An improved large-scale preparation of benzimidazole-2-sulfonic acids and 2-chlorobenzimidazoles

Synthetic Communications

Volumn 28, Issue 9, 1998, Pages 1703-1712

  Hinkley, Jack M ^c   Porcari, Anthony R ^c   Walker II, John A ^a   Swayze, Eric E ^b   Townsend, Leroy B ^c  

^a ALZA CORPORATION   (United States)

^b ISIS PHARMACEUTICALS   (United States)

^c NONE

Author keywords

[No Author keywords available]

Indexed keywords

2 CHLOROBENZIMIDAZOLE; 2 CHLOROBENZIMIDAZOLE NUCLEOSIDE; BENZIMIDAZOLE 2 SULFONIC ACID; BENZIMIDAZOLE DERIVATIVE; SULFONIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIVIRAL ACTIVITY; ARTICLE; DRUG CONFORMATION; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

EID: 0031967043     PISSN: 00397911     EISSN: None     Source Type: Journal    
DOI: 10.1080/00397919808006874     Document Type: Article

References (27)

1. a) Townsend, L. B.; Revankar, G. R. Chem. Rev. 1970, 70, 389-438.
2. b) Revankar, G. R.; Townsend, L. B. J. Heterocycl. Chem. 1968, 5, 477-483.
3. c) Revankar, G. R.; Townsend, L. B. J. Heterocycl. Chem. 1968, 5, 615-620.
4. Townsend, L. B.; Devivar, R. V.; Turk, S.R.; Nassiri, R. M.; Drach, J. C. J. Med. Chem. 1995, 38, 4098-4106.
5. Swayze, E. E.; Peiris, S. M.; Kucera, L. S.; White, E. L.; Wise, D. S.; Drach, J. C.; Townsend, L. B. Bioorg. & Med. Chem. Lett., 1993, 3, 543-546.
6. Preston, P. N. Chem. Rev. 1974, 74, 279-314; Preston, P. N. In: Benzimidazoles and Congeneric Tricyclic Compounds, Part I; Preston, P. N. Ed.; John Wiley and Sons: New York, 1981; pp 193-196.
7. Preston, P. N. Chem. Rev. 1974, 74, 279-314; Preston, P. N. In: Benzimidazoles and Congeneric Tricyclic Compounds, Part I; Preston, P. N. Ed.; John Wiley and Sons: New York, 1981; pp 193-196.
8. Harrison, D.; Ralph, J. T.; Smith, A. C. B. J. Chem. Soc. 1963, 2930-2937.
9. Kawashima, E.; Gupta, P. K.; Devivar, R. V.; Townsend, L. B. In: Nucleic Acid Chemistry. Improved and New Synthetic Procedures, Method and Techniques, Part. 4; Townsend, L. B.; Tipson, R. S., Eds. John Wiley and Sons: New York, 1991; pp 24-26.
10. Mandel, L. R.; Porter, C. L.; Kuehl, F. A. Jr.; Jensen, N. P., Schmidt, S. M., Windholz, T. B., Beattie, T. R., Carty, J. A., Christensen, B. G., Shen, T. Y. J. Med. Chem. 1970, 13, 1043-1047.
11. Balli, H. and Kersting, F. J. Leibigs Ann. Chem. 1961, 647, 1-8.
12. Frick, W. E. and Wenger, T. US 3555040, CA 74:141791y.
13. Van Allen, J. A. and Deacon, B. D. Org. Syn. Coll. Vol. IV, 569.
14. Everett, J. G. J. Chem. Soc. 1930, 2402-2408.
15. Sorba, G.; Garrone A.; Serafino, A.; Gasco, A.; Orsetti, M. Eur. J. Med. Chem. 1986, 21, 391-396.
16. Ando, T.; Cork, D. G.; Kimura, T. Chem. Letters 1986, 665-666.
17. For a review of the chemistry of sodium percarbonate and sodium perborate see McKillop, A. and Sanderson, W. R. Tetrahedron 1995, 51, 6145-6166.
18. The acid gas effluent can be scrubbed by continuous water flow as described in ref. 16.
19. Allen, C. F. H. Org. Syn. Coll. Vol. II, 3-5.
20. Acheson, R. M.; Taylor, G. A.; Tomlison, M. L. J. Chem. Soc. 1958, 3750.
21. It was found that the best conditions for reduction were to use a minimum of 10 mL ethanol and 0.1 g of Raney nickel per gram of 4,5-dichloro-2-nitroaniline. By decreasing the volume of solvent the product precipitates on the catalyst.
22. Joseph, L. and Albert, A. H. J. Heterocycl. Chem. 1966, 3, 107-108.
23. Buechel, K. H. (Shell Oil Co.) US 3,369,028. Chem. Abstr. 1968, 69, 36136N.
24. The reaction times for each compound respectively were 12 hr and 24 hr. It is recommended that potassium ethyl xanthate be prepared in situ and the benzimidazole-2-thiones be reprecipitated before use.
25. f values for the benzimidazole-2-sulfonic acids are very low (<0.2).
26. This is needed to control the initial extremely exothermic reaction that occurs on heating.
27. This is conveniently carried out by dividing the reaction mixture into two or three portions contained in 20 L plastic buckets. The time required for neutralization is reduced to approximately 2 hr.