4,5-Dimethoxy-2-nitrobenzyl bromide

Uses

1-(Bromomethyl)-4,5-dimethoxy-2-nitrobenzene is a useful research chemical.

Uses

4,5-Dimethoxy-2-nitrobenzyl bromide (DMNB bromide, 6-nitroveratryl bromide) is suitable reagent used in the synthesis of N-(4,5-dimethoxy-2-nitrobenzyl)vanillylamine which forms caged vanilloid. It may be used in the synthesis of the following:

• 4-(4′,5′-dimethoxy-2-nitrobenzyloxy)benzaldehyde, a DMNB-caged aldehyde
• N-[4-[(4,5-dimethoxy-2-nitrobenzyl)oxy]-3-methoxybenzyl]acetamide
• caged derivative of pyridostatin ([C]-PDS)
• photosensitive polyimide (PI-DMNB)
• caged β-ecdysone
• 4-tert-butyldimethylsilyloxy-1-(2-deoxy-3,5-di-O-toluoyl-β-D-ribofuranosyl)-2-(6-nitroveratrylthio)-1H-benzimidazole, an intermediate in synthesis of phosphoramidite bearing 4-hydroxy-2-mercaptobenzimidazole (SB^NV) nucleobase
• alkylation of dihydrofluorescein
• 4-(4′,5′-Dimethoxy-2′-nitrobenzyloxy)benzaldehyde

General Description

4,5-Dimethoxy-2-nitrobenzyl bromide (DMNBB, 1-(Bromomethyl)-4,5-dimethoxy-2-nitrobenzene) is a 4,5-dimethoxy-2-nitrobenzyl derivative. 4,5-Dimethoxy-2-nitrobenzyl (DMNB) group of DMNBB is used as a photolabile protecting group in caging technology to develop pro-drugs. Synthesis of 1-(bromomethyl)-4,5-dimethoxy-2-nitrobenzene by using 6-nitroveratraldehyde as starting reagent has been reported.

Synthesis

1016-58-6

53413-67-5

Step 1: A tetrahydrofuran (THF, 100 mL) solution of phosphorus tribromide (27.1 g, 100.0 mmol) was added slowly and dropwise through a dosing funnel to a stirring solution of 4,5-dimethoxy-2-nitrobenzenemethanol (10.7 g, 50.0 mmol) in THF (200 mL) under nitrogen protection. The reaction mixture was stirred overnight and the THF was removed by distillation under reduced pressure.The residue was partitioned with saturated aqueous sodium bicarbonate (NaHCO3) to separate the organic layer. The organic layer was subsequently washed with saturated aqueous NaHCO3 and dried with anhydrous magnesium sulfate (MgSO4). After filtration, the filtrate was concentrated to give a dark yellow oil. The oil was purified by silica gel column chromatography (SiO2, elution gradient: hexane/ethyl acetate from 4:1 to 3:1). Concentration of the product-containing eluate gave 11.8 g of 1-(bromomethyl)-4,5-dimethoxy-2-nitrobenzene as a bright yellow solid in 86% yield.

References

[1] Chemical Communications, 2017, vol. 53, # 68, p. 9470 - 9473
[2] Patent: WO2017/95704, 2017, A1. Location in patent: Page/Page column 58
[3] Journal of Organic Chemistry, 1990, vol. 55, # 5, p. 1585 - 1589
[4] Photochemical and Photobiological Sciences, 2012, vol. 11, # 3, p. 548 - 555
[5] European Journal of Medicinal Chemistry, 2012, vol. 55, p. 125 - 136