SYNTHESIS OF INDOLE-3-CARBOXYLIC ACID AND INDOLE-3- METHANOL

ABSTRACT

Indole is considered the most privileged scaffold in heterocyclic chemistry with such broad applications as antiviral, antimicrobial, anti-inflammatory, anti-cancer, anti-hypertensive, anti-diabetic, and antioxidant due to its bioavailability and pharmacological applications. Very recently, it was reported that biological evaluation of indole-3-carbinol is under research because of its anticancer, antioxidant as well as antiatherogenic activities. The study is aimed at synthesizing indole-3-carboxylic acid and indole-3-carbinol. The starting material indole was used to synthesize indole-3-aldehyde via Vilsmeier Hack reaction (POCl3/DMF). Vilsmeier-Haack reagent was formed by adding drop by drop a freshly distilled phosphorus oxychloride (30ml) to 15g of Dimethylformamide (DMF) at 200C. Indole (11.5g) in DMF (4ml) was added slowly with stirring maintained at 20-300C. The mixture was raised to 350C for 45 minutes and then poured onto crushed ice and this solution was treated at 25-300C with an aqueous sodium hydroxide solution (10g) until strongly basic. Afterward the mixture was boiled for one minute, filtered, and resultant crystals of 3-formylindole washed with distilled water and dried giving the melting point of 197-1990C. 20% of NaOH was added to 3- formylindole under vigorous stirring and after 24hours a separation was observed in the reaction mixture which was filtered under vaccum, washed with distilled water and dried. The residue is the indole-3-carboxylic acid while the filtrate is the indole-3-methanol. The purity of the synthesized compounds were confirmed by determining the melting points and retention factor (Rf values) of the compounds and it shows that they are relatively pure with the exception of indole-3-carbaldehyde whose melting point range is above 20C which is due to impurities. Indole-3-carbaldehyde, indole-3-carboxylic acid and indole-3-methanol were successfully synthesized.