preparation of 3,4,5-trimethoxybromobenzene_kain industrial additive

background and overview^[1]

3,4,5-trimethoxybromobenzene can be used as a pharmaceutical synthesis intermediate. it can be prepared by the reaction of 5-bromo-1,2,3 trihydroxybenzene and dimethyl sulfate, or it can also be prepared from 4-bromo-2 , 6-dimethoxyphenol was prepared as the reaction raw material.

preparation^[1-2]

option 1,

cool the mixture of 5-bromo-1,2,3 trihydroxybenzene (1.3g, 5.63mmol), 1m naoh (14ml) and dimethyl sulfate (800μl, add 16.89mmol) to 10°c. the mixture was heated to reflux for 3 hours, then another portion of dimethyl sulfate (800 μl) was added. the mixture was heated under reflux for another 3 hours, the mixture was cooled overnight, and the gray solid was filtered off, then dissolved in 50 ml of diethyl ether, with 5% naoh-h₂o, water, brine washed, then dried (mgso₄) and concentrated to give 3,4,5-trimethoxybromobenzene (1.39g, 76%). ¹hnmr (cdcl₃) δ6.72 (s, 2h), 3.85 (s, 6h), 3.82 (s, 3h); m/z. ¹³cnmr (cdcl₃) 136.67, 137.11, 115.92, 108.07, 60.58, 56.05.

option 2,

cool a mixture of 74g (0.32mol) 4-bromo-2,6-dimethoxyphenol and 32g (0.8mol) naoh in 850ml h₂o to 10° c, then add 45 ml (0.48 mmol) of dimethyl sulfate, reflux the mixture for 3 hours, and then add an equal amount of dimethyl sulfate (0.96 mol in total). the mixture was refluxed for another 3 hours. after cooling overnight, the gray product solidified and was filtered out and dissolved in 1.21 ether. the ether solution was filtered to remove insoluble impurities, and was sequentially treated with 5% naoh solution (200ml), water (2 × 200ml). ) and washed with brine (200 ml). the ether phase was dried over na₂so₄ to obtain an off-white solid, which was recrystallized in hexane (300 ml) to obtain 62.3 g (79%) of 3,4 , 5-trimethoxybromobenzene.

references

[1]us2003176478

[2] cn01819067.7 ortho-substituted chiral phosphines and trivalent phosphonates and their use in asymmetric catalytic reactions