Level 1– Case 2
Sulfenylation of Indole
Key point: Structure of products and mechanism
N
H
SR
N
H
SR
SR
RSCl
Sulfenylation of Indole
3-Indolyl sulfides 1 are easily prepared by sulfenylation of indoles with sulfenyl
chlorides. The mechanism of the sulfenylation is well known and follows the
usual S E Ar-type substitution pathway depicted in Scheme 2.1.
N
H
RS-Cl
N
H
SR
H
Cl
N
H
SR
1
Scheme 2.1
One drawback to the use of sulfenyl chlorides for the sulfenylation of indoles is
their exceptional reactivity. If the 2-position of the indole is unoccupied, the
slightest excess of reagent leads to a second sulfenylation, and a full second
equivalent leads to excellent yields of 2,3-indolyl bis-sulfides 2 (Scheme 2.2).
N
H
SR
N
H
SR
SR
RSCl
Scheme 2.2
The question to be resolved is the following: is the second sulfide group introduced directly at the 2-position of the indole ring or is it necessary to consider an
alternative mechanism for the formation of bis-sulfides 2?
Sulfenylation of Indole
Key point: Structure of products and mechanism
N
H
SR
N
H
SR
SR
RSCl
Sulfenylation of Indole
3-Indolyl sulfides 1 are easily prepared by sulfenylation of indoles with sulfenyl
chlorides. The mechanism of the sulfenylation is well known and follows the
usual S E Ar-type substitution pathway depicted in Scheme 2.1.
N
H
RS-Cl
N
H
SR
H
Cl
N
H
SR
1
Scheme 2.1
One drawback to the use of sulfenyl chlorides for the sulfenylation of indoles is
their exceptional reactivity. If the 2-position of the indole is unoccupied, the
slightest excess of reagent leads to a second sulfenylation, and a full second
equivalent leads to excellent yields of 2,3-indolyl bis-sulfides 2 (Scheme 2.2).
N
H
SR
N
H
SR
SR
RSCl
Scheme 2.2
The question to be resolved is the following: is the second sulfide group introduced directly at the 2-position of the indole ring or is it necessary to consider an
alternative mechanism for the formation of bis-sulfides 2?