2,6-Difluoropyridine-3-boronic acid Chemical Properties

Melting point:

168 °C(Solv: ethyl acetate (141-78-6); ethyl ether (60-29-7))

Boiling point:

314.8±52.0 °C(Predicted)

Density 

1.44±0.1 g/cm3(Predicted)

storage temp. 

Inert atmosphere,2-8°C

Water Solubility 

Soluble in water

form 

powder to crystal

pka

6.77±0.58(Predicted)

color 

White to Light yellow

InChIKey

LCCZTROJRJFXNV-UHFFFAOYSA-N

CAS DataBase Reference

136466-94-9(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-37

HS Code 

29333990

2,6-Difluoropyridine-3-boronic acid Usage And Synthesis

Chemical Properties

2,6-difluoropyridine-3-boronic acid is a fluorine-containing substituted pyridine boronic acid derivatives, due to the fluorine atom and the atomic radius of the hydrogen atom is quite close, so when the hydrogen atom in the molecule is replaced by the fluorine atom, it will not cause the molecule to change the stereo configuration of the significant changes. However, due to the fluorine atom has a strong ability to absorb electrons, often make the original molecule of the electronic properties of the great changes, so that the fluorine-containing pyridine boronic acid has a good stability and a large dielectric anisotropy, so in recent years, the fluorine-containing pyridine boronic acid in medicine, especially the synthesis of new anticancer drugs and the material science has a very important role.

Uses

2,6-Difluoropyridine-3-boronic acid is a pyridine analogue containing a fluorine atom reactive group and boronic acid in its structure. It can be used as a reagent for fluorination or substitution reactions and as a synthetic intermediate for the preparation of other organic compounds.

Synthesis

The general procedure for the synthesis of 2,6-difluoropyridine-3-boronic acid from 2,6-difluoropyridine and trimethyl borate was carried out as follows: the synthesis was carried out according to the methodology reported in the literature [S1, S2] with appropriate modifications. First, a solution of lithium diisopropylammonium (LDA) was prepared by slow dropwise addition of a THF (20 mL) solution of diisopropylamine (3.4 mL) to n-butyllithium (1.67 M in n-hexane, 24 mmol, 14 mL) at 20 °C, followed by stirring at 0 °C for 20 min. Next, in another reaction flask, a solution of 2,6-difluoropyridine (20 mmol, 1.8 mL) in THF (20 mL) was stirred at -78 °C and the LDA solution prepared above was added via cannula. After continued stirring at -78 °C for 30 min, a solution of trimethyl borate (24 mmol, 2.5 g, 2.7 mL) in THF (10 mL) was added to the reaction mixture, followed by a slow warming up to room temperature over a period of 1 hour. Upon completion of the reaction, the reaction was quenched with 2 M aqueous sodium hydroxide solution (40 mL). The aqueous layer was separated and the pH was adjusted to 8 with 4 M hydrochloric acid followed by extraction with ethyl acetate (organic layer A). The pH of the aqueous layer was further adjusted to 6.5 with 4M hydrochloric acid, at which time insoluble organic matter was precipitated, and the extraction was repeated three times with ethyl acetate to give organic layer B. The pH of the aqueous layer was again adjusted to 4 with 4M hydrochloric acid, and the extraction was repeated three times with ethyl acetate to give organic layer C. Organic layers B and C were combined, dried with anhydrous sodium sulfate, and concentrated under reduced pressure to afford the crude product of 2,6-difluoropyridinium-3-boronate in 94% (3.0 g) yield. 94% (3.0 g, 19 mmol). The product could be used directly in the subsequent reaction without further purification.

References

[1] Journal of Fluorine Chemistry, 2016, vol. 181, p. 56 - 60
[2] Inorganic Chemistry, 2009, vol. 48, # 3, p. 1030 - 1037
[3] Patent: EP2727928, 2014, A1. Location in patent: Paragraph 0027
[4] Patent: US8859771, 2014, B2. Location in patent: Page/Page column 11
[5] Journal of Nanoscience and Nanotechnology, 2018, vol. 18, # 10, p. 7047 - 7052

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