2-CHLORO-3-IODOPHENOL

2-CHLORO-3-IODOPHENOL Property

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

Appearance

Light brown to brown Solid

Safety

HS Code 

2908190090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

2-CHLORO-3-IODOPHENOL Chemical Properties,Usage,Production

Synthesis

The general procedure for the synthesis of 2-chloro-3-iodophenol from 3-amino-2-chlorophenol is as follows: 1. To a suspension of 2-amino-3-nitrophenol (10 g, 65 mmol) in concentrated hydrochloric acid (10 mL) was added dropwise an aqueous solution of sodium nitrite (5.1 g, 73.3 mmol) (60 mL) at 0 °C. After stirring for 30 min, 10% H2SO4 solution (3 mL) of CuCl (12.8 g, 130 mmol) was added and stirring was continued for 18 hours. The reaction mixture was filtered, washed with water and the filtrate was extracted with EtOAc (70 mL x 3). The EtOAc layer was concentrated to give 2-chloro-3-nitrophenol (7 g, 62% yield). 2. 2-Chloro-3-nitrophenol (6 g, 35 mmol) was dissolved in methanol (100 mL), ammonium chloride (9.4 g, 175.7 mmol) and zinc powder (46 g, 702.8 mmol) were added, and refluxed for 1 hour. It was filtered and concentrated to give 2-chloro-3-aminophenol (4.5 g, 90% yield) as a purple solid. 3. To a suspension of 2-chloro-3-aminophenol (4.5 g, 31 mmol) in concentrated hydrochloric acid (10 mL) was added an aqueous solution of sodium nitrite (2.5 g, 35 mmol) (50 mL) dropwise at 0 °C. After stirring for 30 min, 10% H2SO4 solution (3 mL) of iodine (10.4 g, 63 mmol) was added and stirred for 2 h at room temperature. After filtration, it was extracted with EtOAc and concentrated to give 2-chloro-3-iodophenol (6 g, 75% yield) as a dark purple solid. 4. 6-Bromo-2,2,4-trimethyl-1,2-dihydroquinoline (2.3 g, 9.2 mmol) was mixed with bis(pinacolato)diborane (4.2 g, 16.5 mmol) in DMSO (2 mL) and KOAc (2.7 g, 27.4 mmol) and PdCl2 (dppf) (100 mg) were added. The reaction was carried out at 120°C for 15 min in microwave, cooled and purified by chromatography to afford 2,2,4-trimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroquinoline (2.3 g, 84% yield) as a white crystalline solid. 5. 2,2,4-Trimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2-dihydroquinoline (308 mg), 2-chloro-3-iodophenol (93 mg), PdCl2 (dppf) (100 mg) and KOAc (300 mg) were coupled to give 2-chloro-3-(2,2,4-trimethyl-1 ,2-dihydroquinolin-6-yl)phenol (85 mg). 6. The above product (85 mg) was reacted with NBS according to the method of Example 7 to obtain 3-(4-bromomethyl-2,2-dimethyl-1,2-dihydroquinolin-6-yl)-2-chlorophenol (56 mg). 7. Finally, the product (50 mg) was coupled with 2-phenylethanethiol (0.04 mL) to give the title compound (40 mg) as an oil.

References

[1] Patent: WO2004/18429, 2004, A2. Location in patent: Page 87