Synthesis of some trifluoromethylated indolones

Hadijatu Mumini Kamara, Tennessee State University


The indole core is a ubiquitous substructure in many natural products and biologically active compounds. Due to their biological activity, indole-based compounds attract special attention as building block for the development of therapeutic agents. 5-Trifluoromethyl-1,3-cyclohexandione previously developed in our lab as a multi-faceted trifluoromethyl building block, was reacted with a range of acid chlorides to give different tricarbonyl compounds in a one-pot multi-component reaction. In this report, we describe the synthesis of novel fluorinated 6, 7-dihydro-1H-indol-4 (5H)-ones as potential antitumor agents. Starting with the above tricarbonyl compound, we have been able to synthesize several of these derivatives. In addition, the tricarbonyl compounds are further cyclized with amines and aniline in the presence of acetic acid to produce trifluoromethylated Indolones in moderate to good yields. The hypotheses are the trifluoromethylated Indolones will display anticancer activity in several human cell lines. Their antitumor activity will be investigated using established procedures. 2-(2-(4-chlorophenyl)-2-oxoethyl)-5-(trifluoromethyl) cyclohexane-1, 3-dione was prepared from 5-trifluoromethyl-1, 3-cylohexanedione and 2-bromo-4-chloroacetophenone in the presence of dry chloroform. 11 novel fluorinated 6, 7-dihydro-1H-indol-4(5H) were prepared by treatment with fluorinated tricarbonyl compounds and substituted anilines/amines in acetic acid. 8 bis-spiro piperidines were prepared via a three-component condensation of anilines and one equivalent of 5-trifluoromethyl-1, 3-cyclohexanedione in the presence of excess formaldehyde. In addition, 6 6,6-dimethyl-1-phenyl-2-(trifluoromethyl)-6,7-dihydro-1H-inden-4(5H) one was prepared by reacting diketones with anilines in the presence of acetic acid and was refluxed for 24h at 60°C. All of the above compounds were purified by either column chromatography or by recrystallizion, and was further characterized by infrared spectroscopy (IR), Nuclear Magnetic Resonance spectroscopy (NMR), gas chromatography mass spectroscopy (GC-MS) and Liquid chromatography mass spectroscopy LC-MS. In the future this research will focus on determining the mechanism by which these novel fluorinated compounds inhibit tumor growth.

Subject Area

Analytical chemistry|Organic chemistry|Medicine

Recommended Citation

Hadijatu Mumini Kamara, "Synthesis of some trifluoromethylated indolones" (2012). ETD Collection for Tennessee State University. Paper AAI1510433.