Indoles 87a Friedel–Crafts catalyst: 3-acetylation simply requires heating with acetic anhydride; trifl uoroacetylation proceeds
even at 0 °C and this product can be simply hydrolysed to the corresponding acid, or converted into a 3-carboxamide,
as indicated.
Sulfur substituents can also be introduced via electrophilic substitution: sulfonation uses the pyridine-sulfur trioxide
complex; sulfenylation is achieved with a sulfenyl halide (often conveniently generated in situ).
Easy substitution at the -position is illustrated by the mild intramolecular Mannich reaction involved in the conver-
sion of tryptamine, via an electrophilic iminium intermediate, into a 1,2,3,4-tetrahydro--carboline (-carboline is
the widely used, trivial name for pyrido[3,4-b]indole).
Electrophilic substitutions of indoles are widely used – three other illustrative examples, from many, are: (i) alkylation
with nitroethene, again without any acid or other catalyst being required, (ii) conversion into a 3-aldehyde via the
Vilsmeier reaction, and (iii) Mannich substitution forming a 3-dialkylaminomethylindole (‘gramine’ from indole itself,
formaldehyde and dimethylamine), involving attack by a mild iminium electrophile, [H 2 C=NR 2 ], all illustrating again
selectivity for the -position.