3-METHOXY-4-NITROBENZALDEHYDE

A dispersion of (3-methoxy-4-nitrophenyl)methanol (43) (1.4 mmol) and pyridinium dichromate (2.3 mmol) in dry DCM(38 mL) was stirred 17 hours at room temperature and a mixture of celite and silica was added. 3-Methoxy-4-nitrobenzyl alcohol (4.70g, 25.66mmol) was added to DCM (50mL), and MnOStep 1 : To a solution of 3-methoxy-4-nitrobenzyl alcohol (5g) in DCM ( 100 mL) was added PDC (1 .5 eq) and molecular sieves (6.0 g). The mixture was stirred at room temperature for 2h and diluted with EtTo a solution of 3-methoxy-4-nitrobenzyl alcohol (5g) in DCM (100 mL) was added PDC (1.5 eq) and molecular sieves (6.0 g). The mixture was stirred at room temperature for 2h and diluted with Et.20 (100 mL). The mixture was filtered through a Celite pad and solvent was evaporated. The residue was washed with a small amount MeOH to give off white solid (3.7 g, yield 74percent).To a solution of 3-hydroxy-4-nitrobenzaldehyde (2.000 g, 11.98 mmol) in DMF (24 ml) were added K2C03 (1.687 g, 12.22 mmol) and iodomethane (1.52 ml, 24.44 mmol). The reaction mixture was stilTed at room temperature for 4 hours. The mixture was diluted with water and extracted with EtOAc twice. The combined organics were washed with asaturated solution of NaHCO3 (3 times), with water, with saturated solution of NaC1, dried over MgSO4, filtered and evaporated to give intermediate ha (2.137 g, 98percent). ‘H NMR (500 MHz, CDC13) ö 10.06 (s, 1H), 7.93 (d, J= 8.1 Hz, 1H), 7.60 (s, 1H), 7.54 (dd, J= 8.1, 1.4 Hz, 1H), 4.04 (s, 3H).Example 39 : Synthesis of (1E, 6E)-1-(3-hydroxy-4-methoxyphenyl)-7-(3-methoxy-4-nitrophenyl)hepta-1, 6-diene-3, 5-dione (CU049); (1) Synthesis of 3-methoxy-4-nitrobenzaldehyde; 3-Hydroxy-4-nitrobenzaldehyde (500 mg, 2.99 mmol) and potassium carbonate (0.42 g, 3.0 mmol) were dissolved in 6.0 mL of N, N-dimethyformamide. After addition of iodemethane (0.38 mL, 6.0 mmol) at room temperature, the mixture was stirred for 5 h at the same temperature. The reaction mixture was diluted with ethyl acetate and water, and separated. The organic layer was washed with brine twice, and dried over MgSO3A. 3-Methoxy-4-nitro-benzaldehydeA mixture of 2-hydroxy-4-nitro-benzaldehyde (8.0 g, 47.9 mmol), methyl iodide (10.2 g, 71.9 mmol) and potassium carbonate (6.61 g, 47.9 mmol) in DMF (80 mL) was stirred at 60°C for 3 hours. The cooled reaction mixture was diluted with EtOAc (100 mL), washed with water (200 mL), dried (Na2SO4) and evaporated under reduced pressure to give the title compound (6.5 g, 75percent) which was used without further purification.(a) . 3-Methoxy-4-nitro-benzaldehyde A mixture of 3-hydroxy-4-nitrobenzaldehyde (51 .3 g), iodomethane (38.3 ml) and potassium carbonate (85 g) in DMF (250 ml) was stirred at 60 °C for 1 h. The reaction mixture was cooled to room temperature and poured into water. The solids were collected by filtration and dried in 10 vacuo (50 °C). Yield: 49.7 g.To 20 g (0.12 mol) of 3-hydroxy-4-nitrobenzaldehyde in 200 ml of anhydrous DMF are added 42 g (0.13 mol) of caesium carbonate. The solution obtained is ultrasonicated for 5 minutes, and 9.4 ml (0.29 mol) of methyl iodide are then added. The reaction medium is heated at 80°C for 18 hours and then diluted with ethyl acetate. The organic phase is washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated under reduced pressure. The residue is recrystallized from 300 ml of a hot 1/2 DMF/ethanol mixture. The crystals formed are filtered off, rinsed with cold ethanol and with hexane, and then dried under reduced pressure. 12.1 g of a solid are obtained.Methyl iodide (55.2 g, 389.2 mmol) was added dropwise to a stirred mixture of 3-hydroxy-4- nitrobenzaldehyde (50 g, 288.4 mmol) and potassium carbonate (53.8 g, 389.2 mmol) in DMF (250 ml). The reaction mixture was stirred overnight, poured into ice-cold water, and the precipitated solid was collected by filtration. The resulting solid was dried on a high vacuum overnight to obtain 53.4 g of 3-methoxy-4-nitrobenzaldehyde.1H NMR (CDCI3) 6: 10.06 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.60 (d, J = 0.8 Hz, 1H), 7.54 (dd, J = 8.2, 1.2 Hz, 1H), 4.02 (s, 3H).Nitric acid (0.46 mL, 11.0 mmol) and sulfuric acid (0.59 mL, 11.1 mmol) were slowly added to 3-methoxybenzaldehyde (1a) (0.5 g, 3.7 mmol) at -10 ° C and stirred for 1 hour do. Stir for an additional hour at room temperature. Add the ice water to the reaction mixture and sift the resulting precipitate in the filter paper and wash it with water. The filtered precipitate is dissolved in ethyl acetate, the water is removed using magnesium sulfate, and the filtrate is concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 10: 1) to obtain 1b compound in the form of yellow powder (49percent yield):

Molecular Weight:181.15
XLogP3:1.4
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:2
Exact Mass:181.03750770
Monoisotopic Mass:181.03750770
Topological Polar Surface Area:72.1
Heavy Atom Count:13
Complexity:201
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes