indole to 4-bromoindole

mk-1 · Wed Jun 15, 2005 9:20 pm

hello dear bees.
Ive been pondering about the reaction between indole and the selective brominating agent NBS (N-bromo-Succinimide). Is it possible it will react with the indole and add a bromine atom to the 4-position only? or maybe the use of oxone/KBr will work well?
what about doing the same reaction on 3-substituted indoles? like gramine or N-Methyltryptamine... anyone has any insights?

Im sorry if this threads goes to the tryptamine forum, but I posted it here since it seems to me it is less tryptamine direct and more advanced organic chemistry directed... Mods, feel free to move it to the tryptamine forum if u find it relevent.

EDIT :
Im aware of available easy synthesis of 4-bromoindole from easily acuired precurors, but that is not my quesitons. ill put one up here just for reference :

4-Bromoindole

A mixture of 2-bromo-6-nitrotoluene (100 g, 460 mmol), dimethylformamide-dimethyl acetal (184 ml, 1.38 mmol) and pyrrolidine (39 ml, 460 mmol) in DMF (1 l), was heated at 110°C for 3 h. The cooled mixture was poured into a 1 : 1 mixture of ice and water (1.5 l) and extracted with diisopropyl ether (3 x 1000 ml) until little red colour remained in the aqueous layer. Solvent removal in vacuo gave the intermediate 1-(N,N-dimethyl)-2-(2-bromo-6-nitrophenyl)ethenylamine (120 g).
This (5.4 g, 20 mmol) , in methanol, (50 ml), was added dropwise to a mixture of titanium trichloride (10% solution in 20-30% hydrochloric acid, 120 ml, 77 mmol) and aqueous ammonium acetate (4 M. 240 ml, 960 mmol) in a 1 l. dropping funnel and the mixture shaken vigorously for 10 min. Dilute hydrochloric acid (10%, 25 ml) was added to the mixture which was then extracted with diisopropyl ether (2 x 200 ml). The combined organic extracts were washed with water (250 ml), dried (MgSO4) and concentrated in vacuo to give a brown oil which was purified by column chromatography (SiO2, 3:1 hexane:dichloromethane). 4-Bromoindole was obtained as a yellow oil, (2.9 g, 71%) b.p. 91-93°C/0.5 mmHg (lit.22 96°C/1.0 mmHg), i.r. (film)/cm-1 3415, 1620, 1615, 1570, 1430, 1340, 1175, 890, 755; p.m.r. (CDCl3) 6.59 (1H, m), 7.01 (2H, m), 7.09 (1H, m), 7.19 (1H, m), 8.18 (1H, br s, ).
refs :
Metal-halogen exchange of bromoindoles. A route to substituted indoles
Mikel P. Moyer, John F. Shiurba, and Henry Rapoport
J. Org. Chem. 1986,51, 5106-5110.
original article pdf link, though it costs money