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A new treatment of chemical reactivity: Development of EROS, an expert system for reaction prediction and synthesis design

  • Johann Gasteiger
  • Michael G. Hutchings
  • Bernd Christoph
  • Leopold Gann
  • Christian Hiller
  • Peter Löw
  • Mario Marsili
  • Heinz Saller
  • Kazumi Yuki
Conference paper
Part of the Topics in Current Chemistry book series (TOPCURRCHEM, volume 137)

Abstract

An expert system for the prediction of the course of organic chemical reactions and for the design of organic syntheses has been built. It does not depend on a database of chemical reactions. Instead, the system generates reactions from first principles by formal bond- and electron-shifting processes. The reaction sites are found by application of quantitative models for the prediction of chemical reactivity. This approach is founded on procedures that allow rapid calculation of the various physicochemical effects that influence the course of chemical reactions. The extent to which these factors influence chemical reactivity has been studied by statistical methods. Examples of the prediction of quantitative data on chemical reactivity, and of the course of complex organic reactions, are described.

Keywords

Chemical Reactivity Inductive Effect Proton Affinity Resonance Effect Reactivity Function 
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.

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14 References

  1. 1.
    Corey, E. J., Dankeiser, R. L. Chandrasekaran, S., Keck, G. E., Gopalan, B., Larsen, S. D., Siret, P., Gras, J.-L.: J. Am. Chem. Soc. 100, 8034–8036 (1978)CrossRefGoogle Scholar
  2. 2.
    For a brief, enlightening discussion see: Turner, S.: The Design of Organic Syntheses, Elsevier, Amsterdam 1976Google Scholar
  3. 3.
    Corey, E. J.: Pure Appl. Chem. 14, 19–37 (1967)Google Scholar
  4. 4.
    Warren, S.: Organic Synthesis, The Disconnection Approach, Wiley, Chichester 1982Google Scholar
  5. 5.
    Gasteiger, J.: Chapter: Syntheseplanung, in: Computer in der Chemie, (Ziegler, E., Ed.), Springer, Heidelberg 1984, p. 207–257Google Scholar
  6. 6.
    Gasteiger, J., Jochum, C.: Topics Curr. Chem. 74, 93–126 (1978)Google Scholar
  7. 7. a)
    Gasteiger, J., Jochum, C., Marsili, M., Thoma, J.: Proceed. IVth Internat. Conf. on Computers in Chemical Research and Education, Novosibirsk, USSR 1978, p. 442–457Google Scholar
  8. 7. b)
    Gasteiger, J., Jochum, C., Marsili, M., Thoma, J.: Informal Commun. Math. Chem. 6, 177–199 (1979)Google Scholar
  9. 7. c)
    Gasteiger, J., Jochum, C., Marsili, M., Thoma, J.: Proceed. IVA-Symposium “The Use of Computers in Organic Chemistry”, Stockholm Sweden 1981, p. 51–68Google Scholar
  10. 7. d)
    Gasteiger, J., Marsili, M., Paulus, B.: in Data Processing in Chemistry, (Z. Hippe, Ed.) Elsevier, Amsterdam 1981, p. 229–246Google Scholar
  11. 7. e)
    Gasteiger, J.: Chim. Ind. (Milan) 64, 714–721 (1982)Google Scholar
  12. 7. f)
