4-Difluoromethoxy-3-hydroxybenzaldehyde Chemical Properties

Melting point:

85-90°C

Boiling point:

280.6±35.0 °C(Predicted)

Density 

1.395±0.06 g/cm3(Predicted)

storage temp. 

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

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

pka

7.85±0.35(Predicted)

color 

White

InChI

InChI=1S/C8H6F2O3/c9-8(10)13-7-2-1-5(4-11)3-6(7)12/h1-4,8,12H

InChIKey

ZLIKNROJGXXNJG-UHFFFAOYSA-N

SMILES

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

CAS DataBase Reference

151103-08-1(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi,Xn

Risk Statements 

36/37/38-51-22

Safety Statements 

26-36/37/39

WGK Germany 

3

Hazard Note 

Irritant

HS Code 

2913000090

4-Difluoromethoxy-3-hydroxybenzaldehyde Usage And Synthesis

Description

4-Difluoromethoxy-3-hydroxybenzaldehyde is an organofluorine compound, mainly used as an intermediate in organic synthesis. It is used in the synthesis of the impurity N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-3-hydroxybenzamide isolated from roflumilast crude^[1].

Chemical Properties

4-Difluoromethoxy-3-hydroxybenzaldehyde is white powder

Uses

4-Difluoromethoxy-3-hydroxybenzaldehyde is a phenyl alkyl ketone derivative used in the preparation of phosphodiesterase-4 (PDE4) inhibitors.

Synthesis

Example 10 Preparation of 4-difluoromethoxy-3-hydroxybenzaldehyde: 3,4-dihydroxybenzaldehyde (0.50 g, 3.62 mmol, Aldrich), methyl 2-chloro-2,2-difluoroacetate (0.52 g, 3.62 mmol, Aldrich), and potassium carbonate (0.50 g, 3.62 mmol) were placed in argon- protected DMF ( 5.0 mL). The reaction mixture was stirred at 60°C to 65°C for 3 hours. Upon completion of the reaction, the DMF was removed by distillation under reduced pressure. the residue was subjected to liquid-liquid partitioning with 3N HCl aqueous solution and ether. The aqueous phase was extracted three times with ether. The combined organic phases were washed sequentially with water and saturated saline, dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by fast column chromatography (silica gel, 25% ethyl acetate/hexane) to afford the title compound 4-difluoromethoxy-3-hydroxybenzaldehyde as a white solid (0.20 g, 38% yield). Melting point 83°C to 85°C.

References

[1] YAN LIN. Isolation, synthesis and structure confirmation of the impurity in crude roflumilast product[J]. Research on Chemical Intermediates, 2012. DOI:10.1007/s11164-012-0823-3.

4-Difluoromethoxy-3-hydroxybenzaldehyde(151103-08-1)Related Product Information

• Benzaldehyde
• 4-(Trifluoromethyl)benzaldehyde
• 4-Ethyl-5-fluoro-6-hydroxypyrimidine
• Protocatechualdehyde
• Veratraldehyde
• (Trifluoromethoxy)benzene
• p-Anisaldehyde
• 4-(Trifluoromethoxy)aniline
• 2,4-Dihydroxybenzaldehyde
• 2,4-Dimethoxybenzaldehyde
• 3,4-Difluorobenzaldehyde
• 4-Hydroxybenzaldehyde
• 3-Hydroxybenzaldehyde
• 2,4-Difluorobenzaldehyde
• CHLOROPHOSPHONAZO III
• Ezetimibe
• 2,2-Difluorobenzodioxole-5-carboxaldehyde
• 2,2-Difluorobenzodioxole-5-carboxylic acid