2-BROMO-6-METHYL-4-NITROANILINE

yellow needles

To a suspension of 2-methyl-4-nitroaniline (10.0 g, 65.7mrnol) in glacial acetic acid (100 rnL) at 20 °C was added bromine (3.4 mL, 66 rnmoi) dropwiseover 40 mm. The mixture was stirred at 20 °C for another 30 mm. Then water (100 rnL) was added, and the resulting precipitate was collected by filtration and dried in vaeuo at 80 °C for 6 h to yield the title compound (14.1 g, 99percent) as a yellow solid. MS (ESi): mass calcd. for C7HBrN2O2 23 0.0, m/z found 231 [M+Hft. ‘H NMR (300 MHz, DMSO-d6) ö 8.13 (d, J = 2.2 Hz, iH), 7.89 (d, J= 1.5 Hz, IH), 6.48 (s, 2H), 2.22 (s, 3H).To a solution of 2-methyl-4-nitroaniline (2.0 g, 13.2 mmol) inacetonitrile (40 mL) was added N-bromosuccinimide (2.8 g, 15.8 mmol) at 60 C. The mixture was heated to reflux for 3 h andthen cooled to room temperature. The mixture was evaporated anddiluted with dichloromethane (50 mL). The organic layer waswashed with 2.5MNaOH and brine, dried over Na2SO4, filtered, andevaporated. The residue was purified by silica gel chromatography(n-hexane/ethyl acetate, 4/1, v/v) to give 2-bromo-6-methyl-4-nitroaniline as a yellow solid (2.75 g, 91percent). Mp: 178e179 C. Rf:0.40 (n-hexane/ethyl acetate, 5/1, v/v). 1H NMR (DMSO-d6, 400 MHz) d 8.15 (d, J 2.5 Hz, 1H), 7.93 (d, J 2.1 Hz, 1H), 6.53 (s, 2H), 2.23 (s, 3H). MS (ESI) m/z:228.5 [MH]-.To a suspension of 2-methyl-4-nitroaniline (10.0 g, 65.7mrnol) in glacial acetic acid (100 rnL) at 20 C was added bromine (3.4 mL, 66 rnmoi) dropwiseover 40 mm. The mixture was stirred at 20 C for another 30 mm. Then water (100 rnL) was added, and the resulting precipitate was collected by filtration and dried in vaeuo at 80 C for 6 h to yield the title compound (14.1 g, 99%) as a yellow solid. MS (ESi): mass calcd. for C7HBrN2O2 23 0.0, m/z found 231 [M+Hft. 'H NMR (300 MHz, DMSO-d6) oe 8.13 (d, J = 2.2 Hz, iH), 7.89 (d, J= 1.5 Hz, IH), 6.48 (s, 2H), 2.22 (s, 3H).To a solution of 2-methyl-4-nitroaniline (2.0 g, 13.2 mmol) inacetonitrile (40 mL) was added N-bromosuccinimide (2.8 g, 15.8 mmol) at 60 C. The mixture was heated to reflux for 3 h andthen cooled to room temperature. The mixture was evaporated anddiluted with dichloromethane (50 mL). The organic layer waswashed with 2.5MNaOH and brine, dried over Na2SO4, filtered, andevaporated. The residue was purified by silica gel chromatography(n-hexane/ethyl acetate, 4/1, v/v) to give 2-bromo-6-methyl-4-nitroaniline as a yellow solid (2.75 g, 91%). Mp: 178e179 C. Rf:0.40 (n-hexane/ethyl acetate, 5/1, v/v). 1H NMR (DMSO-d6, 400 MHz) d 8.15 (d, J 2.5 Hz, 1H), 7.93 (d, J 2.1 Hz, 1H), 6.53 (s, 2H), 2.23 (s, 3H). MS (ESI) m/z:228.5 [MH]-.[0646] Step 1: 2-Methyl-4-nitro-6-(prop-1-en-2-yl)aniline. A mixture of 2- isopropenylboronic acid, pincol ester (6.84 g, 40.7 mmol, Combi-Blocks, San Diego, CA), 2- amino-3-bromo-5-nitrotoluene (4.7 g, 20.34 mmol), sodium carbonate (anhydrous, powder; 2.56 mL, 61.0 mmol), tetrakis(triphenylphosphine)palladium(0) (2.35 g, 2.03 mmol) in 1, 2- dimethoxyethane (100 mL) and water (25 mL) was stirred under N2(g) at 80 C for 18 h. The mixture was then diluted with satd. aq. NaHCO3 (150 mL) and extracted with EtOAc. The combined extracts were dried over Na2SO4 and concentrated in vacuo. Chromatographic purification of the residue (silica gel, eluent: 0-10% MeOH/DCM) furnished 2-methyl-4-nitro- 6-(prop-1-en-2-yl)aniline (3.28 g, 17.1 mmol, 84 % yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) d ppm 7.92 (d, J=2.1Hz, 1H), 7.86 (d, J=2.5 Hz, 1H), 5.41 (t, J=1.7 Hz, 1H), 5.11 (s, 1H), 2.23 (s, 3H), 2.08 (s, 3H), 1.53 (br s, 2H). m/z (ESI, +ve ion): 192.9 (M+H)+.

Molecular Weight:231.05
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:229.96909
Monoisotopic Mass:229.96909
Topological Polar Surface Area:71.8
Heavy Atom Count:12
Complexity:183
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes