3-BROMO-4-CHLOROANILINE

A suspension of 3-bromo-4-chloronitrobenzene (2.5 g, 10.6 mmol) and tin chloride dihydrate (12.0 g, 52.9 mmol) (Keana, J. F. W. et al J. Med. Chem. 1995, 38, 4367-4379) in EtOAc (38 ml) and EtOH (19 ml) was stirred at 70°C for 1 hr. The resulting solution was added to crushed ice and was carefully neutralized with Na2C03. The suspension was then extracted with EtOAc three times. The combined organic layers were concentrated to give the title compound (2.14 g, 99percent). NMR (CDC13) 8 3.70 (br s, 2 H), 6.55 (m, 1 H), 6.90 (s, 1 H), 7.18 (m, 1 H).To a solution of 2-bromo-l-chloro-4-nitro-benzene (30.0 g, 127 mmol) in ethanol (300 mL)/HGeneral procedure: A round-bottomed flask (25 mL) was charged with substrate (2 mmol), CuClTo a precooled (0 C) solution of To a precooled (0 C) solution of To a precooled (0 C) solution of General procedure: A dry, 50 mL round bottom flask was charged with a magnetic stir bar then sealed with a septum and flushed with nitrogen. To this was added the salicylic acid derivative (2.0 mmol) and dichloromethane (10 mL). While stirring, SOCl2 (10 mmol) was added dropwise, followed by dimethylformamide (0.05 mmol), and the mixture was allowed to stir at room temperature under nitrogen for 12 hours. At this point, the mixture was concentrated under vacuum to afford the solid acid chloride derivative which was used immediately without further purification. The flask containing the acid chloride was then re-sealed with a septum and placed under a nitrogen atmosphere, and its contents were re-suspended in fresh dichloromethane (20 mL). While stirring, the aniline derivative (4.0 mmol) was added and the resulting opaque mixture was stirred for an additional 18 h. At this point, the mixture was quenched with ice water (5 mL) and phases were separated using a separatory funnel. The aqueous layer was extracted twice with dichloromethane (20 mL) then the organic layers were combined and washed with brine (40 mL). The organic layer was then dried over Na2SO4, filtered, and concentrated under vacuum to afford a crude solid residue. This residue was then re-suspended in dichloromethane (10 mL) and adsorbed onto silica gel (1 g), then chromatographed on a 12 g silica gel column using a solvent gradient of 0-40% ethyl acetate in hexanes over 25 min. The product-containing fractions were combined then concentrated under vacuum to afford the purified salicylamide derivative.

Molecular Weight:206.47
XLogP3:2.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:204.92939
Monoisotopic Mass:204.92939
Topological Polar Surface Area:26
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes