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.
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