2-Hydroxy-3-trifluoromethylpyridine Chemical Properties

Melting point:

150-153°C

Boiling point:

223.7±40.0 °C(Predicted)

Density 

1.398±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

form 

powder to crystal

pka

9.67±0.10(Predicted)

color 

White to Almost white

InChI

InChI=1S/C6H4F3NO/c7-6(8,9)4-2-1-3-10-5(4)11/h1-3H,(H,10,11)

InChIKey

JHDCDEHVUADNKQ-UHFFFAOYSA-N

SMILES

C1(=O)NC=CC=C1C(F)(F)F

LogP

0.71 at 25℃

CAS DataBase Reference

22245-83-6(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi,Xn,T

Risk Statements 

36/37/38-65-20/21/22-20/21-36-25

Safety Statements 

26-36/37/39-36-45

RIDADR 

UN2811

HazardClass 

IRRITANT

HS Code 

29333990

2-Hydroxy-3-trifluoromethylpyridine Usage And Synthesis

Description

2-hydroxy-3-(trifluoromethyl)pyridine (or 3-(Trifluoromethyl)-2-pyridone) is a trifluoromethyl substituted 2-hydroxypyridine. It is used as a synthesis intermediate for ligands and bioactive ingredients in the application of drug discovery and catalytic reactions. In catalytic reactions, the amide group of 2-pyridone binds to transition metals, forming stable 5-/6-membered ring intermediates. Hence, 2-hydroxy-3-(trifluoromethyl)pyridine is widely used as a ligand in catalytic reactions such as directed C-H activation on meta-position. In addition, the trifluoromethyl substituent of 3-(trifluoromethyl)-2-pyridone tunes its metal-binding affinity and limits the reaction site for improving regioselectivity.

Chemical Properties

White powder

Uses

2-Hydroxy-3-trifluoromethylpyridine is a reactant in the synthesis of Pyrido[2,3-b]pyrazine, a TRPV1 antagonist .

Synthesis

General procedure: 2-hydroxypyridine (0.19 g, 2.0 mmol) and ferrocene (0.11 g, 0.6 mmol) were accurately weighed and placed in a dry two-necked flask and the atmosphere was replaced under argon protection. Dimethyl sulfoxide (8.0 mL), 3.0 mol/L trifluoromethyl iodine in dimethyl sulfoxide solution (2.0 mL) and 30% aqueous hydrogen peroxide solution (0.4 mL) were added sequentially to the flask, and the reaction mixture was stirred for 20 min at 40 °C to 50 °C. After completion of the reaction, the mixture was cooled to room temperature. The generation of 2-hydroxy-3-trifluoromethylpyridine was confirmed by 19F-NMR analysis using 2,2,2-trifluoroethanol as an internal standard (19F-NMR yield: 64%). Following the subsequent processing steps of Example 1, the target product 2-hydroxy-3-trifluoromethylpyridine was obtained as a white solid (0.081 g, yield: 50%). The structure of the product was determined by 1H-NMR (deuterated chloroform, δ 6.34 (dd, J = 6.9, 5.5 Hz, 1H), 7.65 (d, J = 5.6 Hz, 1H), 7.88 (d, J = 6.9 Hz, 1H), 13.25 (brs, 1H)), 13C-NMR (deuterated chloroform, δ 105.6, 120.4 (q, JCF = 31.4 Hz), 122.7 (q, JCF = 271.3 Hz), 139.2, 140.7 (q, JCF = 4.9 Hz), 161), 19F-NMR (deuterated chloroform, δ -66), and mass spectrometry (m/z: 163 [M]+) confirmed.

References

[1] Patent: EP2080744, 2009, A1. Location in patent: Page/Page column 7-8
[2] Journal of Fluorine Chemistry, 2010, vol. 131, # 1, p. 98 - 105

2-Hydroxy-3-trifluoromethylpyridine(22245-83-6)Related Product Information

• 2-Chloro-3-hydroxypyridine
• Azamethiphos
• CHLOROPHOSPHONAZO III
• 2-Chloro-3-(trifluoromethyl)pyridine
• 3-Hydroxypyridine
• 2,4,6-Collidine
• 2-(Trifluoromethyl)benzoic acid
• 3-(Trifluoromethyl)benzaldehyde
• 2-Hydroxypyridine
• 4-Methylpyridine
• 4-(Trifluoromethyl)pyridine
• 2-(Trifluoromethyl)pyridine
• 3-Trifluoromethylpyridine
• 2-Hydroxy-6-methyl-5-nitropyridine
• 2-Hydroxy-4-methoxybenzaldehyde
• 2-Hydroxy-4-methyl-5-nitropyridine
• 2-Hydroxy-4-methyl-3-nitropyridine
• 3-BROMO-6-HYDROXY-2-METHYLPYRIDINE