Indole → 6,7-DIMETHYLINDOLE

Participants

Reaction Steps

To a solution of boron trichloride (200 mL of 1M in xylene; 200 mmol) at 0°-5° C. was added 2,3-dimethylaniline (22.2 mL, 182 mmol) in dry toluene (110 mL) dropwise over 20 minutes, followed by 2-chloroacetonitrile (13.8 mL, 218 mmol) dropwise over 10 minutes, and finally AlCl3 (27.0 g, 202 mmol) in one portion. The mixture was heated to reflux for 1 hour and 80° C. for 16 hours before cooling and addition of 2N HCl (190 ml). The mixture was heated to 80° C. for 30 min, cooled to 20° C., and the pH adjusted to 3-4 with 2N NaOH. The mixture was extracted with CH2Cl2 with readjustment of the pH to 3-4 after each extraction. The organic extracts were pooled, washed with brine, dried over Na2SO4(s), filtered and concentrated in vacuo. The residue (28.9 g) was recrystallized from CHCl3 /hexanes to afford 26.1 g of pure 2-amino-3,4-dimethyl-α-chloroacetophenone (GC-MS: 197 (M+)). This chloromethylketone (5.02 g, 25.4 mmol) in dioxane (125 mL)/H2O (15 mL) was treated with NaBH4 (1.06 g, 28 mmol) and heated to reflux for 4 hours. The mixture was concentrated in vacuo and partitioned between H2O/CH2Cl at pH ~7. The organic extracts were pooled, dried over MgSO4(s), filtered and concentrated in vacuo to afford the crude indole product (2.9 g) which could be reduced directly or sublimed in vacuo to afford 1.55 g of the title compound so pure indole (GC-MS; 145 (M+)).

Provenance & Evidence