Synthesis of some N-methyl-1,2,3,4-tetrahydroisoquinolines by Friedel–Crafts cyclisation using benzotriazole auxiliary

Abstract

1-Hydroxymethylbenzotriazole reacts with phenylethylamines to give the respective N,N-bis(benzotriazol-1-ylmethyl)phenylethylamines, which are then subject to an intramolecular Friedel–Crafts cyclisation at room temperature to yield N-benzotriazol-1-ylmethyl-1,2,3,4-tetrahydroisoquinolines. These crystalline UV- and oxygen-stable products can be reduced at room temperature to the corresponding N-methyl-1,2,3,4-tetrahydroisoquinolines using NaBH₄. The method offers an elegant approach to a wide range of N-methylated 1,2,3,4-tetrahydroisoquinolines since it can be applied not only for the synthesis of 1,2,3,4-tetrahydroisoquinolines with electron-donating substituents on the aromatic moiety, but also for deactivated derivatives. All steps involved work under very mild conditions in high to excellent yields.

References

1. K. W. Bentley, The Isoquinoline Alkaloids, Harwood Academic Publishers, Amsterdam, 1998.
2. Isoquinolines, ed. F. G. Kathawala, G. M. Coppola and H. F. Schuster, Wiley, New York, 1990.
3. M. Shamma, The Isoquinoline Alkaloids: Chemistry and Pharmacology, Academic Press, New York, 1972.
4. K. S. P. Mcnaught, C. Altomare, S. Cellamare, A. Carotti, U. Thull, P. A. Carrupt, B. Testa, P. Jenner and C. D. Marsden, Neuro Report, 1995, 6, 1105.
5. T. Fukuda, Brain Res., 1994, 639, 325.
6. H. Rollema, E. A. Johnson, R. G. Booth, P. Caldera, P. Lampen, S. K. Youngster, A. J. Trevor, N. Naiman and N. Castagnoli Jr., J. Med. Chem., 1990, 33, 2221.
7. W. L. Mendelson, C. B. Spainhour Jr., S. S. Jones, B. L. Lam and K. L. Wert, Tetrahedron Lett., 1980, 21, 1393.
8. W. E. Bondinell, F. W. Chapin, G. R. Girard, C. Kaiser, A. J. Krog, A. M. Pavloff, M. S. Schwartz, J. S. Silvestri, P. D. Vaidya, B. L. Lam, G. R. Wellman and R. G. Pendleton, J. Med. Chem., 1980, 23, 506.
9. J. Gal, R. J. Wienkam and N. Castagnoli Jr., J. Org. Chem., 1974, 39, 418.
10. G. Fodor, J. Gal and B. A. Phillips, Angew. Chem., Int. Ed. Engl., 1972, 11, 919.
11. W. M. Whaley and T. R. Govindachari, Org. React., 1951, 6, 74.
12. E. D. Cox and J. M. Cook, Chem. Rev., 1995, 95, 1797.
13. W. M. Whaley and T. R. Govindachari, Org. React., 1951, 6, 151.
14. J. M. Bobbitt, in Advances in Heterocyclic Chemistry, ed. A. R. Katritzky and A. J. Boulton, Academic Press, New York, 1973, p. 99.
15. W. J. Gensler, Org. React., 1951, 6, 191.
16. T. J. N. Watson, J. Org. Chem., 1998, 63, 406.
17. G. E. Stokker, Tetrahedron Lett., 1996, 37, 5453.
18. N. Sotomayor, E. Domínguez and E. Lete, Tetrahedron, 1995, 51, 12159.
19. A. Kubo, N. Saito, N. Kawakami, Y. Matsuyama and T. Miwa, Synthesis, 1987, 9, 824.
20. L. W. Deady, N. Pirzada and R. D. Topsom, J. Chem. Soc., Chem. Commun., 1971, 799.
21. A. R. Katritzky, X. Lan, J. Z. Yang and O. V. Denisko, Chem. Rev., 1998, 98, 409.
22. A. R. Katritzky, X. Lan and W.-Q. Fan, Synthesis, 1994, 5, 445.
23. A. R. Katritzky, S. Rachwal and G. J. Hitchings, Tetrahedron, 1991, 47, 2683.
24. J. H. Burckhalter, V. C. Stephens and L. A. R. Hall, J. Am. Chem. Soc., 1952, 74, 3868.
25. A. R. Katritzky, S. Rachwal and B. Rachwal, J. Chem. Soc., Perkin Trans. 1, 1987, 799.
26. A. R. Katritzky, X. Lan and Z. Zhang, J. Heterocycl. Chem., 1993, 30, 381.
27. A. R. Katritzky and X. Lan, Chem. Soc. Rev., 1994, 23, 363.
28. A. R. Katritzky, H. Lang and X. Lan, Tetrahedron, 1993, 49, 2829.
29. A. R. Katritzky, K. Yannakopoulou, P. Lue, D. Rasala and L. Urogdi, J. Chem. Soc., Perkin Trans. 1, 1989, 225.
30. A. R. Katritzky, W.-Q. Fan and Q.-H. Long, Synthesis, 1993, 2, 229.
31. A. R. Katritzky, S. Rachwal and R. Ollmann, J. Heterocycl. Chem., 1994, 31, 775.
32. M. Okamoto and M. Yamada, Chem. Pharm. Bull., 1963, 11, 554.
33. Dictionary of Alkaloids, ed. I. W. Southon and J. Buckingham, Chapman and Hall, London, 1989.
34. M. Schlosser, G. Simig and H. Geneste, Tetrahedron, 1998, 54, 9023.
35. R. M. Williams, P. P. Ehrlich, W. Zhai and J. Hendrix, J. Org. Chem., 1987, 52, 2615.
36. Dictionary of Organic Compounds, ed. J. Buckingham, Chapman and Hall, New York, 1982.
37. Ochiai and Nakagome, Yakugaku Zasshi, 1958, 78, 1438 (Chem. Abstr., 1959, 8138).