    Gasteiger, J., Christoph, B., Gann, L., Hutchings, M. G., Saller, H., Yuki, K.: Royal Soc. of Chem., Residential School “Computer-Aided Organic Synthesis Design and Molecular Graphics”, University of Leeds 1983Google Scholar
  13. 7. g)
    Marsili, M., Gasteiger, J., Carter, R. E.: Chimica Oggi, 1984, (9) 11–18Google Scholar
  14. 8.
    Dugundji, I., Ugi, I.: Topics Curr. Chem. 39, 19–64 (1973)Google Scholar
  15. 9.
    Ugi, I., Gillespie, P. D.: Angew. Chem. 83, 980–981; 982–985 (1971); Angew. Chem. Int. Ed. Engl. 10, 914, 915 (1971)Google Scholar
  16. 10.
    Hofmann, H. M. R. and Rabe, J.: Angew. Chem. 97, 96–112 (1985); Angew. Chem. Int. Edn. Engl. 24, 94–123 (1985)Google Scholar
  17. 11.
    Blair, J., Gasteiger, J., Gillespie, C., Gillespie, P. D., Ugi, I.: Tetrahedron 30, 1845–1859 (1974)CrossRefGoogle Scholar
  18. 12.
    Cahn, R. S., Ingold, C., Prelog, V.: Angew. Chem. 78, 413–447 (1966); Angew. Chem. Int. Ed. Engl. 5, 385–419 (1966)Google Scholar
  19. 12a.
    Prelog, V., Helmchen, G.: Angew. Chem. 94, 614–631 (1982); Angew. Chem. Int. Ed. Engl. 21, 567–584 (1982)Google Scholar
  20. 13.
    Jochum, C., Gasteiger, J.: J. Chem. Inf. Comput. Sci., 17, 113–117 (1977); ibid. 19, 49–50 (1979)CrossRefGoogle Scholar
  21. 14.
    Christoph, B.: unpublished resultsGoogle Scholar
  22. 15.
    Gasteiger, J., Jochum, C.: J. Chem. Inf. Comput. Sci. 19, 43–48 (1979)CrossRefGoogle Scholar
  23. 16.
    Bart, J. C. J., Garagnani, E.: Z. Naturforsch. 31b, 1646–1653 (1976); ibid. 32b, 455–464 (1977); ibid. 32b, 465–468 (1977); ibid 32b, 678–683 (1977)Google Scholar
  24. 17.
    Huisgen, R.: Angew. Chem. 75, 604–637 (1963); ibid. 75, 742–754 (1963)Google Scholar
  25. 18.
    Alper, H., Perera, C. P., Ahmed, F. R.: J. Am. Chem. Soc. 103, 1289–1291 (1981)CrossRefGoogle Scholar
  26. 19.
    Skakibara, T., Alper, H.: J. Chem. Soc. Chem. Commun. 1979, 458Google Scholar
  27. 20.
    Suckling, C. J., Suckling, K. E., Suckling, C. W.: Chemistry Through Models, Cambridge University Press, Cambridge 1978Google Scholar
  28. 21.
    Eigen, M.: The Physicist's Conception of Nature, quoted in “A Dictionary of Contemporary Quotations”, compiled by Green, J., Pan Books 1982Google Scholar
  29. 22.
    Cox, J. D., Pilcher, G.: Thermochemistry of Organic and Organometallic Compounds, Academic Press, London 1970Google Scholar
  30. 23.
    Caglioti, E., Marsili, M.: results presented at 7th Internat. Conf. on Computers in Chemical Research and Education, Garmisch-Partenkirchen, W. Germany 1985Google Scholar
  31. 24.
    Gasteiger, J.: Comput. Chem. 2, 85–88 (1978)Google Scholar
  32. 25.
    Gasteiger, J.: Tetrahedron 35, 1419–1426 (1979)Google Scholar
  33. 26.
    Allen, T. L.: J. Chem. Phys. 31, 1039–1049 (1959)Google Scholar
  34. 26a.
    Kalb, A. J., Chung, A. L. H., Allen, T. L.: J. Am. Chem. Soc. 88, 2938–2942 (1966)Google Scholar
  35. 27.
    Benson, S. W., Buss, J. H.: J. Chem. Phys. 29, 546–572 (1958)Google Scholar
  36. 27a.
    Benson, S. W.: Thermochemical Kinetics, 2nd Ed. Wiley, New York 1976Google Scholar
