Iodoethane → 1-Ethyl-3-methyl-1H-indole-5-carboxaldehyde

Participants

Reaction Conditions

Reaction Steps

Into a 2000 milliliter 3 neck flask equipped with a magnetic stirring bar, a thermometer and a nitrogen inlet tube are introduced 400 milliliters anhydrous dimethylformamide, 220 milliliters anhydrous ethylether and 29.36 grams (0.22 moles) 3-methylindolyl (available from Aldrich Chemical Company). After the contents of this flask are thoroughly combined, about 64.84 grams (0.26 moles) thallous ethoxide are added to the solution, and the flask thereafter heated to 40° C with stirring for about 60 minutes during which time the reaction mixture takes on a metallic appearance. At the end of this interval, 41.33 grams (0.26 moles) ethyliodide is introduced into the flask whereupon precipitation of orange colored particulates takes place. The reaction mass is heated to a temperature of about 50° - 5° C with constant agitation for an additional 3 hours, cooled and the solids separated from the reaction mass by filtration. The filtrate is diluted with water and separates into 2 distinct phases; the ether phase being set aside and the aqueous phase being extracted several times with chloroform. All organic layers are then recombined and extracted several times with water to remove residual traces of dimethylformamide. The ether phase is now dried over anhydrous magnesium sulfate and evaporated to an oily residue. This residue is distilled at 80° C (0.2 mm) and the fraction collected at this temperature analyzed and found to be N-ethyl-3-methylindole. Into a 3 neck 250 milliliter round bottom flask equipped with a nitrogen inlet tube, a magnetic stirring bar and a thermometer are placed 17.47 milliliters dimethyformamide. The flask and its contents are cooled in an ice bath and 21.29 milliliters of POC13 added by dropwise addition. The flask is now transferred to a room temperature oil bath and 36.6 grams (0.23 moles) N-ethyl-3-methylindole in 25 milliliters dimethylformamide added by dropwise addition. The reaction of these materials is highly exothermic and the temperature of the bath is maintained at 40° C during the combination of these materials and the reaction allowed to proceed for an additional 3 hours at this temperature. At the end of this period, the reaction mixture is poured into about 1 liter of water with stirring, and the resulting solution titrated with sodiumhydroxide until slightly basic (approximately 7 milliliters base added to this solution). An oily residue product which forms is extracted with chloroform, the chloroform evaporated and the product purified by vacuum distillation; yield is approximately 50 percent.

Provenance & Evidence