Uses
4-Methoxy-2-nitrobenzaldehyde is soluble in both water and ethanol. Its uses include the study of enzyme inhibition and regulation of gene expression. As an inhibitor of drug-metabolizing enzymes, it binds to the active site of the enzyme and impedes its catalytic function. In addition, it is an important tool for studying the regulation of gene expression.
Synthesis
Example 4 Preparation of 3-[7-(1-methylpiperidin-4-yloxy)quinazolin-2-yl]aminobenzenesulfonamide
Step 1. Preparation of 4-methoxy-2-nitrobenzaldehyde
4-Methyl-3-nitroanisole (20.43 g, 0.122 mol, 1.0 eq.) was dissolved in 480 mL of CCl4 under the protection of Ar atmosphere. N-bromosuccinimide (NBS, 48.94 g, 0.275 mol, 2.2 eq.) was added to the solution as a one-time addition, followed by benzoyl peroxide (0.67 g, 2.76 mmol). The reaction mixture was stirred under reflux conditions for 4.5 hours. An aliquot was analyzed by 1H NMR showing that about 90% of the starting material was converted to the dibromo derivative. The reaction mixture was cooled to room temperature and concentrated. The residual CCl4 was removed by azeotropic distillation with acetone twice. The residue was dissolved in acetone (1 L) and silver carbonate (Ag2CO3, 37.1 g, 0.135 mol, 1.1 equiv) and water (100 mL) were added. The reaction mixture was stirred at room temperature overnight. The reaction progress was monitored by TLC (unfolding agent ratio: EtOAc:hexane = 3:7) and the formation of new spots was observed. The reaction mixture was filtered through a PP028218.0002 filter, the filter cake was washed with acetone and the filtrate was concentrated. To the crude product, 340 mL of water was added and the product was extracted with EtOAc (800 mL, 400 mL). The emulsion formed was filtered through diatomaceous earth to separate the organic and aqueous layers. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated to give 8.27 g of crude product. The crude product was purified by column chromatography (eluent: EtOAc/hexane) to give 14.7 g (67% yield) of the pure compound 4-methoxy-2-nitrobenzaldehyde.
References
[1] Patent: WO2007/117607, 2007, A2. Location in patent: Page/Page column 309-310
[2] Journal of the Chemical Society, 1949, p. Spl. 231
[3] Chemical and Pharmaceutical Bulletin, 1962, vol. 10, p. 856 - 865
[4] J. Gen. Chem. USSR (Engl. Transl.), 1960, vol. 30, p. 3091 - 3095
[5] Zhurnal Obshchei Khimii, 1960, vol. 30, # 9, p. 3118
