1-Bromo-2,6-diisopropylbenzene can be purchased from chemical vendors. However, it can be quite expensive when bought in quantities larger than 10g, which is why I prefer to make it from 2,6-diisopropylaniline. The procedure involves a one-pot, two-step sequence, starting with formation of the anilinium bromide salt, followed by generation of the aryl diazonium salt which is quenched by bromide ions in solution.[1]
To a 500mL round-bottom flask was added 48% aqueous hydrobromic acid (150mL). Under vigorous stirring, 2,6-diisopropylaniline (30g, 169mmol) was poured into the solution, leading to rapid precipitation of the aniline hydrobromide salt. The suspension was subsequently cooled to c.a. -50degC (dry ice in 1:1 ethylene glycol : absolute ethanol cooling bath), and solid sodium nitrite (20g, 289mmol) was added gradually over the course of ten minutes. After stirring at -50degC for one hour, then precooled ether (60mL) was added, and the mixture was allowed to warm up to -15degC, which caused the evolution of brown fumes. Once the gas evolution slowed down, the mixture was cooled back to -50degC. Water (20mL) and sodium carbonate (100g) were added, allowing the mixture to slowly thaw to room temperature and stir overnight. The mixture was then extracted with diethyl ether (2 x 150mL), the organic layers combined, and subsequently dried with MgSO4. Ether was removed in vacuo and the crude product purified via vacuum distillation (0.001Torr, 65degC), yielding the product as a pale yellow oil (71%, 29.0g, 119mmol).
Notes
- All steps were done in air. Contrary to many literature procedures, I found no inert atmosphere was necessary.
- This is a copperless version of the Sandmeyer reaction.
- First step involves formation and precipitation of 2,6-diisopropylanilinium bromide. Cooling mixture and addition of NaNO2 leads to formation of nitrous acid (HNO2) and NaBr. This is the first reason why acid is added in excess.
- Nitrous acid further reacts with HBr forming the strongly electrophilic nitrosonium ion after dehydration. This is the second reason why acid is added in excess. Nitrosonium reacts with anilines to form diazonium salts, which must be kept cold to prevent decomposition. Unreacted nitrous acid decomposes to NO2 upon warming to -15degC, as evidenced by the evolution of brown fumes.
- Look out for a blueish tinge in the reaction, which is evidence of nitrous acid being formed.
- Bromide anions from NaBr byproduct react with diazonium salt to form the product, concomitantly extruding N2 in the process. Acidic reaction medium is ultimately quenched/neutralized with sodium carbonate.
[1] Wallasch, M. W.; Weismann, D.; Riehn, C.; Ambrus, S.; Wolmershäuser, G.; Lagutschenkov, A.; Niedner-Schatteburg, G.; Sitzmann, H. Organometallics 2010, 29, 4, 806-813.