2,3,5,6-Tetrafluoropyridine

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Cat Number

INT2875185

CAS Number

2875-18-5

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Product Detail Description Scientific Support Customer Q&A

CAS Number

2875-18-5

EINECS

622-979-9

Storage

Inert atmosphere, 2-8℃

Molecular Formula

C5HF4N

Molecular Weight

151.06

Smiles

C1(F)=NC(F)=C(F)C=C1F

Appearance

Colorless to Light yellow

Boiling Point

102℃

Relative Density

1.499

General Description

2,3,5,6-Tetrafluoropyridine is a polyfluorinated heterocyclic compound characterized by a pyridine ring where four of the five available carbon-bonded hydrogen atoms have been replaced by fluorine. This electron-deficient aromatic system is a highly versatile building block in the synthesis of specialized pharmaceuticals, agrochemicals, and advanced materials. Its unique chemical reactivity, driven by the strong inductive effect of the fluorine substituents, makes it an essential intermediate for introducing specific fluorinated motifs into complex molecular architectures.

Mechanism of Action

As a synthetic intermediate, 2,3,5,6-tetrafluoropyridine functions primarily as an electrophilic scaffold. The four fluorine atoms significantly lower the electron density of the pyridine ring, making the C4 position or the carbon-fluorine bonds highly susceptible to nucleophilic aromatic substitution reactions. This allows for the precise introduction of various functional groups, such as amines, alkoxides, or thiols, under relatively mild conditions.

Application

2,3,5,6-Tetrafluoropyridine is extensively utilized in the pharmaceutical industry for the development of fluorinated antiviral agents, kinase inhibitors, and anti-inflammatory drugs. In the agrochemical sector, it serves as a precursor for high-potency herbicides and fungicides that require enhanced environmental stability and systemic activity. It also acts as a valuable reagent in organic synthesis for the preparation of pentafluoropyridine derivatives and other highly functionalized heterocyclic compounds.

The reactivity of 2,3,5,6-tetrafluoropyridine derivatives bearing various substituents at the 4-position was systematically investigated. These electron-deficient heteroaromatic systems were evaluated for their propensity to undergo sequential nucleophilic aromatic substitution and subsequent annelation to form tetrahydropyrido[2,3-b]pyrazine scaffolds. When the 4-position was occupied by hydrogen or an electron-withdrawing group such as bromine, cyano, or nitro, reaction with N,N′-dimethylethylenediamine proceeded smoothly to afford the corresponding fused bicyclic systems. In contrast, the presence of electron-donating groups such as methoxy, ethoxy, diethylamino, or isopropylamino at the 4-position significantly impeded annelation, rendering the formation of ring-fused products considerably more challenging.

Fig. 1 Synthesis of tetrahydropyrido[2,3-b]pyrazine scaffolds from pentafluoropyridine. (Hargreaves C A.; et al. 2007)

References

Hargreaves C A, et al. Synthesis of tetrahydropyrido [2, 3-b] pyrazine scaffolds from 2, 3, 5, 6-tetrafluoropyridine derivatives. Tetrahedron, 2007, 63(24): 5204-5211.

What is the primary chemical characteristic of 2,3,5,6-tetrafluoropyridine?

It is a highly electron-deficient heterocycle, which makes it an excellent substrate for nucleophilic aromatic substitution reactions.

How do the four fluorine atoms in 2,3,5,6-tetrafluoropyridine affect its reactivity?

They strongly withdraw electrons from the ring, significantly increasing its reactivity toward nucleophiles compared to unsubstituted pyridine.

What are the common industrial uses for 2,3,5,6-tetrafluoropyridine?

It is primarily used as a key intermediate in the synthesis of fluorinated pharmaceuticals and advanced agrochemical products.

Can 2,3,5,6-tetrafluoropyridine be used to create pentafluoropyridine?

Yes, it can be further fluorinated at the C4 position to synthesize pentafluoropyridine, another important chemical intermediate.