Hydrochloric Acid → Phenol, 2-chloro-3-nitro-

Temperature

0 °C

2-Amino-3-nitrophenol 2B1 (5 g; 32.4 mmol) was dissolved in concentrated HCl (75 mL) and 1,4-dioxane (14.7 mL). The mixture was heated to 70C until most of the solids were in solution. The reaction mixture was cooled to 0° C. (ice bath), and sodium nitrite (2.23 g; 32.3 mmol) in H2O (5.4 mL) was added over a period of 3 hours to the brown solution. The temperature was maintained below 10C during the addition and the stirring was continued for an additional 15 min. at 0° C. This diazonium intermediate was poured into a solution of Cu(I)Cl (3.8 g; 38.9 mmol) in H2O (18.5 mL) and conc. HCl (18.5 mL) at 0° C. The reaction was stirred for 15 min. at 0° C., warmed to 60° C., and stirred for an additional 15 min. The reaction mixture was then brought to room temperature, and left to stir overnight. The reaction mixture was transferred to a separatory funnel and extracted with ether (3×150 mL). The organic layers were combined, washed with brine (1×), dried (Na2SO4), filtered and concentrated to afford the crude product (5.83 g) as a red-brown oil. The crude material was purified by flash column chromatography (1:25 ultra pure silica gel, 230-400 mesh, 40-60 mm, 60 angstroms; 3:1 hexane/EtOAc as the solvent) to afford pure 2-chloro-3-nitrophenol 2C1 (48%; 2.7 g) as an orange solid. MS 171.8 (MH)−: Homogeneity by HPLC (TFA) @ 220 nm: 96%.

1. additionwas added over a period of 3 hours to the brown solution
2. temperaturewarmed to 60° C.
3. stirringstirred for an additional 15 min
4. customwas then brought to room temperature
5. waitleft
6. stirringto stir overnight
7. customThe reaction mixture was transferred to a separatory funnel
8. extractionextracted with ether (3×150 mL)
9. washwashed with brine (1×)
10. dry with materialdried (Na2SO4)
11. filtrationfiltered
12. concentrationconcentrated
13. customto afford the crude product (5.83 g) as a red-brown oil
14. customThe crude material was purified by flash column chromatography (1:25 ultra pure silica gel, 230-400 mesh, 40-60 mm, 60 angstroms

ORD record

ord-bc8e1b1fe79642999c4fe159e6982dbe

Source dataset

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07749961B2