2-Methoxy-1-methyl-4-nitrobenzene

cream to yellow crystalline powder and chunks

General procedure: To a solution of 2-methyl-5-nitrophenol (613 mg, 4.0 mmol) in dehydrated DMF (7 mL) were added potassium carbonate (608 mg, 4.4 mmol) and iodoalkane (12.0 mmol) under an argon atmosphere. The mixture was heated at 40 °C for 2-3 h, then poured into water and extracted with EtOAc. The organic layer was washed with HTo a solution of 2-methyl-5-nitrophenol (309 mg, 2.02 mmol) and K2CO3 (400 mg, 2.90 mmol) in DMF (4.0 mL) was added MeI (855 mg, 6.02 mmol). The reaction mixture was stirred for 9 h at r.t. and then diluted with AcOEt. The organic layer was washed with water and brine, dried over MgSO4 and concentrated to give compound 13c as a dark yellow solid (251 mg, 1.50 mmol, 74percent), which was used for the next step without further purification. 1H-NMR (500 MHz, CDCl3) δ: 7.74 (1H, dd, J=2.0, 8.0 Hz), 7.64 (1H, d, J=2.0 Hz), 7.23 (1H, d, J=8.0 Hz), 3.90 (3H, s), 2.28 (3H, s).[0133] 2-Methoxy-4 nitrobenzyl N, N-bis(2-chloroethyl)phos-phordiamidate (15i). 2-methy-5-nitrophenol (1.53 g, 10 mmol), anhydrous potassium carbonate (1.03 g, 7.5 mmol), and iodomethane (1.56 g, 11 mmol) were suspended in 20 mL of dry acetone and heated to reflux for 5 hours. Water (10 mL) was added and acetone was evaporated. The residue was extracted with CH2Cl2 (220 mL). The CH2Cl2 phase was washed with saturated NaCl solution (220 mL) and dried over Na2SO4. After evaporation, the residue was purified by flash silica gel column chromatography (hexanes/EtOAc, 10:1) to afford 1-methyl-2-methoxy-4-nitrobenzene as a light yellow solid (1.2 g, 72percent). m.p. 72-73° C.; 1H NMR (CDCl3, 200 MHz) δ 2.32 (s, 3H), 3.94 (s, 2H), 7.29 (d, 1H, J=8.2 Hz), 7.68 (d, 1H, J=2.2 Hz), 7.79 (dd, 1H, J=2.2, 8.0 Hz). (500mg, 2.99mmol), NBS (586mg, 3.29mmol) and Benzoyl peroxide (72mg, 0.299mmol) were added into CCl4 (30mL) and stirred at 80C for 8h. The reaction mixture was evaporated. The residue was chromatographed (silicagel, Hexane/EtOAc=100:1) to give 1-(bromomethyl)-2-methoxy-4-nitrobenzene (DC-TEADin11-1, 662mg, 90%) as a white solid. 1H NMR (400MHz, Chloroform-d) delta 7.82 (dd, J=8.3, 2.2Hz, 1H), 7.73 (d, J=2.2Hz, 1H), 7.49 (d, J=8.3Hz, 1H), 4.54 (s, 2H), 4.00 (s, 3H).[0134] 1-Methyl-2-methoxy-4-nitrobenzene (1.2 g, 7.2 mmol) and bromosuccinimide (1.4 g, 7.8 mmol) were suspended in 80 mL of CCl 4. The solution was photolyzed overnight with a 300 watt lamp. The reaction solution was washed with saturated NaCl solution (3 20 mL) and dried over anhydrous Na 2SO 4. After evaporation, the residue was purified by flash silica gel column chromatography (hexanes/EtOAc, 10:1) to afford 2-methoxy-4-nitrobenzyl bromide as a light yellow oil (1.22 g, 69%). 1H NMR (CDCl 3, 200 MHz) delta 4.02 (s, 3H), 4.56 (s, 2H), 7.51 (d, 1H, J=8.4 Hz), 7.75 (d, 1H, J=2.2 Hz), 7.84 (dd, 1H, J=2.2, 8.4 Hz). (20.2 g, 118 mmol) was dissolved in 500 ml of anhydrous DCE, Ar was bubbled through the mixture for 5 min. N- b ro mo s u cc i n i m i de (23.2 g, 129 mmol) was added to the flask and stirred for 5 min. Benzoyl peroxide (1.89 g, 5.85 mmol) was added to the flask and stirred for 5 min. The flask was heated to 90 C and a lamp was angled toward the flask for direct illumination. The reaction mixture was stirred for 24 h under Ar. The mixture was then cooled to room temperature. The mixture was poured into a one liter separatory funnel and washed with fTO (100 ml). The aqueous layer was extracted with CH2CI2 (3 x 50 ml). The combined organic extracts were washed with brine (250 ml), dried over Na2S04, filtered, and concentrated under vacuum. The crude mixture was separated by flash column chromatography on silica gel using a EtOAc:Hexanes gradient from 0 % EtOAc to 10% EtOAc. Yield 13.1 g (45%). 1 H NMR (400 MHz, Chloroform-d) d 7.82 (dd, J = 8.3, 2.2 Hz, 1H), 7.74 (d, J = 2.1Hz, 1H), 7.49 (d, J = 8.3 Hz, 1H), 4.54 (s, 2H), General procedure: To a solution of substituted toluene in carbon tetrachloride were added N-bromosuccinimide (1.1 equiv) and 2, 2'-azobis(isobutyronitrile) (0.15 equiv). The mixture was refluxed, then filtered and concentrated. The residue was purified by silica gel column chromatography to give the target compound.

Used as medicine, dye and pesticide intermediate

Molecular Weight:167.16
XLogP3:2.6
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:167.058243149
Monoisotopic Mass:167.058243149
Topological Polar Surface Area:55
Heavy Atom Count:12
Complexity:166
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes