Condensation reactions of indole with acetophenones affording mixtures of 3,3-(1-phenylethane-1,1-diyl)bis(1H-indoles) and 1,2,3,4-tetrahydro-3-(1H-indol-3-yl)-1-methyl-1,3-diphenylcyclopent[b]indoles

Abstract

Melting points were measured with a Mel-Temp apparatus, and were not corrected or calibrated. Rf values obtained using SiO2 in 1:2 EtOAc:hexane. Infrared spectra were collected on a Thermo Fisher Scientific Nicolet iS5 spectrophotometer. 1 H NMR and 13 C NMR spectra were recorded on AV-500 Bruker Avance III HD, HD-500 Bruker Avance III HD, or AM-400 Bruker Avance III HD spectrometers at ambient temperature and are referenced to the solvent.Mass spectra were recorded on a Bruker Biotof II instrument using poly(ethylene glycol) as an internal calibrant, or on an Agilent 7890B gas chromatograph using an Agilent DB-5MS 250 µm capillary column with an Agilent 7200 GC/QTOF-MS detector calibrated with external perfluorotributylamine. Reagents and solvents were used as purchased. General procedures Method A: Reactions of indole with acetophenones in ethanolic HCl at RTIndole 1a (0.234 g, 2.00 mmol, 1 eq), naphthalene 10 (0.064 g, 0.50 mmol, 0.25 eq), and acetophenone 8a-h (3.00 mmol, 1.5 eq) were dissolved in ethanol (10 mL). Concentrated hydrochloric acid (1 mL) was added dropwise at room temperature. The resulting solution was allowed to stirred at RT for 5 d. The reaction mixture was neutralized using sat. sodium bicarbonate (25 mL) and the organic layer was extracted with dichloromethane (4 × 25 mL). The combined organic extracts were dried with magnesium sulfate, filtered, and excess solvent was removed with a rotary evaporator. The resulting mixtures were analyzed using 1 H NMR spectroscopy, with naphthalene as the internal integration standard. The crude mixture was dry-S2 loaded onto silica gel and the products were purified by column chromatography or MPLC using EtOAc:hexane as the eluent. Method B: Reactions of indole with acetophenones in ethanolic HCl at 40 o CThis procedure is identical with Method A, except reactions were stirred at 40 o C for 3 d before neutralization. Method C: Reactions of indole with acetophenones in refluxing acetic acidIndole 1a (1.171g, 10.00 mmol, 1eq) and acetophenone 8a-h (12.00 mmol, 1.2 eq) were dissolved in acetic acid (1 mL) and then refluxed overnight. The reaction mixture was neutralized using sat. sodium bicarbonate (10 mL) and the organic layer was extracted with dichloromethane (4 × 25 mL). The combined organic extracts were dried with magnesium sulfate, filtered, and excess solvent was removed with a rotary evaporator. The crude mixture was dry-loaded onto silica gel and purified by column chromatography using EtOAc:hexane as the eluent, giving products 11a-h. S32:1 condensation products: Bisindoles (11a-h) 3,3'-(1-phenylethane-1,1-diyl)bis(1H-indole) (11a) [46] was prepared by Method A from 8a (361 mg) as a white crystalline powder; 130 mg, 37% (calcd by 1 H NMR); mp 118-120 o C (lit.

CF3SO2Na-Mediated, UV-Light-Induced Friedel–Crafts Alkylation of Indoles with Ketones/Aldehydes and Bioactivities of Products

“…Because of their biological potential, DIMs have received much attention in organic synthesis, and several highly efficient methods have been developed for their production. − One of them is the Cu-catalyzed cross-coupling of asymmetry substituted indole (Scheme a) . By means of organocatalysis, Huo et al developed a synthetic method to generate DIMs from sodium triphenylphosphine- m -sulfonate (TPPMS) and CBr 4 (Scheme b).…”

“…However, our system provides excellent selectivity for 4a , b . Nonetheless, when HCl was used, the yields of 4a and 4b become 37 and 53%, respectively, with two side products …”

“…Nonetheless, when HCl was used, the yields of 4a and 4b become 37 and 53%, respectively, with two side products. 13 Compared with the ketones that are less reactive, the aldehydes show much higher efficiency. No matter whether an electron-donating or an electron-withdrawing group is attached on the aromatic rings (e.g., methoxy, bromine, chlorine), the aldehydes readily give DIMs in good yield under an air atmosphere (5a−e, 76−89%) (Scheme 5).…”

Molecular-iodine catalyzed selective construction of cyclopenta[b]indoles from indoles and acetone: a green gateway to indole-fused cycles

“…The initial synthesis of cyclopenta[ b ]indole by reacting indole and acetone under strong acidic conditions of ethanolic HCl or trifluoroacetic acid and its structural determination were reported in 1989 by Bergman et al 25 Subsequently, a few studies using mineral and Lewis acidic conditions were disclosed. 26–28 However, most of the reaction conditions are toxic and corrosive in nature, causing handling and disposal problems. Also, the reaction between indole and acetone under strong acidic conditions has proved to be complex in nature due to the possibility of the formation of a wide variety of products.…”