Synthesis
The general procedure for the synthesis of 3-fluoro-4-nitrobenzenesulfonyl chloride from 3-fluoro-4-nitroaniline is as follows: 3-fluoro-4-nitroaniline (15 g, 96.1 mmol, Combi Blocks) was dissolved in hydrochloric acid (120 ml) at 0°C, and sodium nitrite dissolved in water (10 ml) was slowly added (7.9 g, 115.0 mmol Qualigens). The reaction temperature was maintained at 0°C and the mixture was stirred for 30 min. Subsequently, the resulting diazonium salt solution was added dropwise to a pre-cooled solution of copper(II) chloride dihydrate (14.4 g, 96.1 mmol, Aldrich) in acetic acid (80 ml), while sulfur dioxide gas was passed to saturation. The reaction mixture was continued to be stirred at 25°C for 1 hour. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the mixture was poured into ice-cold water and the solid product was precipitated. The solid was collected by filtration, washed with water and dried in air to afford 14.2 g of 3-fluoro-4-nitrobenzenesulfonyl chloride as a brown solid in 62% yield. The structure of the product was confirmed by 1H-NMR (400 MHz, DMSO): δ 8.29 (t, J = 7.2 Hz, 1H), 8.01 (dd, 2H).
References
[1] Patent: WO2013/122897, 2013, A1. Location in patent: Page/Page column 175; 176
[2] Helvetica Chimica Acta, 1983, vol. 66, # 1, p. 68 - 75
[3] Patent: WO2003/76413, 2003, A1. Location in patent: Page/Page column 28-30
[4] Patent: WO2017/156181, 2017, A1. Location in patent: Paragraph 00359
