Abstract
3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2-aminothiazole derivative 3 via bromination of 1 followed by treatment of the formed acetylbromide 2 with thiourea or via Bignailli reaction of 1. Treatment of 3 with 2 afforded the bis-coumarin 4, whereas, cyanoacetylation of 3 followed by treatment of the formed cyanoacetamide 6 with salicyaldehyde give the bis-coumarin 7. Reaction of 6 with phenyl isothiocyanate in DMF/KOH produced the potassium salt 8, which cyclized with chloroacetyl chloride to give the thiazolidinone 9. Acidification of 8 with HCl afforded the thiocarbamoyl 10, which condensed with 2 in DMF to give the mercapto derivative 12, whereas in DMF/TEA gave the thiophene derivative 13. The thiophenes 15a–c were achieved via treatment of the thiocarbamoyls 14a–c with 2 in DMF/TEA, whereas, in DMF gave the corresponding thiazoles 16a–c. Treatment of the components 17a, b with carbon disulfide in DMF/KOH followed by addition of 2 afforded the dithioacetals 19a, b. Cyclization of 19b under alkaline condition gave the desired thiophene 20. Representative compounds of the synthesized products were evaluated as antitumor and antioxidant agents.
Graphical Abstract
3-Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of different coumarin derivatives. Newly synthesized compounds were elucidated by analytical and spectral data. Representative compounds of the synthesized products were evaluated as antitumor and antioxidant agents.
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Acknowledgments
The authors thank Dr. Serry A.A. El Bialy for carrying out the microbiology screening, Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
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Gouda, M.A., Berghot, M.A., Baz, E.A. et al. Synthesis, antitumor and antioxidant evaluation of some new thiazole and thiophene derivatives incorporated coumarin moiety. Med Chem Res 21, 1062–1070 (2012). https://doi.org/10.1007/s00044-011-9610-8
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DOI: https://doi.org/10.1007/s00044-011-9610-8