  37. 28.
    Gasteiger, J., Jacob, P., Strauss, U.: Tetrahedron 35, 139–146 (1979)Google Scholar
  38. 29.
    Gann, L., Löw, P., Sello, G., Yuki, K.: unpublished resultsGoogle Scholar
  39. 30.
    Gasteiger, J., Dammer, O.: Tetrahedron 34, 2939–2945 (1978)Google Scholar
  40. 31.
    Guthrie, J. P., Cullimore, P. A.: Can. J. Chem. 57, 240–248 (1979)Google Scholar
  41. 31a.
    Guthrie, J. P.: ibid. 57, 797–802 (1979)Google Scholar
  42. 32.
    Egger, K. W., Cocks, A. T.: Helv. Chim. Acta 56, 1516–1536 (1973)Google Scholar
  43. 33.
    McMillen, D. F., Golden, D. M.: Ann. Rev. Phys. Chem. 33, 493–532 (1982)Google Scholar
  44. 34.
    Chapman, N. B., Shorter, J.: Advances in Linear Free Energy Relationships, Plenum Press, London 1972Google Scholar
  45. 34a.
    Chapman, N. B., Shorter, J.: Correlation Analysis in Chemistry — Recent Advances, Plenum Press New York 1978Google Scholar
  46. 35.
    Mulliken, R. S.: J. Chem. Phys. 23, 1833–1840 (1955)CrossRefGoogle Scholar
  47. 36.
    Mulliken, R. S.: ibid, 2, 782–793 (1934)Google Scholar
  48. 37.
    Hinze, J., Jaffe, H. H.: J. Am. Chem. Soc. 84, 540–546 (1962); J. Phys. Chem. 67, 1501–1506 (1963)Google Scholar
  49. 37a.
    Hinze, J., Whitehead, M. A., Jaffe, H. H.: J. Am. Chem. Soc. 85, 148–154 (1963)Google Scholar
  50. 38.
    Sanderson, R. T.: Science 144, 670 (1964)Google Scholar
  51. 39.
    Huheey, J. E.: J. Phys. Chem. 69, 3284–3291 (1965); ibid. 70, 2086–2092 (1966)Google Scholar
  52. 40.
    Gasteiger, J., Marsili, M.: Tetrahedron Letters 1978, 3181–3184Google Scholar
  53. 41.
    Gasteiger, J., Marsili, M.: Tetrahedron 36, 3219–3228 (1980)Google Scholar
  54. 42.
    Guillen, M. D., Gasteiger, J.: ibid. 39, 1331–1335 (1983)Google Scholar
  55. 43.
    Mortier, W. J., Van Genechten, K., Gasteiger, J.: J. Am. Chem. Soc. 107, 829–835 (1985)Google Scholar
  56. 44.
    Gasteiger, J., Marsili, M.: Org. Magn. Resonance 15, 353–360 (1981)Google Scholar
  57. 45.
    Gasteiger, J., Guillen, M. D.: J. Chem. Res. (S) 1983, 304–305; (M) 1983, 2611–2624Google Scholar
  58. 46.
    Knorr, R., Saller, H., Gasteiger, J.: unpublished resultsGoogle Scholar
  59. 47.
    Marsili, M., Gasteiger, J.: Croat. Chem. Acta 53, 601–614 (1980)Google Scholar
  60. 48.
    Gasteiger, J., Saller, H.: Angew. Chem. 97, 699–701 (1985); Angew. Chem. Int. Ed. Engl. 24, 687–689 (1985)Google Scholar
  61. 49.
    Hutchings, M. G., Gasteiger, J.: Tetrahedron Lett. 24, 2541–2544 (1983)Google Scholar
  62. 50.
    Pauling, L.: The Nature of the Chemical Bond, 3rd Edit., Cornell University Press, Ithaca, N.Y. 1960, p. 88Google Scholar
  63. 51.
    Lias, S. G., Liebman, J. F., Levin, R. D.: J. Phys. Chem. Ref. Data 13, 695–808 (1984)Google Scholar
  64. 52.
    Saller, H.: Ph. D. thesis, TU München 1985Google Scholar
  65. 53.
    Gasteiger, J., Hutchings, M. G.: Tetrahedron Lett. 24, 2537–2540 (1983)Google Scholar
  66. 53a.
    Gasteiger, J., Hutchings, M. G.: J. Chem. Soc. Perkin II, 1984, 559–564Google Scholar
