Preparation background and overview of 2-bromo-5-cyanopyridine
2-Bromo-5-cyanopyridine, also known as 6-bromonicotinonitrile.
Preparation of 2-bromo-5-cyanopyridine
Synthesis of 6-bromonicotinonitrile.
Method 1:
Heat 6-chloronicotinonitrile (13.8 g, 100 mmol) in phosphorus tribromide (150 mL) at 145°C for 32 hours. After cooling, the mixture was concentrated in vacuo. Phosphorus tribromide (150 mL) was added to the residue and the mixture was heated at 145°C for a further 32 hours. After cooling, the mixture was concentrated in vacuo and a mixture of ice and water (500 mL) was added. Sodium bicarbonate was added to neutralize the mixture and the product was extracted with ethyl acetate (3×250 mL). The organic extracts were combined, washed with brine and dried over magnesium sulfate. The solvent was removed in vacuo and the residue was chromatographed (hexane-ethyl acetate) to obtain 14.9g (81%) 6-bromonicotinonitrile as a white solid: 1HNMR (MHz, CDCl 3)δ7.66(d,J=11.0Hz, 1H),7.80(dd,J=3.1,11.0Hz,1H),8.67 (d,J=3.1Hz,1H); MS (M+H)+ m/z=183.0,185.0.
Method 2:
Liskey et al. reported that 2-bromopyridine-5-boronic acid was dissolved in methanol and water, and then mixed with Cu(NO3)2, Zn(CN) 2 mica, react with CsF by heating and stirring at 80°C for 2 hours to prepare 2-bromo-5-cyanopyridine, the yield can reach 61%.
