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TCI Practical Example: Direct Synthesis of Lithium Pyridine Sulfinate Using TIMSO

We are proud to present the synthesis of lithium 6-methoxypyridine-3-sulfinate using TIMSO and 5-bromo-2-methoxypyridine.

Used Chemicals

• 5-Bromo-2-methoxypyridine [B2398]
• Sulfur Dioxide 1-Methylpyrrolidine Adduct (= TIMSO) [U0113]
• Butyllithium (ca. 15% in Hexane, ca. 1.6mol/L)
• THF

Procedure

5-Bromo-2-methoxypyridine (1.00 g, 5.32 mmol) in THF (30 mL) was stirred at -78 °C for 5 minutes and butyllithium (ca. 1.6mol/L in hexane, 3.66 mL, 5.85 mmol) was added to the solution and stirred further for 40 minutes at same temperature. Then, TIMSO (1.06 g, 6.38 mmol) was added and stirred at room temperature for 30 minutes. The precipitated solid was collected by filtration and washed with acetone (2 x 20 mL) and diethyl ether (2 x 20 mL) to give 1 as a white solid (895 mg, 94% yield).

Experimenter’s Comments

The reaction mixture was monitored by NMR.

Analytical Data

Lithium 6-Methoxypyridine-3-sulfinate (1)

¹H NMR (270 MHz, D₂O); δ 8.09 (d, J = 1.9 Hz, 1H), 7.77 (dd, J = 6.2, 2.2 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 3.77 (s, 3H).

Lead Reference

• Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides
  • T. Markovic, B. N. Rocke, D. C. Blakemore, V. Mascitti, M. C. Willis, Chem. Sci. 2017, 8, 4437.

Other References

• Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions
  • T. Markovic, B. N. Rocke, D. C. Blakemore, V. Mascitti, M. C. Willis, Org. Lett. 2017, 19, 6033.