2-bromo-5-nitrobenzaldehyde

General procedure: In an oven dried Schlenk tube, were added alcohol 1 (69.0–199.5 mg, 0.5 mmol), CuI (10 molpercent)and 1, 10-Phenanthroline (20 molpercent) and K3PO4 (2 mmol) followed by the addition of dioxane (2mL) at room temperature under open air atmosphere. The stirred reaction mixture was heated inan oil bath at 80 C for 7–48 h. Progress of the reaction was monitored by TLC till the reaction iscompleted. Then, the reaction mixture was cooled to room temperature, quenched with aqueousNH4Cl solution and then extracted with CH2Cl2 (3 10 mL). The organic layer was washed withsaturated NaCl solution, dried (Na2SO4), and filtered. Evaporation of the solvent under reducedpressure and purification of the crude material by silica gel column chromatography (petroleumether/ethyl acetate) furnished the aldehyde/ketone 2 (61–97percent).To a solution of 2-bromobenzaldehyde (10.0 g, 53.7 mmol) in HTo a solution of 2-bromobenzaldehyde (10.0 g, 53.7 mmol) in HKNO3 (1.09 g, 10.8 mmol) was added slowly to a stirred red solution of 2-bromobenzaldehyde (2.0 g, 10.8 mmol) in H2SO4 (10 mL) at 0 °C. After 30 minutes extra portion of KNO3 (0.16 g, 1.6 mmol) was added, and the reaction mixture was stirred for 2.5 hours at 0 °C. Then the reaction mixture was poured over ice water (50 mL), extracted with Et2O (3×25 mL). Combined organic layers were washed with water (30 mL), brine (40 mL) and dried over Na2SO4. Solvents were evaporated in vacuo. The residual yellow solid was recrystallized from EtOAc/hexane (1/2, 40 mL) to give pure nitroaldehyde SI-1e (1.32 g, 5.7 mmol, 53percent). Further recrystallization of evaporated mother liquor from EtOAc/hexane (1/3, 15 mL) gives additional nitroaldehyde SI-1e (0.75 g, 3.2 mmol, 30percent) of the same purity.A mixture of concentrated sulfuric acid (17.01 mL) andfuming nitric acid (2.250 mL) was cooled to 5 °C followedby the dropwise addition of 2—bromobenzaldehyde (3.15 mL, 27.0 mmol) over a period of 30 minutes. The mixture wasthen allowed to warm to room temperature and stirred for60 minutes. The reaction mixture was poured intoice/water (200 mL) and the precipitated solid isolated by filtration, washed with water and sucked dry to give a pale yellow solid. This was recrystallised from 50:50 cyclohexane:ethyl acetate (30 mL) to give the title compound as an off—white solid (3.39 g, 55percent) . ‘H NMR(300 MHz, CDC13) : 3 10.39 (s, 1H) , 8.72 (d, 1H) , 8.29 (dd, 1H) , 7.89 (d, 1H)Intermediate 17: l-(2-bromo-5-nitrophenyl)-N-methylmethanamine; Intermediate 17A:; [00237] Potassium nitrate (2.59 mL, 54.0 mmol) was added portionwise to a stirred and chilled (ice bath) solution of 2-bromobenzaldehyde (10 g, 54.0 mmol) in sulfuric acid (50 mL, 938 mmol) over 1 h. After 40 min an additional portion of KNO3 (0.72 g) was added. After 3 h stirring at 0 To a solution of 2-bromobenzaldehyde (10.0 g, 53.7 mmol) in H2SO4 (100 mL) was added K O3 (5.43 g, 53.7 mmol) in portions over 1 h at 0C. The mixture was stirred for 40 min and additional K O3 (0.72 g) was added. The reaction mixture was stirred at 0C for 3 h then poured into ice water. The resulting precipitate was collected by filtration, rinsed with water and recrystallized from EtOAc/Pentane to give 2-bromo-5-nitrobenzaldehyde (11.7 g, 94% yield) as a white solid. MS (ESI) calcd for C7H4BrN03: 228.9To a solution of 2-bromobenzaldehyde (10.0 g, 53.7 mmol) in H2SO4 (100 mL) was added KNO3 (5.43 g, 53.7 mmol) in portions over 1 h at 0 C. The mixture was stirred for 40 min and additional KNO3 (0.72 g) was added. The reaction mixture was stirred at 0 C. for 3 h then poured into ice water. The resulting precipitate was collected by filtration, rinsed with water and recrystallized from EtOAc/Pentane to give 2-bromo-5-nitrobenzaldehyde (11.7 g, 94% yield) as a white solid. MS (ESI) calcd