2-FLUORO-6-METHOXYPHENOL

2-FLUORO-6-METHOXYPHENOL Property

Boiling point:

130-131 °C36 mm Hg(lit.)

Density 

1.23 g/mL at 25 °C(lit.)

refractive index 

n20/D 1.52(lit.)

Flash point:

218 °F

storage temp. 

Inert atmosphere,Room Temperature

pka

8.71±0.10(Predicted)

form 

Liquid

color 

Clear colorless to light brown

Specific Gravity

1.230

InChI

InChI=1S/C7H7FO2/c1-10-6-4-2-3-5(8)7(6)9/h2-4,9H,1H3

InChIKey

YZNHPLVFLRSVHY-UHFFFAOYSA-N

SMILES

C1(O)=C(OC)C=CC=C1F

CAS DataBase Reference

73943-41-6(CAS DataBase Reference)

Safety

Hazard Codes 

Xi,C

Risk Statements 

36/37/38

Safety Statements 

26-37/39

WGK Germany 

3

HazardClass 

IRRITANT

HS Code 

29095000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H318Causes serious eye damage

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P280Wear protective gloves/protective clothing/eye protection/face protection.

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

P337+P313IF eye irritation persists: Get medical advice/attention.

2-FLUORO-6-METHOXYPHENOL Chemical Properties,Usage,Production

Chemical Properties

Clear colorless to light brown liquid

Synthesis

The general procedure for the synthesis of 2-fluoro-6-methoxyphenol from m-fluoroanisole was as follows: 4.0 mL (9.4 mmol) of 2.36 M n-butyllithium solution was slowly added dropwise over a period of 1 h to 10.0 mL of anhydrous tetrahydrofuran (THF) solution containing 1.28 g (10 mmol) of m-fluoroanisole (1) according to the method of Ladd and Weinstock The reaction temperature was maintained below -65 °C and cooled using a dry ice/acetone bath. The reaction mixture was stirred at -78 °C and under nitrogen protection for 2 hours. Subsequently, 1.17 g (11 mmol) of trimethoxyborane dissolved in 2.00 mL of anhydrous THF was added dropwise over 1 h at -78 °C and stirring was continued at -78 °C for 30 min. The reaction mixture was slowly warmed to 0 °C and 0.88 mL (15 mmol) of glacial acetic acid was added, followed by the dropwise addition of 1 mL (10 mmol) of 30% hydrogen peroxide (H2O2) solution. The reaction mixture was stirred at 25 °C overnight. After completion of the reaction, the reaction solution was diluted with 10 mL of water and extracted with THF (2 × 10 mL). The organic phases were combined and washed sequentially with H2O (2 × 7 mL) and 10% brine (2 × 3 mL). The organic phase was dried with anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure to give 1.16 g (80% yield) of 2-fluoro-6-methoxyphenol. The yields of successive replicate experiments were as follows: 15.5 g of product (63% yield) was obtained from 174 mmol of feedstock; 29.7 g of product (80% yield) was obtained from 261 mmol of feedstock. The structures of the products were analyzed by 1H NMR (300 MHz, CDCl3) δ 6.82-6.63 (m, 1H), 5.51 (s, 1H), 3.90 (s, 1H); 19F NMR (282 MHz, CDCl3) δ -137.61 ppm (m, 1F); EI-MS: m/z 142 (M+), 127.

References

[1] Synlett, 2014, vol. 25, # 20, p. 2891 - 2894
[2] Patent: WO2017/176812, 2017, A1. Location in patent: Paragraph 0405
[3] Journal of Medicinal Chemistry, 1990, vol. 33, # 8, p. 2204 - 2211
[4] Journal of Organic Chemistry, 1981, vol. 46, # 1, p. 203 - 206
[5] Journal of Chemical Research, Miniprint, 1986, # 1, p. 171 - 193