Chemical Properties
Colorless to Yellow liquid
Uses
4-Bromoveratrole is a metabolite of bromobenzene, with a catechol moiety in the substructure. It also has use as a redox shuttle additive, essentially a component in lithium batteries that consumes excess current during overcharge. It is also used in the synthesis of the isoquinoline alkaloid (-)-mesembrine.
Biological Functions
4-Bromoveratrole has been shown that this molecule binds to the receptor for acetylcholine, which is found in the central nervous system and on muscles. The binding of 4-bromoveratrole to this receptor leads to the release of chloride ions from the cell, which increases the activity of acetylcholine. The detection sensitivity of 4-bromoveratrole in solution was determined by adding malonic acid or hydrochloric acid, which led to an increase in fluorescence intensity. This molecule also has fatty acid and hydroxyl groups that have been shown to have anti-inflammatory properties.
Synthesis
Example 1: Preparation of 4-bromo-1,2-dimethoxybenzene from veratrole ether
(1) An acetic acid solution (1.6 L) of veratrole ether (142 g, 1.03 mol) and ammonium bromide (110 g, 1.12 mol, 1.10 eq.) was added to a 3.0 L reactor.
(2) Aqueous hydrogen peroxide solution (30%, 180 mL, 1.76 mol, 1.67 eq.) was slowly added dropwise to the reaction mixture and the reaction system was continuously stirred at room temperature.
(3) After 20 hours of reaction, the reaction was quenched with saturated sodium bicarbonate solution and the reaction mixture was extracted with dichloromethane (3 x 200 mL).
(4) The organic phases were combined, washed sequentially with water (2 x 200 mL) and saturated saline (200 mL), and dried over anhydrous sodium sulfate.
(5) Concentrate the organic phase under reduced pressure to obtain a yellow crude product.
(6) The crude product was purified by decompression distillation and the fraction with boiling point 128-133 °C/10 mbar was collected to obtain 4-bromo-1,2-dimethoxybenzene (202.7 g, 91% yield).
(7) The structure of the product was confirmed by NMR hydrogen (400 MHz, DMSO-d6) and carbon (100 MHz, DMSO-d6) spectra: 1H NMR δ: 7.50 (d, J=8.4 Hz, 1H), 6.90 (d, J=2.0 Hz, 1H), 6.80 (dd, J=8.4, 2.0 Hz, 1H), 3.85 (s, 3H ), 3.80 (s, 3H); 13C NMR δ: 150.3, 148.8, 123.5, 115.3, 113.8, 112.3, 56.2, 56.0.
References
[1] Journal of Chemical Research - Part S, 1998, # 10, p. 662 - 663
[2] Organic Letters, 2017, vol. 19, # 16, p. 4243 - 4246
[3] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 2, p. 591 - 593
[4] Tetrahedron Letters, 2001, vol. 42, # 39, p. 6941 - 6942
[5] Heterocycles, 1995, vol. 41, # 5, p. 893 - 896
