The synthesis of some 3‐acylindoles revisited

Abstract

A study probing the scope of acylation of indoles with dicarboxylic acids in acetic anhydride has been performed, resulting in products incorporating 3‐acylindole‐ or 1‐acylindole motifs depending on the choice of the acid reactant. Synthetically useful results were only obtained from reactions involving malonic acid or Meldrum's acid. Correlations to previous studies have also been made and discussed.

Synthesis of New (E)-2-(1H-Indole-3-ylcarbonyl)-3-heteroaryl-acrylonitriles via Microwave-Assisted Knoevenagel Condensation

“…The entire carbon skeleton was assigned by 13 C-NMR spectra. Notice that all the compounds synthesized retain signals similar to the cyanoacetylindole skeleton, similar to those reported previously [68,69] as well as a typical NH absorption in the IR spectrum (]; 3,400-3,300 cm −1 ).…”

Discovery of cis-N-(1-(4-(Methylamino)cyclohexyl)indolin-6-yl)thiophene-2-carboximidamide: A 1,6-Disubstituted Indoline Derivative as a Highly Selective Inhibitor of Human Neuronal Nitric Oxide Synthase (nNOS) without Any Cardiovascular Liabilities

“…22 Reduction of the nitro group under transfer hydrogenation conditions, followed by coupling with thiophene-2-carbimidothioate 13, 23 gave the target compounds 14−16. The N-alkylation of 6 with 2-chloroacetyl chloride 24 provided chloro intermediate 17, which was substituted with two different amines under basic conditions to obtain 18 and 19, respectively (Scheme 2). The secondary amine in 19 was protected as tert-butyl carbamate to obtain 20.…”

“…1 21) (1.24 g, 4.47 mmol) as described for 14 to obtain the title compound (0.113 g, 7%) as a solid. 1 H NMR (DMSO-d 6 ) δ 7.70 (dd, 1H, J = 0.9, 3.6 Hz), 7.58 (dd, 1H, J = 0.6, 5.1 Hz), 7.07 (dd, 1H, J = 3.6, 5.1 Hz), 6 (24). Prepared from tert-butyl 2-hydroxyethyl(2-(6-nitroindolin-1-yl)ethyl)carbamate (22) (0.89 g, 2.53 mmol) as described for 14 to obtain the title compound (0.57 g, 53%) as a yellow solid.…”

Chemistry of 3-(2-Haloacyl)indoles

“…However, It is well established that heating of indole with chloroacetyl chloride in toluene gives 1-chloroacetylindole (10a), [57] which has previously also been obtained from the reaction of indole with chloroacetic anhydride in refluxing dioxane. [58] Therefore, Bergman and co-workers [59] were rather surprised to learn that Elnagdi and co-workers claim preparation of 3-chloroacetylindole (1b) by heating indole with chloroacetyl chloride in refluxing dioxane. However, the reported melting point of the resulting product (mp.…”

“…[95] Moreover, refluxing (1b) with ethyl S-benzyl-L-cysteinate (109) in ethanol containing a catalytic amount of triethylamine afforded (110) in 24% yield (Scheme 32). [95] Reaction with ammonium thiocyanate and potassium cyanide Treatment of 3-chloroacetylindole (1b) with ammonium thiocyanate in acetonitrile [56] at 50 º C or in the presence of catalytic amount of tetrabutylammonium iodide [59] afforded 2-(1H-indol-3-yl)-2-oxoethyl thiocyanate (111) in good yield. Elnagdi and co-workers [56] claim preparation of 3-(1H-indol-3-yl)-3-oxopropanenitrile (112) in 95% yield by treatment of (1b) with potassium cyanide in benzene (Scheme 33).…”