6-Bromo-2-methylpyridine-3-carboxaldehyde Chemical Properties

Boiling point:

285℃

Density 

1.577

Flash point:

126℃

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

pka

-0.29±0.10(Predicted)

Appearance

Light yellow to brown Solid

InChI

InChI=1S/C7H6BrNO/c1-5-6(4-10)2-3-7(8)9-5/h2-4H,1H3

InChIKey

CUTAVXXGKKXAHQ-UHFFFAOYSA-N

SMILES

C1(C)=NC(Br)=CC=C1C=O

6-Bromo-2-methylpyridine-3-carboxaldehyde Usage And Synthesis

Synthesis

General procedure for the synthesis of 6-bromo-2-methylnicotinic aldehyde from 2,5-dibromo-6-methylpyridine and N,N-dimethylformamide: To a solution of 3,6-dibromo-2-methylpyridine (60 g, 239 mmol) in tetrahydrofuran (THF, 600 mL) under nitrogen protection was slowly added at -78°C n-butyllithium (n-BuLi, 100 mL. 251 mmol). The reaction mixture was stirred continuously at -78 °C for 1 hour. Subsequently, N,N-dimethylformamide (DMF, 20.4 mL, 263 mmol) was added dropwise and stirring was continued at -78 °C for 1 hour. The reaction mixture was slowly warmed to 25 °C and the reaction was quenched by the addition of 1 M aqueous hydrochloric acid (300 mL). This reaction mixture was combined and processed with five other parallel reactions (30 g, 120 mmol and 4 x 50 g, 199 mmol of 3,6-dibromo-2-methylpyridine, respectively, maintaining the same reagent and solvent ratios). The combined reaction mixtures were extracted with ethyl acetate (EtOAc, 800 mL × 4), and the combined organic layers were washed with deionized water (H2O, 300 mL × 3), dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to afford the target product, 6-bromo-2-methylnicotinic aldehyde (260 g, 492 mmol, 42.5% combined yield), as a red oil The product was analyzed by NMR hydrogen spectroscopy. The product was confirmed by nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 400 MHz, chloroform-d): δ10.28 (s, 1H), 7.92 (d, J=7.9 Hz, 1H), 7.64 (s, 1H), 2.88-2.83 (m, 3H). Liquid chromatography-mass spectrometry (LCMS) analysis showed [M+H]+ peaks at m/z = 200.1 and 202.1.

References

[1] Patent: WO2007/22371, 2007, A2. Location in patent: Page/Page column 51
[2] Patent: CN106608879, 2017, A. Location in patent: Paragraph 0310-0313
[3] Patent: WO2017/145050, 2017, A1. Location in patent: Page/Page column 25-26