Novel, Practical, and Efficient Process for the Preparation of 4,5-Dichloroindole

A novel, practical, and efficient three-step process for the preparation of 4,5-dichloroindole 5, an important starting material for a wide range of fine chemicals and pharmaceuticals has been developed. The process comprises nitration of commercially available 2,3-dichlorobenzaldehyde 1, a telescopic process for the Henry reaction, and subsequently reductive cyclization of resulting o,β-dinitrostyrene intermediate 4 into 4,5-dichloroindole using iron powder in methanol and acetic acid by the Nenitzescu reaction. The large-scale applicability of this novel and improved process has been successfully demonstrated on a multikilogram scale by carrying multiple batches to produce 5 in 67–70% yields and 96–98% purity without column chromatography. The reactions are facile, safe, and easy to scale up.