  67. 54.
    Gasteiger, J., Löw, P.: unpublished resultsGoogle Scholar
  68. 56.
    Gasteiger, J., Hutchings, M. G.: J. Am. Chem. Soc. 106, 6489–6495 (1984)Google Scholar
  69. 57.
    Wolf, J. F., Abboud, J. L. M., Taft, R. W.: J. Org. Chem. 42, 3316–3317 (1977)Google Scholar
  70. 58.
    Bordwell, F. G., Drucker, G. E., McCollum, G. J.: ibid. 47, 2504–2510 (1982)Google Scholar
  71. 59.
    Hutchings, M. G., Gasteiger, J.: J. Chem. Soc. Perkin 2, 1986, in pressGoogle Scholar
  72. 60.
    Hutchings, M. G., Gasteiger, J.: J. Chem. Soc. Perkin 2, 1986, in pressGoogle Scholar
  73. 61.
    Kreevoy, M. M., Taft, R. W., J. Am. Chem. Soc. 77, 5590–5595 (1955)Google Scholar
  74. 62.
    Fukui, K.: Fortschr. Chem. Forsch. 15, 1–85 (1970); Acc. Chem. Res. 4, 57–64 (1971)Google Scholar
  75. 63.
    Houk, K. N.: Topics Curr. Chem. 79, 1–40 (1979)Google Scholar
  76. 64.
    Burnier, J. S., Jorgensen, W. C.: J. Org. Chem. 49, 3001–3020 (1984)Google Scholar
  77. 65.
    Gasteiger, J., Hutchings, M. G., Saller, H.: unpublished resultsGoogle Scholar
  78. 66.
    Saller, H., Löw, P., Hutchings, M. G., Gasteiger, J.: results presented at the 7th Internat. Conf. on Computers in Chemical Research and Education, Garmisch-Partenkirchen, W. Germany 1985Google Scholar
  79. 66. a
    Gasteiger, J., Hutchings, M. G., Löw, P., Saller, H.: in: Artificial Intelligence Applications in Chemistry, ACS-Symposium Series, in pressGoogle Scholar
  80. 67.
    Snowden, R. L.: Helv. Chim. Acta 66, 1031–1038 (1985)Google Scholar
  81. 70.
    Meinwald, J., Labana, S. S., Chadha, M. S.: J. Am. Chem. Soc. 85, 582–585 (1963)Google Scholar
  82. 71.
    Rey, M., Dreiding, A. S.: Helv. Chim. Acta 48, 1985–1987 (1965)Google Scholar
  83. 72.
    Baxter, A. D., Roberts, S. M., Scheinmann, F., Wakefield, B. J., Newton, R. F.: J. Chem. Soc., Chem. Commun. 1983, 932–933Google Scholar
  84. 73.
    Ho, T. L., Stark, C. J.: Liebigs Ann. Chem. 1983, 1446–1447Google Scholar
  85. 74.
    Piancatelli, G., Scettri, A., David, G., D'Auria, M.: Tetrahedron 34, 2775–2778 (1978)Google Scholar
  86. 75.
    Dohgane, I., Yamachika, H., Minai, M.: J. Synth. Org. Chem. (Japan) 1984, 896–903Google Scholar
  87. 76.
    Bertz, S. H.: J. Am. Chem. Soc. 103, 3599–3601 (1981); ibid. 104, 5801–5803 (1982)Google Scholar
  88. 77.
    Hiller, C., Christoph, B., Gann, L., Gasteiger, J.: results presented at 7th Internat. Conf. on Computers in Chemical Research and Education, Garmisch-Partenkirchen, W. Germany 1985Google Scholar
  89. 78.
    Michie, D., Johnston, R.: The Creative Computer, Pelican Books, England 1985Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • Johann Gasteiger
    • 1
  • Michael G. Hutchings
    • 1
  • Bernd Christoph
    • 1
  • Leopold Gann
    • 1
  • Christian Hiller
    • 1
  • Peter Löw
    • 1
  • Mario Marsili
    • 1
  • Heinz Saller
    • 1
  • Kazumi Yuki
    • 1
  1. 1.Organisch-Chemisches InstitutTechnische Universität MünchenGarchingFRG

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