3-Fluoro-2-nitrophenol

3-Fluoro-2-nitrophenol Property

Melting point:

37-38°C

Boiling point:

237.6±20.0 °C(Predicted)

Density 

1.511±0.06 g/cm3(Predicted)

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

soluble in Methanol

form 

Solid

pka

3.56±0.10(Predicted)

color 

Light yellow to Brown

CAS DataBase Reference

385-01-3(CAS DataBase Reference)

Safety

Hazard Codes 

Xi,C

Risk Statements 

34

Safety Statements 

36/37/39-45

HazardClass 

IRRITANT

HS Code 

2908990000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P405Store locked up.

3-Fluoro-2-nitrophenol Chemical Properties,Usage,Production

Chemical Properties

Off-white crystalline

Synthesis

General procedure for the synthesis of 3-fluoro-2-nitrophenol from 2,6-difluoronitrobenzene: First, potassium TERT-butoxide (1.23 g, 11 mmol) was dissolved in 25 mL of anhydrous DMSO and stirred for 30 min at room temperature. Subsequently, 1,3-difluoro-2-nitrobenzene (1.59 g, 10 mmol) was added and the reaction was continued with stirring for 18 hours. After completion of the reaction, the mixture was diluted with 150 mL of aqueous 1N sulfuric acid and extracted with three 50 mL portions of diethyl ether. The organic layers were combined, washed with water, dried over sodium sulfate, filtered and concentrated in vacuum. The residue was dissolved in 50mL of trifluoroacetic acid and reacted for 30 minutes at room temperature before being concentrated again under vacuum. Next, the residue was treated with 50mL of 1N aqueous sodium hydroxide and extracted with three 30mL portions of diethyl ether. The aqueous layer was acidified with 1N aqueous sulfuric acid solution and extracted with two 50mL dichloromethane. The dichloromethane layers were combined, washed with water, dried over sodium sulfate, filtered and concentrated in vacuum to give 1.3 g of 3-fluoro-2-nitrophenol as an orange oil (61% yield). Next, 3-fluoro-2-nitrophenol (1.13 g, 7.2 mmol) and pyridine (0.65 mL, 8 mmol) were dissolved in 15 mL of anhydrous dichloromethane and cooled in an ice bath. A solution of trifluoromethanesulfonic anhydride (1.33 mL, 7.9 mmol) dissolved in 3 mL of anhydrous dichloromethane was added slowly. After 4 hours of reaction, the reaction mixture was diluted with 100 mL of dichloromethane and washed sequentially with two 30 mL aqueous saturated sodium bicarbonate solutions, two 30 mL aqueous 1N sulfuric acid solutions, and two 30 mL of water. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuum to give 2 g of the target product as a light brown oil (96% yield).

References

[1] Patent: WO2005/30213, 2005, A1. Location in patent: Page/Page column 182-183
[2] Magnetic Resonance in Chemistry, 1996, vol. 34, # 6, p. 440 - 446
[3] Journal of Labelled Compounds and Radiopharmaceuticals, 2006, vol. 49, # 7, p. 623 - 634
[4] Patent: WO2011/106986, 2011, A1
[5] ChemMedChem, 2017, vol. 12, # 17, p. 1436 - 1448