1.3- Dimethoxybenzene bromination

To a stirred solution of 60 g of 2-ethylthio-1,3-dimethoxybenzene in 300 mL CH,C1, there was added 49 g elemental bromine dissolved in 100 mL CH2C12. 

To a stirred solution of 19.8 g of 2-(n)-propylthio-l,3-dimethoxybenzene in 200 mL CH,C12 there was added 15.4 g elemental bromine dissolved in 100 mL CH2C1,. The reaction was not exothermic, and it was allowed to stir for 1 h. The reaction mixture was washed with H,0 containing sodium hydrosulfite (which rendered it nearly colorless) and finally washed with saturated brine. The solvent was removed under vacuum leaving 3 3.5 g of apale yellow liquid. This was distilled at 112-120 °C at 0.3 mm/Hg to yield 4-bromo-2-(n)-propylthio-l,3-dimethoxy-benzene as a pale yellow oil. Anal. (CnH 5Br02S) C,H. 

Regioselective, high-yield, aromatic bromination and chlorination of mesitylene, 1,3-dimethoxybenzene, 2,3-dimethylanisole, o-xylene and thiophene derivatives is observed in solid/liquid systems where solid NBS or NCS, combined with perchloric acid catalyst, is contacted at room-temperature with an organic phase (CC14 or hexane) containing the substrate737. 

The third compound studied is the 4-thio analog of mescaline, 4-methylthio-3,5-dimethoxyphenethylamine. This was prepared (see scheme II) by the reaction, of lithiated m-dimethoxybenzene with dimethyldisulfide to form 2,6-dimethoxythioanisole. This underwent bromination uniquely adjacent to the methoxy group, and the resulting bromodimethoxythioanisole underwent a smooth benzyne reaction with acetonitrile to form the benzyl cyanide shown, which was reduced to the desired end product (3) with aluminum hydride in THF. 

The regioselectivity observed with many nucleophilic arenes is moderate to excellent, and generally follows the pattern expected for aromatic electrophilic substitution (e.g., nitration, bromination, etc.) of the arenes. 3-Methoxythiophene reacts first at the 2-position but double arylation at the 2- and 5-positions is achieved in the absence of DME additive. 2-Ethylthiophene, 2,3-dimethylfuran, and 2,2 -bithiophene react at the expected 5-position and, similarly, thiophene reacts at the 2-position. 1,3-Dimethoxybenzene reacts exclusively at the 4-position while... 

This method has also been used for the iodination of phenols and for the bromination of anisole to give 4-bromoanisole (87%), of 1,3-dimethoxybenzene to give 4-bromo-L3-dimethoxybenzene (80%). 

To a stirred solution of 60 g of 2-ethylthio-1,3-dimethoxybenzene in 300 mL CH2CI2 there was added 49 g elemental bromine dissolved in 100 mL CH2CI2. The reaction was not exothermic, and it was allowed to stir for 2 h. The reaction mixture was washed with H20, then with aqueous NaOH, and finally with H20 that contained sodium hydrosulfite. 

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