Synthesis
In a jacketed reactor, acetic acid (450 mL) and acetic anhydride (225 mL) were added sequentially at 10 °C. Under stirring conditions, sodium periodate (NaIO4, 97.2 g) and iodine (I2, 77.2 g) were added to the above mixture in batches. The reaction temperature was controlled to be lower than 30°C and concentrated sulfuric acid (H2SO4, 720 mL) was added slowly and dropwise. Subsequently, o-chloronitrobenzene (2-chloronitrobenzene, retention time Rt = 11.11 min) was added all at once and the reaction mixture was gradually warmed up to 64°C. The reaction mixture was stirred continuously for at least 2 hours until process monitoring indicated that the reaction was essentially complete. Upon completion of the reaction, the mixture was cooled to room temperature and slowly transferred to another jacketed reactor containing pre-cooled sodium sulfite solution (Na2SO3, 250 g dissolved in 2000 mL of water). The wet filter cake was collected by filtration and washed with cold water (450 mL × 2). Finally, the filter cake was purified by crystallization with n-heptane to afford 2-chloro-5-iodonitrobenzene (2-chloro-5-iodonitrobenzene) in 62% yield and 98% purity by HPLC (Rt = 15.75 min). The structure of the product was analyzed by 1H NMR (400 MHz, CDCl3) δ 7.26-6.29 (m, 1H), 7.81-7.84 (dd, J = 8.4, 2.0 Hz, 1H), 8.17-8.16 (d, J = 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 90.5, 127.0, 133.2, 134.1, 142.1, 148.3; MS (ESI): m/z 282.9 (M) Confirmed.
References
[1] Patent: US2014/66634, 2014, A1. Location in patent: Paragraph 0026; 0027
[2] Patent: WO2014/37307, 2014, A1. Location in patent: Page/Page column 10
[3] Journal of the American Chemical Society, 1953, vol. 75, p. 4265,4266
[4] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1973, p. 595 - 599
[5] Journal of Heterocyclic Chemistry, 2009, vol. 46, # 5, p. 936 - 948
