DOI: https://doi.org/10.24959/ophcj.13.751

Carbon-carbon and carbon-heteroatom conjugate addition of n-substituted maleimides to 4h-1,2,4- triazol-3-thioles, 2-amino-1,3-thiazoles, 1h-imidazole and 2-phenylindolizine catalyzed by lewis acids

T. V. Matviiuk, M. V. Gorichko, C. Lherbet, M. Baltas, Z. V. Voitenko

Abstract


In the paper the cheap and effective method of the synthesis of 3-heteryl substituted succinimides via catalytic Michael addition are presented. Lewis acids have been found to be effective catalysts for conjugate addition of N-aryl substituted maleimides to the heterocycles with donor-heteroatoms or CH-active function. Catalytic reactions proceed in mild conditions without formation of by-products that are often present in the classical Michael reaction. The compounds synthesized are promising and interesting substrates for biological evaluation since numerous natural products, drugs and drug candidates bear the succinimide core. Moreover, regioselectivity of addition of ambident heterocyclic nucleophiles such as 4H-1,2,4-triazole-3-thiole, 1H-imidazole and 2-amino- 1,3-thiazole to maleimides have been investigated. Lewis acids such as aluminium chloride, zinc chloride and lithium perchlorate have been tested on different heterocyclic substrates as catalysts. Interestingly, depending on nucleophilicity of the substrate different Lewis acids have shown significantly varying efficacy. In this respect aluminium chloride was identified as the most effective catalyst for C–C addition among the Lewis acids tested. Lithium perchlorate appears to be the most efficient in the case of C–N addition with the endocyclic nitrogen atom of the hererocycle. Zinc chloride shows a good catalytic efficacy in addition of maleimides to the exocyclic amino group of 2-aminothiazole. Finally, the advantages of the catalytic approach developed such as mild reaction conditions, easy handling, low toxicity of the catalysts and their low cost make this method useful for the synthesis of new 3-heteryl substituted succinimides, which, in turn, are interesting substrates in medicinal chemistry.


Keywords


Michael addition; catalyst; maleimide; Lewis acids; succinimide, regioselectivity

Full Text:

PDF

References


Comelles J., Moreno-Manas M., Vallribera A. // Arkivoc. – 2005. – Vol. 9, – P. 207-238.

Shintani R., Duan W.-L., Nagano T. et al. // Angew. Chem. Int. Ed. – 2005. – Vol. 44, №29. – P. 4611-4614.

Shrestha R.Y., Shen K.A., Pollack J-S. A. et al. // BioconJugate Chem. – 2012. – Vol. 23, №3. – P. 574-585.

Harada S., Kumagai N., Kinoshita T. et al. // J. Am. Chem. Soc. – 2003. – Vol. 125, №9. – P. 2582-2590.

Bartoli G., Bosco M., Carlone A. et al. // Angew. Chem. Int. Ed. – 2006. – Vol. 45, №30. – P. 4966-4970.

Ballini R., Palmieri A. // Adv. Synth. Catal. – 2006. – Vol. 348, №10-11. – P. 1154-1156.

Almasi D., Alonso D.A., NaJera C. // Tetrahedron: Asymmetry. – 2007. – Vol. 18, №3. – P. 299-365.

Voitenko Z.V., Pokholenko O.A., Shkarov O.O. et al. // Eur. J. Org. Chem. – 2001. – №7. – P. 1401-1405.

Pokholenko O.A., Voitenko Z.V., Kovtunenko V.O. // Russ. Chem. Reviews. – 2004. – Vol. 73, №8. – P. 771-784.

Voitenko Z.V., Pokholenko O.A., Shkarov O.O. et al. // Chemistry of Heterocyclic Compounds. – 2002. – Vol. 38, №2. – P. 190-196.

Matviiuk T., Gorichko M., Kysil A. et al. // Synth. Comm. – 2012. – Vol. 42. – P. 3304-3310.

Bartoli G., Bosco M., Marcantoni E. et al. // Tetrahedron Lett. – 2002. – Vol. 43. – P. 6331-6333.

Snyder H.S. Drugs and the Brain. – New York: Scientific American Library, 1986.

Crider A.M., Kolczynski T.M., Yates K.M. // J. Med. Chem. – 1980. – Vol. 23, №3. – P. 324-326.

Ando Y., Fuse E., Figg W.D. // Clin. Cancer Res. – 2002. – Vol. 8, №6. – P. 1964-1973.

Freiberg C., Fischer H.P., Brunner N.A. // Antimicrob. Agents Chemother. – 2005. – Vol. 49, №2. – P. 749-759.

Fredenhagen A., Tamura S.Y., Kenny P.T.M. et al. // J. Am. Chem. Soc. – 1987. – Vol. 109. – P. 4409-4411.

Freiberg C., Brunner N.A., Schiffer G. et al. // J. Biol. Chem. – 2004. – Vol. 279, №25. – P. 26066-26073.

Isaka M., Rugseree N., Maithip P. et al. // Tetrahedron. – 2005. – Vol. 61, №23. – P. 5577-5583.

Menendez C., Gau S., Lherbet C. et al. // Eur. J. Med. Chem. – 2011. – Vol. 46, №11. – P. 5524-5531.

Menendez C., Chollet A., Rodriguez F. et al. // Eur. J. Med. Chem. – 2012. – Vol. 52. – P. 275-283.

Hiroshi M., Hiroyuki I. // Jpn. Tokkyo Koho. – 1972. – JP 47004963 B4 19720212.

Ramachandraiah G., Reddy K. Kondal // Ind. J. of Chem., Section B: Organic Chemistry Including Med. Chem. – 1985. – Vol. 24B, №8. – P. 808-810.

PohJala E. // Tetrahedron Lett. – 1972. – Vol. 13, №25. – P. 2585-2588.


GOST Style Citations






Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)