The reaction mechanism of the Bartoli indole synthesis is illustrated below using o-nitrotoluene (
1) and propenyl Grignard (
2) to form 3,7-dimethylindole (
13). The mechanism begins by the addition of the Grignard reagent (
2) onto the nitroarene (
1) to form intermediate
3. Intermediate
3 spontaneously decomposes to form a
nitrosoarene (
4) and a
magnesium salt (
5). (Upon reaction workup, the magnesium salt will liberate a
carbonyl compound (
6).) Reaction of the nitrosoarene (
4) with a second equivalent of the Grignard reagent (
2) forms intermediate
7. The steric bulk of the ortho group causes a sigmatropic rearrangement|[3,3]-sigmatropic rearrangement forming the intermediate
8. Cyclization and
tautomerization give intermediate
10, which will react with a third equivalent of the Grignard reagent (
2) to give a dimagnesium indole salt (
12). Reaction workup eliminates
water and gives the final desired indole (
13). Therefore, three equivalents of the Grignard reagent are necessary, as one equivalent becomes carbonyl compound
6, one equivalent deprotonates
10 forming an
alkene (
11), and one equivalent gets incorporated into the indole ring. The nitroso intermediate (
4) has been isolated from the reaction. Additionally, reaction of the nitroso intermediate (
4) with two equivalents of the Grignard reagent produces the expected indole. The scope of the reaction includes substituted pyridines which can be used to make 4-azaindoles(left) and 6-azaindoles(right). ==Variations==