The HgCl2-promoted guanylation reaction: The scope and limitations

Tetrahedron

Volumn 53, Issue 14, 1997, Pages 5291-5304

  Levallet, Catherine ^a   Lerpiniere, Joanne ^a   Ko, Soo Y ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GUANIDINE DERIVATIVE; MERCURY CHLORIDE; THIOUREA DERIVATIVE;

ARTICLE; CATALYSIS; DRUG SYNTHESIS; PRIORITY JOURNAL;

EID: 0030936351     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(97)00193-2     Document Type: Article

References (23)

1. Greenhill, J. L.; Lue, P. Amidines and Guanidines in Medicinal Chemistry in "Progress in Medicinal Chemistry" Vol. 30, Chapt. 5, Ellis, G. P.; Luscombe, D. K. eds. Elsevier Science, 1993.
2. Yamamoto, Y.; Kojima, S. in "The Chemistry of Amidines and Imidates" Vol. 2, Chapt. 10, Patai, S.; Rappoport, Z. eds. John Wiley & Sons: New York, 1991.
3. Kim, K. S.; Qian, L. Tetrahedron Lett. 1993, 34, 7677.
4. (a) Ramadas, K.; Srinivasan, N. Tetrahedron Lett. 1995, 36, 2841.
5. (b) For a related reaction, see: Ramadas, K. Tetrahedron Lett. 1996, 37, 5161.
6. (a) Poss, M. A.; Iwanowicz, E.; Reid, J. A.; Lin, J.; Gu, Z. Tetrahedron Lett. 1992, 33, 5933.
7. (b) Atwal, K. S.; Ahmed, S. Z.; O'Reilly, B. C. Tetrahedron Lett. 1989, 30, 7313.
8. Ko, S. Y.; Lerpiniere, J.; Christofi, A. M. Synlett 1995, 815.
9. (a) In a 1-guanylpyrazole-based guanylation, the bis-Boc protected reagent was found to be more reactive than the unprotected parent compound, which in turn was more reactive than the mono-Boc protected reagent. See: Bernatowicz, M. S.; Wu, Y.; Matsueda, G. R. Tetrahedron Lett. 1993, 34, 3389.
10. (b) Tian, Z.; Edwards, P.; Roeske, R. W. Int. J. Peptide Protein Res. 1992, 40, 119.
11. (c) Bergeron, R. J.; McManis, J. S. J. Org. Chem. 1987, 52, 1700.
12. (d) Yuan, C.; Williams, R. M. Tetrahedron Lett. 1996, 37, 1945.
13. 2-promoted N-Boc-guanylation was recently reported while the present work was in progress. See: Jeong, J.-H.; Murray, B. W.; Takayama, S.; Wong, C.-H. J. Am. Chem. Soc. 1996, 118, 4227.
14. Barton, D. H. R.; Fontana, G.; Yang, Y. Tetrahedron 1996, 52, 2705.
15. A recent report described a use of an N-sulfonylguanidine as an acid-labile linker to a solid support. See: Bonnat, M.; Bradley, M.; Kilburn, J. D. Tetrahedron Lett. 1996, 37, 5409.
16. A similar in-situ preparation of N-cyanoguanidines was reported in the literature. See: Tiley, J. W.; Ranuz, H.; Levitan, P.; Blount, J. F. Helv. Chim. Acta 1980, 63, 841.
17. (a) Ganellin, R. J. Med. Chem. 1981, 24, 913.
18. (b) Durant, G. J.; Emmett, J. C.; Ganellin, C. R.; Miles, P. D.; Parsons, M. E.; Prain, H. D.; White, G. R. J. Med. Chem. 1977, 20, 901.
19. (a) We were able to isolate the less-polar intermediates when the guanylation reactions were performed, with selected thiourea substrate, either in the absence of, or in the presence of less than 1 equivalent of the incoming amine (tetrahydroisoquinoline). The intermediates were characterized to be the corresponding carbodiimides.
20. 2-promoted guanylation process, i.e., faster reactions with electron-withdrawing substituents and slower reactions with electron-donating groups.
21. For a review on the chemistry of carbodiimides, see: Mikolajczyk. M.; Kielbasinski, P. Tetrahedron 1981, 37, 233.
22. (a) Elemental analyses indicate that the guanidine products were obtained, depending on the nature of the substituents, as either free base, the mono-, or di-hydrochloride salt forms. Thus, the guanidines substituted with electron-withdrawing groups (e.g., the products of Tables 1 and 2, p-nitrophenyl-and p-methoxycarbonylphenyl-substituted guanidines [entries 1 and 3, Table 3]) were obtained as free-base; p-trifluoromethylphenyl-and p-chlorophenyl-substituted guanidines (entries 2 and 4, Table 3) were obtained as the mono-hydrochloride forms; electron-donating group-substituted phenyl-guanidines (entries 5-7, Table 3) were obtained as the di-hydrochloride salts.
23. (b) The stoichiometry of the salt forms simply reflects the basicity of the substituted guanidine products. See reference 2 for the effects of the substituents on the basicity of substituted guanidines.