Heterocyclic Chemistry at a Glance

98 Indoles

Like indole, they undergo electrophilic substitution in the fi ve-membered ring but have the advantage of not being as
acid-sensitive as indole. Nucleophilic substitution can be carried out in the six-membered ring, with a reactivity similar
to the corresponding chloropyridines (much less reactive than chloro-(iso)quinolines).

Exercises

1. What are the structures of the intermediates and fi nal product in the following sequence: indole with
   (COCl) 2 → C 10 H 6 ClNO 2 then this with ammonia → C 10 H 8 N 2 O 2 then this with LiAlH 4 → C 10 H 12 N 2?


2. Deduce a structure, and write out the mechanism for the conversion of 2-formylindole into a tricyclic com-
   pound, C 11 H 9 N, on treatment with a combination of NaH and Ph 3 PCH=CH 2 Br–.


3. What are the products formed in the following sequence: 3-iodoindole with LDA, then PhSO 2 Cl→
   C 14 H 10 INO 2 S, then this product with LDA, then I 2 → C 14 H 9 I 2 NO 2 S.


4. When 3-dimethylaminomethylindole is heated with NaCN, 3-cyanomethylindole (indol-3-yl-CH 2 CN) is
   formed. What is the mechanism?


5. When indol-3-yl-CH 2 OH is heated with acid, di(indol-3-yl)methane is formed: suggest a mechanism for
   this transformation.


6. Which phenylhydrazones would be required for the Fischer indole synthesis of: (i) 3-n-propylindole;
   (ii) 1,2,3,4-tetrahydro-6-methoxycarbazole; (iii) 2-ethyl-3-methylindole; and (iv) 3-ethyl-2-phenylindole?


7. What product, C 10 H 11 NO, would be obtained from refl uxing a mixture of phenylhydrazine and 2,3-dihydrofuran
   in acetic acid?


8. Heating DMFDMA with the following aromatic compounds led to condensation products; subsequent
   reduction with the reagent shown gave indoles. Draw the structures of the condensation products and the
   indoles: (i) 2,6-dinitrotoluene then TiCl 3 gave C 8 H 8 N 2 ; (ii) 2-benzyloxy-6-nitrotoluene then H 2 –Pt gave
   C 15 H 13 NO; (iii) 4-methoxy-2-nitrotoluene then H 2 –Pd gave C 9 H 9 NO; and (iv) 2,3-dinitro-1,4-dimethyl-
   benzene then H 2 –Pd gave C 10 H 8 N 2.


9. How could one convert 2-bromoaniline into 2-phenylindole (more than one step is required)?