2-Bromo-6-methylaniline

Uses

2-Bromo-6-methylaniline can be used as a reactant to synthesize:

• Alkyl substituted bromoindazole building blocks by Pd-catalyzed Suzuki coupling reaction with various vinyl boronic acids.
• Difluoropyridoindole via Pd-catalyzed intramolecular Heck reaction with difluoropiperidinone.
• 4-Methyl-N-phenyl-1H-benzo[d]imidazol-2-amine by one-pot Cu-catalyzed domino C-N cross-coupling reaction with iodobenzene and thiourea.

Synthesis

The general procedure for the synthesis of 2-bromo-6-methylaniline from 3-bromo-2-nitrotoluene was as follows: tellurium (21.6 g, 169.4 mmol) and sodium borohydride (15.0 g, 396 mmol) were dissolved in 575 mL of anhydrous ethanol under the protection of nitrogen, heated and refluxed for 1 h and then cooled to room temperature. Subsequently, a solution of 3-bromo-2-nitrotoluene (7.32 g, 33.8 mmol) dissolved in 25 mL of ethanol was added all at once and the reaction mixture was stirred for 2 hours at room temperature. After completion of the reaction, the reaction mixture was filtered through diatomaceous earth (CELITE). The filtrate was evaporated under reduced pressure and the residue was dissolved in about 200 mL of ether, washed with saturated brine and dried over anhydrous magnesium sulfate. Finally, the solvent was evaporated to give 2.66 g (42% yield) of 2-bromo-6-methylaniline as a dark liquid.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 11, p. 3177 - 3180
[2] Patent: US2004/110815, 2004, A1. Location in patent: Page/Page column 18
[3] Patent: WO2005/16892, 2005, A1. Location in patent: Page/Page column 68
[4] Chemische Berichte, 1937, vol. 70, p. 2427,2430
[5] Yakugaku Zasshi, 1837, vol. 58, p. 1,7