for C7H4BrNO3: 228.9.KNO3 (1.09 g, 10.8 mmol) was added slowly to a stirred red solution of 2-bromobenzaldehyde (2.0 g, 10.8 mmol) in H2SO4 (10 mL) at 0 C. After 30 minutes extra portion of KNO3 (0.16 g, 1.6 mmol) was added, and the reaction mixture was stirred for 2.5 hours at 0 C. Then the reaction mixture was poured over ice water (50 mL), extracted with Et2O (3×25 mL). Combined organic layers were washed with water (30 mL), brine (40 mL) and dried over Na2SO4. Solvents were evaporated in vacuo. The residual yellow solid was recrystallized from EtOAc/hexane (1/2, 40 mL) to give pure nitroaldehyde SI-1e (1.32 g, 5.7 mmol, 53%). Further recrystallization of evaporated mother liquor from EtOAc/hexane (1/3, 15 mL) gives additional nitroaldehyde SI-1e (0.75 g, 3.2 mmol, 30%) of the same purity.A mixture of concentrated sulfuric acid (17.01 mL) andfuming nitric acid (2.250 mL) was cooled to 5 C followedby the dropwise addition of 2-bromobenzaldehyde (3.15 mL, 27.0 mmol) over a period of 30 minutes. The mixture wasthen allowed to warm to room temperature and stirred for60 minutes. The reaction mixture was poured intoice/water (200 mL) and the precipitated solid isolated by filtration, washed with water and sucked dry to give a pale yellow solid. This was recrystallised from 50:50 cyclohexane:ethyl acetate (30 mL) to give the title compound as an off-white solid (3.39 g, 55%) . 'H NMR(300 MHz, CDC13) : 3 10.39 (s, 1H) , 8.72 (d, 1H) , 8.29 (dd, 1H) , 7.89 (d, 1H)Intermediate 17: l-(2-bromo-5-nitrophenyl)-N-methylmethanamine; Intermediate 17A:; [00237] Potassium nitrate (2.59 mL, 54.0 mmol) was added portionwise to a stirred and chilled (ice bath) solution of 2-bromobenzaldehyde (10 g, 54.0 mmol) in sulfuric acid (50 mL, 938 mmol) over 1 h. After 40 min an additional portion of KNO3 (0.72 g) was added. After 3 h stirring at 0 0C, the mixture was poured over ice water, and the product was filtered and washed with water. The crude pale yellow solid was recrystallized from 1 : 1 ethyl acetate/hexane (-60 mL) to give Intermediate 17A (6.789 g, 29.5 mmol, 54.6 % yield). MS (ESI) m/z 230, 232 (M+H)+.a 2--Bromo-5-nitrobenzaldehyde A nitrating acid prepared at -10 C. by adding 55 ml of concentrated H2 SO4 to 20 ml of 98 percent HNO3 was added dropwise, in the course of 60 minutes, to a solution of 63.4 g (0.34 mole) of 2-bromobenzaldehyde in 110 ml of concentrated H2 SO4 at -5 C. Stirring was continued for a further 45 minutes, after which the reaction mixture was poured onto 550 g of ice, and the precipitated solid was filtered off under suction, washed with water, then with 10 percent strength Na2 CO3 solution and again with water. Drying under reduced pressure at 50 C. gave 72 g (92% of theory) of product as a yellow solid of melting point 86-88 C.General procedure: 2-bromobenzaldehyde (1 mmol), 2-formylphenylboronic acid (1.2 mmol), Pd(PPh3)2Cl2 (10 mol%) and K3PO4 (1.5 mmol) was taken in a two neck round bottomed flask. 5 mL DMSO was added to it and the reaction mixture was degassed properly with N2. Next the reaction was allowed to stir at 90 oC for 6 h. After the completion of the reaction, the reaction mixture was cooled to room temperature and to it were added CuCl (5 mol %) and TBHP (3 equivalent). It was stirred for another 1 h at rt. Then it was diluted with water and extracted with ethyl acetate several times. The organic parts were collected together and concentrated under vacuum after drying over Na2SO4. Products were purified by column chromatography using 60-120 mesh silica gel and 5:1 pet ether : ethyl acetate as the eluent.

Molecular Weight:230.02
XLogP3:1.9
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:228.93746
Monoisotopic Mass:228.93746
Topological Polar Surface Area:62.9
Heavy Atom Count:12
Complexity:192
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes