Chloroformamidinium Salts; latest and efficient reagent for preparation of 2-aminobenzothiazole derivatives.
In bioorganic and medicinal chemistry 2-aminobenzothiazoles derivatives are broadly found with applications in drug discovery and development of the treatments of diabetes1, epilepsy2,3, inflammation4, amyotrophic lateral sclerosis5, analgesia6, tuberculosis7, and viral infection8. Riluzole9 (1) was chemically a 2-aminobenzothiazole derivative that is 6-(trifluoromethoxy)-2-benzothiazolamine and was found to interfere with glutamate neurotransmission in biochemical, electrophysiological and behavioral experiments. In 1887,Hoffmann10 first reported the cyclizations of 2- aminothiophenol to 2-aminobenzothiazoles. Hofmann noted only formation of 2- anilinobenzothiazole from the reaction of 2-aminothiophenol and phenyl isothiocyanate.
Investigations into the preparation of 2-aminobenzothiazoles can also be traced to the early 1900s with work of Hugerschoff, who found that an arylthiourea can be cyclized with liquid bromine in Chloroform to form a 2-aminobenzothiaozles11, 12. The reaction of molecular bromine (Br2) with arylthioureas is known as Hugerschoff Reaction (2).
Johanson and Hamillton13 prepared 2-amino-6-methylmercaptobenzothiazole by oxidation of 4-Methylmecaptophenylthiourea with Bromine as a catalyst (3). Stuckwisch 14, using potassium thiocyanate cyclizing p-substituted aniline into 2-amino-6-substituted benzothiazole and bromine as a catalyst (4). Allen and VanAllan 15 , using sodium thiocyanate cyclizing p-substituted aniline into 2-amino-6-substituted benzothiazole and sulfuric acid as a catalyst (5). Caldwell et. al.16 synthesized 2-anilinobenzothiazole with help of S-o-aminophenyl hydrogen thiosulphate and phenyl isothiocyanate in pyridine and aqueous sodium carbonate (6).
Tweit17 was done cyclizations of isothiocyanates to 2-aminobenzothiazole in presence of benzene (7). Alaimo18 was prepared 2-amino-5, 6-dichloro and 2-amino-6, 7-dichlorobenzothiazole by cyclized the suitable substituted aniline with help of thiocyanogen (8). Jeng Li and Kasina19 were prepared 6-substituted-2-aminobenzothiazole by cyclizations of p-substituted anilines with the help of ammonium thiocyanate and bromine (9). Naim et. al.20 were synthesized 2-aminobenzoyhiazole-6-carboxalic acid and 2-amino-6-substituted-carbonyl benzothiazoles by reaction of the corresponding 4-substituted anilines with potassium thiocyanate followed by oxidative cyclizations of the resultant thioureas with bromine (10).
Castro and Martinez21 were synthesized 2-aminoethylbenzothiazole by intramolecular oxidations in N-ethyl-N'-phenylthiourea in presence of sulphuryl chloride and toluene (11). Hendery22, Nargund et. al. 23, 24, Pattan et. al.25 (12) was prepared the 2-amino-6-fluoro-7-chlorobenzothiazole by cyclized 3-chloro-4-fluoroaniline by potassium thiocyanate in presence of catalytic bromine. Morlacchi et. al.26 were also synthesized 6-fluoro-4(5 or 7)-chloro-2-aminobenzothiazoles by using similar method and materials which was used by Pattan et al (12).
Patel and Agravat27 were synthesized various 4(5 or 6)-substituted-2-aminobenzothiazoles with help of 4(5 or 6)-substituted anilines which was reacted with ammonium thiocyanate and bromine (13). Jimonet et. al.28 were synthesized various substituted-2-benzothiazolamines derivatives by different method. Method A: One-pot reaction of appropriate anilines with thiocyanogen generated from bromine and alkaline thiocyanate in acetic acid medium led to formation of the desired product in good to moderate yields (14). Method B: In this method cyclization of phenylthiourea with bromine in chloroform (15).
Matsui et. al.29was prepared6-substituted-2-aminobenzothiazoles by the reaction of 4-substituted anilines with potassium thiocyanate in presence of bromine (16). Jordan et. al.30 using Benzyltrimethylammonium tribromide (PhCH2NMe3Br3), is a stable, electrophilic bromine source for the conversion of substituted arylthioureas to 2-aminobenzothiazoles under mild conditions in a variety of solvents with good yields. One of the key benefits for this reagent when compared with molecular bromine in ease of addition and handling, which minimizes the risk of forming brominated side products. They have extended the use of this reagent to a direct, one-pot synthesis of 2-aminobenzothiazoles from either aryl isothiocyanate and anilines or tetrabutylammonium thiocyanate and anilines in the presence of a stoichiometric amount of Ph CH2NMe3Br3 (17).
Yong-Qian Wu et. al.31 using Di(imidazole-1-yl)methanimine for formation of nitrogen containing heterocyclic nucleus. Di(imidazole-1-yl)methanimine was synthesized by treating cyanogens bromide with imdazole based on a previously reported procedure32, 33. As shown in (18), the reaction of went smoothly with 2-substituted anilines, regardless of their nucleophilicity and this may suggest that second imidazole displacement is not the rate-limiting step due to the strong tendency towards cyclizations.
Batey et. al.34 35 reported the synthesis of 2-aminobenzoyhiazoles through analogous C-S bond forming methodologies. They formed the intramolecular C-S bond with the help of Copper- and palladium-catalyzed. Copper- and palladium-catalyzed intramolecular C-S bond formation by cross-coupling between an aryl halide and thioureas functionality is demonstrated for the synthesis of 2-aminobenzothiazoles, wherein Cu-catalyzed protocol is generally superior and more effective than the Pd-catalyzed protocol and intramolecular 2-aminobenzothiazole synthesis from ortho-bromo and –iodo-arylthioureas (19).
El-Faham et. al.36 synthesized 2-aminobenzothiazoles derivatives by using efficient reagents that is Chloroformamidinium salts. Chloroformamidinium salts were prepared as method described previously37, 38 and allowed to react with o-substituted aniline to afford 2-aminobenzothiazole (21). Compounds could be formed by two alternative routes (A or B), depending on the nucleophicity of the X substituent of o-substituted anilines. Route A, if X is more nucleophilic than the anilino nitrogen atom, the lone pair of X would first attack the central atom of the Chloroformamidinium salts, displacing the chloride ion to form intermediate which then undergoes the in situ heterocyclization with the loss of dimethylamine as a better leaving group to afford the expected product, as in case of the reaction of o-aminothiophenol with the Chloroformamidinium salts and Route B mainly for synthesis 2-aminobenzoimidazole or 2-aminobenzoxazole.
Although 2-aminobenzothiazole derivatives like 6-trifluoromethoxy-2-aminobenzothiazole [Riluzole (1)] are reported to have pharmacological activity. This review also showed that 2-aminobenzothiazole derivatives are easy to prepared by using different catalysts or agents. There is still scope for more research work to be done in this field to find a novel agent. This study would be useful for the research working in this field.
1.Suter, H. and Zutter, H., Helv. Chim. Acta, 1967, 50, 1084.
2. Hays, S. J., Rice, M. J., Ortwine, D. F., Johnson G., Schwartz, R. D., Boyd, D. K., Copeland, L. F., Vartanian, M. G. and Boxer, P. A., J. Pharm. Sci., 1994, 83, 1425.
3.He, Y., Benz, A., Fu, T., Wang, M., Covey, D. F., Zorumski, C. F. and Mennick, S., Neuropharmacology, 2002, 42, 199.
4.Sawhney, S. N., Arora, S. K., Singh, J. V., Bansal, O. P. and Singh, S. P., Ind. J. Chem., 1978, 16B, 605.
5.Bensimon, G., Lacomblez, L., Meininger, V. and New Eng. J. Med., 1994, 330, 585.
6.Foscolos, G., Tsatsas, G., Champagnac, A. and Pommier, M., Ann. Pharm. Fr., 1977, 35, 295.
7.Shirke, V. G., Bobade, Bhamaria, R. P., Khadse, B. G. and Sengupta, S. R., Indian Drugs, 1990, 27(6), 350.
8.Paget, C. J., Kisner, K., Stone, R. L. and Delong, D. C., J. Med. Chem., 1969, 12, 1016.
9.Bryson, M., Fulton, B. and Benfield, P., Drugs, 1996, 52, 549.
