General procedure for the synthesis of 2-iodo-5-chlorotoluene from 3-chlorotoluene: 3-chlorotoluene (1 mmol) was dissolved in dichloromethane (3 mL) and the corresponding silver salt (0.32 g, 1 mmol) and iodine (0.25 g, 1 mmol) were added. The reaction mixture was stirred at room temperature for 16 hours. Upon completion of the reaction, the reaction mixture was cooled with ice-cold water and the reaction was quenched by the addition of aqueous sodium metabisulfite (0.2 mL), or in the case of aniline compounds, 2M NaOH (0.2 mL). The reaction mixture was filtered through Celite and the residue was washed with dichloromethane (3 x 3 mL). The combined filtrates were washed sequentially with aqueous sodium bicarbonate (3 mL), water (3 mL) and brine (3 mL). The organic phase was dried with anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. The residue was redissolved in dichloromethane (10 mL) and the conversion of the feedstock and the yield of the iodide product were determined by GC-MS using diethylene glycol di-n-butyl ether as an internal standard. The relative response factor (RRFA) of the analytes was calculated using the formula RRFA = AIS × MA / (AA × MIS), where AIS is the peak area of the internal standard, AA is the peak area of the analyte (feedstock or iodide product), MA is the mass of the analyte, and MIS is the mass of the internal standard. The mass of the analyte in the reaction mixture was calculated by MA = (RRFA × MIS × AA) / AIS. All samples were analyzed at least twice in parallel. For selected reactions, the iodide products were separated by column chromatography to obtain milligram scale products for characterization and analytical standards. The amount of product obtained by separation was not sufficient for 13C NMR analysis in the 3 g scale reaction.
