Iodine → N-(2'-Chloro-6'-methyl-phenyl)-4-ethylaniline

Participants

Reaction Conditions

Reaction Steps

A solution of 3.0 g 2-Chloro-6-methyl-aniline in 3.5 ml of tetrahydrofuran and 31 ml of chlorobenzene is cooled down to −40 to −45° C. At this temperature, 4.01 g of titanium-tetrachloride is added to the solution, followed by the addition of 6.18 g of 1-Methoxy-4-ethylcyclohexa-1,4-diene. The reaction mixture is allowed to warm up to approx. −35° C. and stirred for 3 hours at this temperature. A solution of 8.06 g of iodine in 16.4 ml of tetrahydrofuran and 1.8 ml of acetic acid is added to the reaction mixture and the temperature is allowed to warm up to 0° C. The mixture is stirred for 30 minutes at 0° C. and 2 hours at 25° C. Then 2.68 g of iodine is added to the reaction mixture and stirring is continued for additional 24 hours at 25° C. Again, 2.68 g of iodine is added and stirring is continued for additional 72 hours at 25° C. The reaction is finally quenched by pouring the reaction mixture onto a mixture of 250 ml of aqueous sodium bisulfite (38-40%) and 450 ml of saturated aqueous sodium carbonate. The water phase is extracted with ethyl acetate (1×200 ml and 2×100 ml), the ethyl acetate phases are unified and washed with 100 ml of brine. The organic phase was dried over anhydrous sodium sulfate and evaporated in vacuo to give a dark viscous liquid. The liquid was dissolved in heptane/toluene and the solution was filtered over silicagel to obtain, after evaporation of the solvent, 2.0 g of crude product. The product can be used directly in the next step. Alternatively, it can be purified e.g. by column chromatography on silica gel with heptane/toluene (7:3) as eluent to yield pure N-(2′-Chloro-6′-methyl-phenyl)-4-ethylaniline.

Provenance & Evidence