c).
    Bellville, D J., Wirth, D. D, Bauld, N L. J Am. Chem Soc 1981, 103, 718CrossRefGoogle Scholar
  47. 21.(a)
    Shay, B. J, Eberlin, M N Cooks, R G, Wesdemiotis, C J Ant Soc Mass Spectrom. 1992, 3, 518,CrossRefGoogle Scholar
  48. 21.(b)
    Eberlin, M N, Majumdar, T K., Cooks, R. G. J Am Chem. Soc. 1992, 114, 2884,CrossRefGoogle Scholar
  49. 21(c).
    Eberlin, M N, Cooks, R. G J Am Chem Soc 1993, 115, 9226.CrossRefGoogle Scholar
  50. 22(a).
    Wilkins, C L, Gross, M L J Am Chem. Soc 1971, 93, 895;CrossRefGoogle Scholar
  51. 22(b).
    van Doorn, R, Nibbering, N M M, Ferrer-Correia, A J V., Jennings, K. R. Org. Mass Spectrom 1978, 13, 729;CrossRefGoogle Scholar
  52. 22(c).
    Castle, L W, Gross, M L Org Mass Spectrom 1989, 24, 637,CrossRefGoogle Scholar
  53. 22(d).
    Groenewold, G S, Gross, M L. J. Am Chem. Soc 1984, 106, 6575,CrossRefGoogle Scholar
  54. 22(e).
    Groenewold, G S, Gross, M L J Ant. Chem Soc 1984, 106, 6569CrossRefGoogle Scholar
  55. 23(a).
    McEwan, M. J, Anicich, V. G, Huntress, W T, Kemper, P R, Bowers, M T Chem Phys Lett 1980, 75, 278,CrossRefGoogle Scholar
  56. 23(b).
    Bass, L M, Kemper, P R, Anicich, V G, Bowers, M T J Am Chem Soc. 1981, 103, 5283,CrossRefGoogle Scholar
  57. 23(c).
    Gilbert, R G, McEwan, M J. Aust J Chem 1985, 38, 231,CrossRefGoogle Scholar
  58. 23(d).
    Iraqi, M, Lifshitz, C Int J Mass Spectrom Ion Processes 1986, 71, 245CrossRefGoogle Scholar
  59. 24.
    Wincel, H, Fokkens, R H, Nibbering, N M M Int J Mass Spectrom. Ion Processes 1989, 91, 339CrossRefGoogle Scholar
  60. 25(a).
    Illies, A J, Liu, S., Bowers, M. T. J. Am Chem Soc 1981, 103, 5674,CrossRefGoogle Scholar
  61. 25(b).
    Wurtwein, E.-U J Org Chem 1984, 49, 2971,CrossRefGoogle Scholar
  62. 25(b).
    Nguyen, M T, Ha, T K J Chem Soc Perkin Trans II 1984, 1401,Google Scholar
  63. 25(c).
    Bonnett-Delpon, D, Charpenher-Morize, M. Chem Phys Left. 1985, 116, 478,CrossRefGoogle Scholar
  64. 25(d).
    Meot-Ner (Mautner), M, Karpas, Z, Deakyne, C A J Ant Chem Soc 1986, 108, 3913,CrossRefGoogle Scholar
  65. 25(e).
    Deakyne, C A., Meot-Ner (Mautner), M J. Phys Chem 1990, 94, 232,CrossRefGoogle Scholar
  66. 25(f).
    Wincel, H, Fokkens, R H, Nibbering, N M M Int J Mass Spectrom Ion Processes 1989, 88, 241,CrossRefGoogle Scholar
  67. 25(g).
    Knight, J S, Freeman, C. G, McEwan, M J J Am Chem Soc 1986, 108, 1404CrossRefGoogle Scholar
  68. 25(h).
    Bouchoux, G, Flament, J P, Hoppilliard, Y., Tortajada, J, Flammang, R, Maquestiau, A J Am Chem Soc 1989, 111, 5560CrossRefGoogle Scholar
  69. 26.
    Fleming, I Frontier Orbitals and Organic Chemical Reactions, Wiley New York, 1977Google Scholar
  70. 27.
    Dewar, M J S, Zoebisch, E G, Healy, E F, Stewart, J J P J Am Chem. Soc. 1985, 107, 3902,CrossRefGoogle Scholar
  71. 28.
    Porter, Q N Mass Spectrometry of Heterocychc Compounds, Taylor, E. C, Weissberger, A, Eds., Wiley-Interscience New York, 1985Google Scholar
  72. 29.
    Stewart, J J P MOPAC A General Molecular Orbital Package, Quantum Chemistry Program Exchange (QCPE) 455, version 6Google Scholar
  73. 30.
    Boy, D. B., Smith, D W, Stewart, J J P, Wimmer, E J Comp Chem 1988, 9, 387.CrossRefGoogle Scholar
  74. 31.
    Sustmann, R, Schubert, R Angew Chem Int Ed. 1972, 11, 840.CrossRefGoogle Scholar
  75. 32.
    Cooks, R. G, Kruger, T L. J Am Chem Soc. 1977, 99, 1279CrossRefGoogle Scholar

Copyright information

© American Society for Mass Spectrometry 1995

Authors and Affiliations

  • Marcos N. Eberlin
    • 1
  • Nelson H. Morgon
    • 1
  • Sheng S. Yang
    • 2
  • Brian J. Shay
    • 2
  • R. Graham Cooks
    • 2
  1. 1.Umversldade Estadual de CampinasInstituto de QuímicaCampinas, SPBrazil
  2. 2.Department of ChemistryPurdue UniversityWest Lafayette

Personalised recommendations