Answer to Question #18043 in Organic Chemistry for Sean

Question

I wanted to figure out how to attach a carbonyl group (either from an aldehyde or carboxylic acid) to the 3-position of indole. I may use a carboxy chloride. Since indole has 2 aromatic rings, there are several carbons available for attachment, and the carbonyl group might randomly become attached to any one of them, from what I understand. So my question pertains to specificity. How do I make sure it specifically attaches to the 3-position?

Answer 1

Indole is a π-excessive heterocycle, therefore it is subjected to ready electrophilic substitution and C₃ is the preferred site for electrophilic attack.