2,3,3-Trimethylindole (Alfa Aesar)

Sulphuric acid (Fisher Scientific)

Nitric Acid (Fisher Scientific)

To a 250 mL wide necked conical flask* was added 2,3,3-trimethylindole (12.42 g, 78 mmol) and concentrated sulphuric acid (46 mL).  The solution was transferred to an ice bath and with constant string a pre-cooled mixture of concentrated sulphuric acid (7 mL) and concentrated nitric acid (9.4 mL, 0.23 mol) was added dropwise via a dropping funnel. Upon total addition of the acidic mixture, the reaction was allowed to stir at room temperature for 3 hours. The reaction mixture was then poured over ice (approx. 500 g) which yielded a red precipitate.  Upon standing overnight, the pH was then adjusted to pH=8, via the slow addition of sodium hydroxide pellets** and the precipitate produced unpon neutralisation was isolated by vacuum filtration and washed with deionised water (500 mL). The solid was dissolved in a minimum amount of hot methanol, filtered*** and evaporated to dryness  to afford 2,3,3-trimethyl-5-nitro-indole (11.93 g, 78%) as a red solid**** 

*A conical flat bottomed flask fitted with a dropping funnel was used.  Stirring was accomplished using a stirring bar, which was controlled from the hot plate.  The whole reaction was accomplished in the open air without the need of dry/inert conditions.

** Universal indicator paper was used to monitor the change in pH to pH=7.

*** Filtration was used to remove any impurities.

**** The red solid can be can be recrystallised to give a pure compound, however we wanted to reduce the nitro to the amine and were happy to proceed with the crude NMR which is shown with minor impurities.

¹H-NMR (300 MHz, Chloroform-d): δ 8.25 (dd, J = 8.5, 2.2 Hz, 1H, Ar-H), 8.16 (d, J = 2.1 Hz, 1H, Ar-H), 7.61 (d, J = 8.5 Hz, 1H, Ar-H), 2.36 (s, 3H, C-CH₃) 1.37 (s, 6H, 2C-CH₃). ¹³C-NMR (300 MHz, Chloroform-d): δ 194.24, 158.95, 146.69, 145.61, 124.56, 120.05, 117.19, 54.51, 22.74, 16.02. IR (ATR): 2977, 1565, 1515, 1420, 1389, 1333, 1206, 1112, 1056, 916, 847, 803, 738. GC-MS (EI) m/z: 91.02, 114.98, 143.05, 189.00, 204.05 ([M-H]⁺).

Santos, P.F., Reis, L.V., Duarte, I., Serrano, J.P., Almeida, P., Oliveira, A.S., Ferreira, L.F.V. Synthesis and photochemical evaluation of iodinated squarylium cyanine dyes (2005) Helvetica Chimica Acta, 88 (5), pp. 1135-1143.