2-FLUORO-3-METHOXYBENZOIC ACID

2-FLUORO-3-METHOXYBENZOIC ACID Property

Melting point:

157-160°C

Boiling point:

296.6±20.0 °C(Predicted)

Density 

1.307±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

form 

powder to crystal

pka

3.15±0.10(Predicted)

color 

White to Light yellow

InChI

InChI=1S/C8H7FO3/c1-12-6-4-2-3-5(7(6)9)8(10)11/h2-4H,1H3,(H,10,11)

InChIKey

AVGWCJLTQZQLCN-UHFFFAOYSA-N

SMILES

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

Safety

Hazard Codes 

Xi,Xn

Risk Statements 

36/37/38-22

Safety Statements 

26-36/37/39

HazardClass 

IRRITANT

HS Code 

2918999090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

P271Use only outdoors or in a well-ventilated area.

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

P302+P352IF ON SKIN: wash with plenty of soap and water.

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.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

2-FLUORO-3-METHOXYBENZOIC ACID Chemical Properties,Usage,Production

Uses

2-Fluoro-3-methoxybenzoic acid (2FMBA) is an intramolecular lithium compound that has been shown to be a potent inhibitor of dihydrofolate reductase. Experiments have shown that 2FMBA can inhibit bacterial growth, bind to DNA, and inhibit RNA synthesis in bacteria.

Synthesis

Step 1. Preparation of 2-fluoro-3-methoxybenzoic acid. Potassium tert-butoxide (30.80 g, 274 mmol) was dissolved in anhydrous tetrahydrofuran (300 mL) under nitrogen protection and the mixture was cooled to -78 °C. A hexane solution of 1.6 M n-butyllithium (172 mL, 275 mmol) was slowly added dropwise, and stirring was continued for 15 minutes after completion of the drop. Subsequently, 2-fluoroanisole (31.35 g, 248 mmol) was added and the reaction mixture continued to be stirred at -78 °C for 1.8 hours. Upon completion of the reaction, the mixture was slowly poured into a 2 L Erlenmeyer flask containing dry ice and gradually warmed to room temperature. Water (250 mL) was added to dilute and the organic layer was separated by extraction with ether (160 mL). The aqueous layer was acidified with concentrated hydrochloric acid to pH < 2. A solid was precipitated and collected by filtration to give 2-fluoro-3-methoxybenzoic acid (21.43 g, 51% yield) as a yellow solid. Melting point 155-160 °C. 1H NMR (acetone-d6, 300 MHz) δ 7.46 (ddd, J = 6.0, 1.8, 1.4 Hz, 1H), 7.36 (dt, J = 1.6, 8.1 Hz, 1H), 7.20 (dt, J = 1.4, 8.1 Hz, 1H), 3.92 (s, 3H); 19F NMR (acetone- d6, 300 MHz) δ -134.04 (m). Mass spectrum (ESI+): m/z 171 [M+H]+.

References

[1] Patent: US5547975, 1996, A