Preparation and application of 2,6-dibromonitrobenzene_Kain Industrial Additive

Background and overview^[1]

2,6-Dibromonitrobenzene can be used as a pharmaceutical synthesis intermediate. 2,6-dibromoaniline can be used as the reaction raw material and reacted with m-chloroperoxybenzoic acid to generate 2,6-dibromo-2- Nitrosobenzene is further oxidized to form 2,6-dibromonitrobenzene. 2,6-Dibromonitrobenzene can be used to prepare the intermediate (R)-1-(3-bromo-2-nitrophenyl)piperidin-3-ylcarbamic acid tert-butyl ester.

Apply^[1]

2,6-Dibromonitrobenzene can be used to prepare (R)-1-(2-amino-3-bromophenyl)piperidin-3-ylcarbamic acid tert-butyl ester: 2,6-dibromonitrobenzene Bromonitrobenzene 8.4g (30.0mmol), (R)-piperidin-3-ylcarbamic acid tert-butyl ester 3.2g (16mmol) were dissolved in DMA (20mL), DIEA 4.3mL (26mmol) was added, and the reaction mixture was React at 150°C for 10 hours, pour into water, extract with ethyl acetate, dry and spin off the solvent to obtain an oily substance, which is purified by column chromatography to obtain 5.58g of product, yield: 87.3%. Add 0.2g (0.5mmol) of (R)-1-(3-bromo-2-nitrophenyl)piperidin-3-ylcarbamic acid tert-butyl ester and 0.065g (1mmol) of zinc powder to methanol (3mL) , add hydrazine hydrate and 85% formic acid solution (2mL, v/v=1), stir for 5 hours under nitrogen protection at room temperature, filter, concentrate the organic layer, and dissolve the solid in dichloromethane and saturated NaCl solution , dried and concentrated to obtain 0.19g of crude product.

Preparation^[1]

Preparation of (1) 2,6-dibromo-2-nitrosobenzene

Add 9.8g (39mmol) of 2,6-dibromoaniline and 30g (139mmol) of 80% m-chloroperbenzoic acid into 500mL of methylene chloride and react at room temperature for 3 hours to obtain 7.24g of product. Rate: 70.0%.

Preparation of (2) 2,6-dibromonitrobenzene

Dissolve 1.23g (4.64mmol) of 2,6-dibromo-2-nitrosobenzene in glacial acetic acid (25mL) and H₂O_{2 (25mL), add HNO3 (0.83mL), raise the temperature to 90°C, react for 2 hours, add 50mL water, filter, and obtain 0.67g of the product 2,6-dibromonitrobenzene. Yield: 51.4%.}

References

[1]CN201110036979.4 Benzocyclic derivatives