10. Hofmann, A. W., Ber., 1887, 20, 1788.
11. Hugerschoff, H., Chem. Ber., 1901, 34, 3130. (b) Hugerschoff, H., Chem. Ber., 1903, 36, 3121.
12. Sprague, J. M., Land, A. H., In Heterocyclic Compounds; Elderfield, R. C.; J. Wiley: New York, 1957, Vol. 5, Chapter 8, p. 484-721.
13. Johanson, F. E. and Hamillton, C. S., J. Amer. Chem. Soc., 1949, 71, 74.
14. Stuckwisch, C. G., J. Amer. Chem. Soc., 1949, 71, 3417.
15. Allen, C. F. H. and Van-Allan J., Organic Synthesis, 1942, 22, 16. (b) 1955, 3, 76.
16. Caldwell, J. B., Milligan, B. and Swan, J. M., J. Chem. Soc., 1963, 2097.
17. Tweit, R. C., J. Chem. Soc., 1970, 687.
18. Alaimo, R. J., J. Chem. Soc., 1971, 309.
19. Lin, A. J. and Kasina, S., J. Heterocycl. Chem., 1981, 18, 759.
20. Naim, S. S., Singh, S. K. and Sharma S., Indian J. Chem., 1991, 30B, 494.
21. Martinez, A. and Castro, A., J. Heterocycl. Chem., 1999, 36, 991.
22. Hendry, C. M., J. Amer. Chem. Soc., 1958, 80, 973.
23. Gurupadaiah, B. M., Jayachandran, E., Shivakumar, B., Nagappa, A. N. and Nargund, L. V. G., Indian J. Heterocycl. Chem., 1998, 7, 213.
24. Jayachandran, E., Shivakumar, B., Nargund, L. V. G. and Bhatia, K., Orient. J. Chem., 2003, 19(1), 139.
25. Pattan, S. R., Ch Suresh, Pujar, V. D., Reddy, V. V. K., Rasal, V. P. and Koti, B. C., Indian J. Chem., 2005, 44B, 2404.
26. Morlacchi, F., Armenise, D., De Laurentis, N., Reho, A. and Rosato, A., J. Heterocycl. Chem., 2004, 41, 771.
27. Patel, N. B. and Agravat, S. N., Orient. J. Chem., 2006, 22(2), 333.
28. Jimonet, P., Audiau, F., Barreau, M., Blanchard, J. C., Boireau, A., Bour, Y., Coleno, M. A., Doble, A., Doerflinger, G., Huu, C. D., Donat, M. H., Duchesne, J. M., Ganil, P., Gueremy, C., Honore, E., Just, B., Kerphirique, R., Gointer, S., Hubert, P., Laduron, P. M., Le Blevac, J., Meunier, M., Miquet, J. M., Nemecek, C., Pasquet, M., Piot, O., Pratt, J., Rataud, J., Reibaud, M., Stutzmann, J. M. and Mignani, S., J. Med. Chem., 1999, 42, 2828.
29. Matsui, M., Marui, Y., Kushida, M., Funabiki, K., Muramastu, H., Shibata, K., Hirota, K., Hosoda, M. and Tai, K., Dyes and Pigments, 1998, 38, 57.
30. Jordan, A. D., Chi Luo and Retiz, A. B., J. Org. Chem., 2003, 68, 8693.
31. Wu, Y. Q., Limburg, D. C., Wilkinson, D. E. and Hamilton, G. S., J. Heterocycl. Chem., 2003, 40, 191.
32. Ferris, J. P., Huang, C. H. and Hagan, W. J., Nucleosides and Nucleotides, 1989, 8(3), 407.
33. Wu, Y. Q., Hamilton, S., Wilkinson, D. E. and Hamilton, G. S., J. Org. Chem., 2002, 67(21), 7553.
34. Batey, R. A., Joyee, L. L. and Evindar, G., Chem. Commun., 2004, 446.
35. Batey, R. A. and Evindar, G., Org. Lett., 2003, 5, 133.
36. El-Faham, A., Chebbo, M., Abdul-Ghani, M. and Younes, G., J. Heterocycl. Chem., 2006, 43, 599.
37. El-Faham, A., Chem. Lett., 1998, 671
38. Carpino, L. A. and El-Faham, A., J. Amer. Chem. Soc., 1995, 117, 5401.
SBMN Institute of Pharmaceutical Sciences & Research, Asthal Bohar, Rohtak