2-Bromo-6-chlorotoluene

Colorless liquid

2-Bromo-6-chlorotoluene serves as a precursor for (2-amino-5-bromophenyl)(3-chloro-2-methylphenyl)methanone: in anhydrous THF under dry nitrogen it is treated with n-BuLi at -78 °C to form an aryllithium in situ, which is then coupled with 2-amino-5-bromo-N-methoxy-N-methylbenzamide[1][3]. Under Cy3PAuCl catalysis with t-BuOK at 60 °C, 2-bromo-6-chlorotoluene reacts with pyridine to give 2-chloro-6-(2-pyridinyl)toluene selectively in 32% isolated yield[2].

[1] Kraus, J. M., Verlinde, C. L. M. J., Karimi, M., Lepesheva, G. I., Gelb, M. H., & Buckner, F. S. (2009). Rational Modification of a Candidate Cancer Drug for Use Against Chagas Disease. Journal of Medicinal Chemistry, 52(6), 1639–1647. https://doi.org/10.1021/jm801313t
[2] Li, M., & Hua, R. (2009). Gold(I)-catalyzed direct C–H arylation of pyrazine and pyridine with aryl bromides. Tetrahedron Letters, 50(13), 1478–1481. https://doi.org/10.1016/j.tetlet.2009.01.059
[3] Kraus, J. M., Tatipaka, H. B., McGuffin, S. A., Chennamaneni, N. K., Karimi, M., Arif, J., Verlinde, C. L. M. J., Buckner, F. S., & Gelb, M. H. (2010). Second Generation Analogues of the Cancer Drug Clinical Candidate Tipifarnib for Anti-Chagas Disease Drug Discovery. Journal of Medicinal Chemistry, 53(10), 3887–3898. https://doi.org/10.1021/jm9013136