Preparation and application of 3-bromo-4-methyl-5-nitropyridine_Industrial additives

Preparation and application background and overview of 3-bromo-4-methyl-5-nitropyridine

3-Bromo-4-methyl-5-nitropyridine is an organic synthesis intermediate that can be prepared from 3-bromo-4-chloro-5-nitropyridine in two steps.

Preparation and application of 3-bromo-4-methyl-5-nitropyridine

Step 1: To a suspension of sodium hydride (2.02g, 60%, 50.5mmol) in DMF (30mL) was added diethyl malonate (7.71mL, 50.5mmol) in an ice bath. The mixture was stirred at 0 °C for 30 min, then a solution of 3-bromo-4-chloro-5-nitropyridine (6 g, 25.3 mmol) in DMF (20 mL) was added. The mixture was stirred at 0°C for 20 minutes and then at room temperature for a further 2 hours. The reaction was quenched with water (1000 mL), the mixture was extracted with DCM, and the organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to give a brown oil, which was used directly in the next step. LC-MS: [M+H]⁺=363.1, 364.0.

Step 2: Stir the mixture of the product of step 1 (8g, 13.29mmol) and hydrochloric acid (4M, 50mL, 200mmol) at room temperature for 20h. The mixture was basified to pH=10 by aqueous NaOH solution (10M) under ice bath. It was then extracted with DCM, the organic layer was dried over magnesium sulfate, filtered through boric acid and concentrated in vacuo, the residue was purified by CombiFlash, eluting with ethyl acetate in hexane (5-15%, 30 min), collecting the desired From the fraction, 3-bromo-4-methyl-5-nitropyridine (2.1 g, 73.4%) was obtained as a yellow solid. ¹HNMR (MHz, DMSO-cfe) δ9.06 (s, 1H), 9.02 (s, 1H), 2.56 (s, 3H).

Preparation and application of 3-bromo-4-methyl-5-nitropyridine

For the preparation of 3-bromo-5-nitro-4-pyridine benzaldehyde. The method was as follows: To a solution of 3-bromo-4-methyl-5-nitropyridine (2.1g, 9.68mmol) in DMF (10mL) was added DMF-DMA (2.59mL, 19.35mmol). The mixture was stirred at 90°C for 3 hours. The mixture was then cooled to room temperature and diluted with THF (25 mL). Then a solution of NalO₄ (methoxypyridine 6.13g, 28.7mmol) in water (25mL) was added. The mixture was stirred at room temperature for 20 hours. The mixture was then concentrated in vacuo. The mixture was diluted with water and extracted with DCM. The organic layer was dried over magnesium sulfate, filtered, and the filter was purified by CombiFlash, eluting with ethyl acetate in hexanes (5-20%, 30 min) and collecting the desired fractions to give 3-bromo-5-nitro- 4-Pyridinebenzaldehyde (1.6g, 72.5%), as a white solid. ¹HNMR (MHz, chloroform-cOδ10.27 (s, 1H), 9.30 (s, 1H), 9.11 (s, 1H).