3-methyl-1,4-dimethoxybenzene bromination

[Bandil]

After reading the excellent post by antoncho regarding sodiumethoxide production swim was getting interested.

If one accidently found alot of 3-methyl-1,4-dimethoxy lying around and wanted to brominate iodinate it. Would it be as simple as adding elemental bromine to a soln. of 3-methyl-1,4-dimethoxy? Swim was of course looking for the 4-methyl-2,5-dimethoxy-bromobenzene as a product, so he could fool around with some acetone enolate and make some 4-methyl-2,5-dimethoxy-P2P... Or are the ring substitutens arranged so that the bromine would attack elsewhere?

Thanks
Regards
Peter

[yellium]

Shameless plug:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/2cbde.html

http://www.erowid.org/library/books_online/pihkal/pihkal023.shtml

https://www.thevespiary.org/rhodium/Rhodium/chemistry/stp.html

But I guess BuLi and POCl3 are out of reach, otherwise you wouldn't want to brominate it...

[Bandil]

The first post(i think it was the first) said a bromination of 3-methyl-1,4-dimethoxybenzede yeilded the correct positioned brominated product. Could elemental bromine be used insted? Swim would think so, but is quite interessted in the opinion of the other bees.

After the bromination swim was thinking of the reaction with acetone w/ sodiumethoxide to give the corr. P2P. Is that reaction as easy as adding the NaOCH2CH3 to acetone and carfully adding the brominatied agent?

Thanks alot!

Regards
Peter

[yellium]

See preparation of DESOXY (#52) to get the feel for how to deal with brominations with bromine.

http://www.erowid.org/library/books_online/pihkal/pihkal052.shtml

Regarding brominations: keep in mind that you'll always have some stuff dibrominated, and some stuff not brominated. To increase the fraction of monobrominated stuff, some synths use 1.05 or 1.1 equivalent bromine instead of 1.0. Also, keep your math straight! Once, I did a bromination with 2.0 equivalent bromine instead of 1.0. Aaaargh!

An other option is to try to make the aldehyde with a grignard, and then follow the traditional route. Grignard will be difficult to start, if at all.