Benzene, 4-chloro-1-methyl-2-nitro- → 6-Chloroindole

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Reaction Conditions

Reaction Steps

A mixture of 4-chloro-2-nitrotoluene (34 g, 0.2 mole), dimethylformamide dimethyl acetal (28 mL, 0.2 mole) and pyrrolidine (25 mL 0.3 mole) in dimethylformamide (DMF) is heated at 100° C. for 72 h, cooled to room temperature and concentrated in vacuo to give a deep red residue. The residue is taken up in methanol/tetrahydro-furan (1:1), treated with about 2 mL of a Raney nickel slurry and hydrogenated at atmospheric pressure. The reaction is monitored by GC, TLC and H2 uptake. After 2 hours, the hydrogenation is continued at 20 psi-40 psi for a total hydrogenation time of 24 hours. The resultant reaction mixture is filtered through diatomaceous earth. The filtercake is washed with methylene chloride and the combined filtrate is washed sequentially with 1 N HCl and saturated NaHCO3, dried over MgSO4 and concentrated in vacuo to give a brown oil residue. The residue is crystallized in hexanes to give the title product as a brown solid, 22 g (72.6 % yield), identified by IR, 1HNMR, 13CNMR and mass spectral analyses.

Provenance & Evidence