Synthesis
General procedure for the synthesis of 2-iodo-6-nitrotoluene from 2-methyl-3-nitroaniline:
4.1.10. Synthesis of 2-methyl-3-nitroiodobenzene (26)
Concentrated sulfuric acid (8 mL) was added to a solution of 2-methyl-3-nitroaniline (25) (5.00 g, 32.9 mmol) in water (50 mL). The reaction mixture was cooled to 0 °C and a solution of sodium nitrite (2.49 g, 36.2 mmol) in water (5 mL) was added slowly and dropwise. After the dropwise addition, the reaction mixture was continued to be stirred for 1 hour. Subsequently, a solution of potassium iodide (8.18 g, 49.3 mmol) in water (20 mL) was added slowly dropwise and stirring was continued for 1 hour after completion of the dropwise addition. Upon completion of the reaction, the reaction mixture was extracted with dichloromethane (330 mL). The organic phases were combined, washed with saturated aqueous sodium thiosulfate (Na2S2O3), dried over anhydrous sodium sulfate (Na2SO4), and concentrated under reduced pressure to remove the solvent to give the crude product. The crude product was purified by column chromatography with ethyl acetate/petroleum ether (1:10) as eluent to afford the target product 2-iodo-6-nitrotoluene as a yellow solid (7.43 g, 85% yield); melting point 36-37 ° C.; infrared spectra (thin-film method, cm1 ): 3082, 1591, 1519, 1443, 1348, 1273, 1204, 1087, 1001, 860, 794, 735, 696; 1H NMR (400 MHz, CDCl3): δ 2.52 (3H, s, CH3), 6.96 (1H, t, J = 8.0 Hz, aromatic hydrogen, H5), 7.64 (1H, dd, J = 8.0, 1.2 Hz, aromatic hydrogen, H6), 7.80 (1H, dd, J = 8.0, 1.2 Hz, aromatic hydrogen, H6), 7.80 (1H, dd, J = 8.0, 1.2 Hz). J = 8.0, 1.2 Hz, aromatic hydrogen, H4); 13C NMR (100 MHz, CDCl3): δ 25.0 (CH3, ArCH3), 103.6 (quaternary, aromatic carbon, C1), 123.9 (aromatic hydrogen, C4), 128.0 (aromatic hydrogen, C5), 135.0 (quaternary, aromatic carbon, C2), 143.1 (aromatic hydrogen, C6), 150.4 (quaternary, aromatic carbon, C2), 143.1 (aromatic hydrogen, C2), 143.1 (aromatic hydrogen, C2), 150.1 (aromatic hydrogen, C2), 150.1 (aromatic hydrogen, C2), 150.1 (aromatic hydrogen, C2) C6), 150.4 (quaternary carbon, aromatic carbon, C3); mass spectrum (EI): m/z 262.9439; theoretical value of C7H6INO2 (M) 262.9443.
References
[1] Chemical & Pharmaceutical Bulletin, 1986, vol. 34, # 9, p. 3971 - 3973
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 11, p. 3177 - 3180
[3] Chemical Communications, 2015, vol. 51, # 6, p. 1070 - 1073
[4] Tetrahedron, 2013, vol. 69, # 2, p. 758 - 769
[5] Patent: US2010/75952, 2010, A1. Location in patent: Page/Page column 89
