2,6-Bis(bromomethyl)pyridine

Uses

2,6-Bis(bromomethyl)pyridine may be used in the preparation of the following:

• a new pyridine-pyrazole derivative, 2,6-bis(3,5-diphenylpyrazol-1-ylmethyl)pyridine
• a large macrocyclic ligand, N(1),N(7)-pyridine-2,6-dimethyl-N(2),N(6)-bis(6-(3-(1H-benzo[d]imidazol-1-yl)propanamido)pyridin-2-yl)pyridine-2,6-dicarboxamide dibromide
• small-ring, potentially tridentate Se(2)N(pyridyl)-donor macrocycles

General Description

Crystal of 2,6-bis(bromomethyl)pyridine has the molecules related by a c-glide-plane operation. Molecules are arranged into stacks along the c axis. It participates in the synthesis of dicationic imidazolium-linked cyclophane.

Synthesis

1195-59-1

7703-74-4

Example 15 Synthesis of 2,6-bis(bromomethyl)pyridine. To pyridine-2,6-dimethanol (2 g, 14 mmol) was slowly added 60% hydrobromic acid (15 mL). The reaction mixture was heated to reflux at 125 °C for 6 h and subsequently cooled to room temperature. The reaction residue was dissolved in water (50 mL) to form a yellow solution. To this solution saturated sodium bicarbonate solution was added dropwise until the pH reached 8. The resulting aqueous solution was extracted with dichloromethane (4 x 50 mL) and the organic layers were combined and dried over anhydrous sodium sulfate. The solvent was removed by rotary evaporation and the resulting crude product was purified by fast column chromatography (ethyl acetate/hexane, 1:9 to 1:4 gradient elution) to afford 2,6-bis(bromomethyl)pyridine (3.5 g, 96% yield) as a white solid. The structure of the product was analyzed by 1H NMR (500 MHz, CDCl3) δ 4.53 (s, 4H), 7.36-7.38 (d, J = 8.0 Hz, 2H), 7.68-7.71 (dd, J = 7.5,8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 33.8,123.1,138.4, 157.0; LC-TOF (M + H+) calculated value C7H8Br2N 263.90235, measured value 263.90193 confirmed.

References

[1] Patent: US2010/203613, 2010, A1. Location in patent: Page/Page column 10
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 7, p. 2039 - 2048
[3] Organic and Biomolecular Chemistry, 2014, vol. 12, # 47, p. 9601 - 9620
[4] European Journal of Organic Chemistry, 1999, # 9, p. 2373 - 2381
[5] European Journal of Organic Chemistry, 2017, vol. 2017, # 35, p. 5252 - 5261