The general procedure for the synthesis of 4-iodo-2-methylanisole from 2-methylanisole is as follows: to a stirred solution of 2-methylanisole (1 mmol) in dichloromethane (CH2Cl2) or 1,2-dichloroethane ((CH2Cl)2) (0.1 M), triphenylphosphorane-gold bis(trifluoromethylsulfonyl)imide (Ph3PAuNTf2) (0.025 mmol , 19 mg; if toluene-coordinated Ph3PAuNTf2 complex was used, the ratio was 2:1), followed by the addition of N-iodosuccinimide (NIS) (1.1 mmol, 248 mg). The reaction mixture was stirred at room temperature or reacted under reflux conditions until complete conversion of the feedstock was confirmed by thin layer chromatography (TLC) monitoring. Upon completion of the reaction, the solvent was evaporated under reduced pressure and the resulting crude product was purified by fast column chromatography using different ratios of hexane and ethyl acetate (EtOAc) as eluents to finally obtain pure 4-iodo-2-methylanisole.
[1] Synthetic Communications, 2003, vol. 33, # 8, p. 1319 - 1323
[2] Chemistry Letters, 1988, # 5, p. 795 - 798
[3] Synlett, 2014, vol. 25, # 3, p. 399 - 402
[4] Tetrahedron Letters, 1996, vol. 37, # 23, p. 4081 - 4084
[5] Journal of Organic Chemistry, 2006, vol. 71, # 11, p. 4349 - 4352
