2-Fluoro-4-methylpyridine NEW

2-Fluoro-4-methylpyridine is an organic compound belonging to the class of heterocyclic aromatic compounds, specifically a fluorinated pyridine derivative. Here's a detailed breakdown of its chemical identity:

1. Core Structure: Pyridine Ring

• A 6-membered aromatic ring with 5 carbon atoms and 1 nitrogen atom (chemical formula: C₅H₅N).

• The nitrogen has a lone pair, making pyridine basic and electron-deficient (π-deficient).

2. Substituents:

• Fluorine (-F) at position 2:
  Directly attached to carbon #2 (adjacent to the nitrogen). Fluorine is highly electronegative, making this position electron-withdrawing and influencing reactivity.

• Methyl group (-CH₃) at position 4:
  Attached to carbon #4 (meta to nitrogen). Methyl groups are electron-donating and increase lipophilicity.

3. Chemical Formula:

• C₆H₆FN
  (6 carbons, 6 hydrogens, 1 fluorine, 1 nitrogen).

4. Molecular Weight:

• 111.12 g/mol

5. Key Properties:

• Physical State: Typically a colorless to pale-yellow liquid at room temperature.

• Boiling Point: ~140–145°C (varies slightly with purity).

• Solubility:

• Miscible with organic solvents (e.g., ethanol, acetone, DCM).

  Low solubility in water.

• Reactivity:

• The 2-fluoro group is highly reactive due to the adjacent nitrogen, making it susceptible to nucleophilic substitution (e.g., with amines, alkoxides).

  The 4-methyl group can undergo oxidation (to -COOH) or halogenation (e.g., bromination).

6. Synthesis:

Common routes include:

• Halogen exchange on 2-chloro-4-methylpyridine using KF or CsF.

• Direct fluorination of 4-methylpyridine via Balz-Schiemann or other methods.

• Cross-coupling reactions on pre-fluorinated pyridine intermediates.

7. Applications:

• Pharmaceutical Intermediates:
  Used to synthesize bioactive molecules (e.g., agrochemicals, drugs) due to fluorine's role in enhancing metabolic stability, lipophilicity, and binding affinity.

• Agrochemicals:
  Building block for herbicides, fungicides, or insecticides.

• Ligands in Catalysis:
  Fluoropyridines act as ligands for transition metals in catalysis.

• Material Science:
  Fluorinated heterocycles are used in liquid crystals, OLEDs, or polymers.

8. Safety & Handling:

• Hazardous: Flammable liquid, toxic if ingested/inhaled, and corrosive to skin/eyes.

• Precautions: Use in a fume hood with PPE (gloves, goggles). Avoid strong oxidizers.

• Storage: Keep in a cool, dry place under inert atmosphere (e.g., N₂).

9. CAS Number:

• 349-90-0 (Unique identifier for chemical databases).

Structural Diagram:

      F

      │

   1 ┌─┐ 6  

  N ─┤ ├─H  

   2 │ │ 5  

H─C ─┼─C─CH₃ (4-methyl)  

   3 │ │ 4  

H─C ─┴─C─H  

Numbering follows pyridine convention (N = position 1).

Why is it Significant?

Fluorine substitution at the 2-position (ortho to N) dramatically alters electronic properties and reactivity compared to non-fluorinated pyridines. This makes it a valuable synthon for designing complex molecules in medicinal chemistry and materials science. The 4-methyl group adds steric and electronic flexibility for further functionalization.