Indole → 1-Methylindole

Participants

Reaction Steps

The R group can be at any position of the indole system except position 1. The reaction between indole-3-carboxylic acids and dimethyl carbonate was also investigated. The selectivity between O-methylation and N-methylation was not as high as would be expected. However, as expected, under the reaction conditions, esterfication of a carboxyl group was somewhat faster than N-methylation. For example, the reaction of indole-3-propionic acid with dimethyl carbonate in the presence of potassium carbonate in OMF afforded both an O,N-dimethylated substance in 65% yield after 4 hours at refluxing temperature, together with 30% of the O-methylated product. After the reaction mixture was heated to reflux for another 4 hours, only O,N-dimethylated product was obtained in 93% isolated yield. As demonstrated in Table 2, similar results were observed with indole-3-acetic acid. But when indole-3-carboxylic acid was subjected to the typical reaction conditions, along with 50% of the dimethylated product obtained, 45% of N-methylindole was isolated, formed as a result of decarboxylation of indole-3-carboxylic acid at the reaction temperature (128° C.).

Provenance & Evidence