Chemical Properties
Colorless Oil
Biological Activity
1-BROMO-3-METHOXY-5-METHYLBENZENE is an inhibitor of the phenolic acid transporter (PAT). In vitro studies have shown that 1-BROMO-3-METHOXY-5-METHYLBENZENE inhibits the transport of phenolic acids across the cell membrane, which prevents their uptake and accumulation in cells. It has been shown to inhibit the growth of Aspergillus niger and other fungi. It also has cytotoxic effects on human cells in culture, which may be due to its ability to inhibit fatty acid biosynthesis and disrupt intramolecular interactions with the dibenzofuran ring.
Synthesis
The general procedure for the synthesis of 1-bromo-3-methoxy-5-toluene from 4-bromo-2-methoxy-6-methylaniline was as follows: in a 250 mL round-bottomed flask, 4-bromo-2-methoxy-6-methylaniline (5.8 g, 26.84 mmol) was dissolved in acetic acid (49 mL), followed by the addition of concentrated hydrochloric acid (5.6 mL). A 7 mL aqueous solution of sodium nitrite (2.19 g, 31.78 mmol) was slowly added dropwise to the reaction mixture at 0 °C. After the dropwise addition, the reaction mixture was continued to be stirred at 0 °C for 30 min. Subsequently, 50% aqueous hypophosphite solution (56.5 mL) was added at 0 °C. The reaction mixture was stirred at 0 °C for a period of time and then gradually warmed up to room temperature and stirred overnight. After completion of the reaction, ethyl acetate was added for extraction and the organic phase was washed with saturated sodium bicarbonate solution. The organic layer was concentrated and purified by silica gel column chromatography (eluent: 100% hexane) to give a pale liquid product (5.12 g, 95% yield). The 1H NMR (300 MHz, CDCl3) data of the product were as follows: δ 6.97 (s, 1H), 6.87 (s, 1H), 6.64 (s, 1H), 3.80 (s, 3H), 2.36 (s, 3H).
References
[1] Patent: WO2009/5674, 2009, A2. Location in patent: Page/Page column 423
[2] Patent: US2010/204234, 2010, A1. Location in patent: Page/Page column 13-14
[3] Chemistry - A European Journal, 2005, vol. 11, # 3, p. 951 - 959
[4] Journal of Medicinal Chemistry, 2001, vol. 44, # 12, p. 1866 - 1882
