Level 1 – Case 2
8
Experimental Data
The second sulfenylation of 3-(phenylthio)indole 3 with methanesulfenyl chloride
yields a mixture of the bis-sulfides 4 and 5 (Scheme 2.3).
N
H
SPh
MeSCl
N
H
SPh
SMe
N
H
SMe
SPh
3
4
5
Scheme 2.3
When compound 6 was treated with benzenesulfenyl chloride at room temperature, 2,3-bis-phenylthioindole 7 was formed (Scheme 2.4). The reaction needs at
least a full equivalent of sulfenyl chloride to go to completion.
N
SPh
SPh
N
H
SPh
SPh
PhSCl
6
7
Scheme 2.4
Discussion
For a start, the simplest option is to consider the mechanism of direct introduction
of the sulfenyl group into the 2-position (Scheme 2.5). The nucleophilic attack of
the indole nucleus to the sulfenyl chloride requires a temporary disruption of the
aromaticity of the ring system leading to intermediate 8, which after aromatization
leads to the final product 2.
N
H
SR
RS-Cl
Cl
N
H
SR
SR
1
8
2
N
H
H
SR
SR
Scheme 2.5
Although reasonable, this mechanism cannot explain the mixture of isomers obtained in the sulfenylation of 3-(phenylthio)indole 3 with methanesulfenyl chloride. As represented in Scheme 2.6, under these conditions, 3 should exclusively
yield bis-sulfide 4. The direct sulfenylation at the 2-position of the indole ring
should be thereafter discarded.