Sciencemadness Discussion Board

3-methoxy-4-bromobenzaldehyde

Formula409 - 4-9-2009 at 18:50

Trying to find or come up with some sort of preparation of this compound. I've found references for several of the steps I have proposed, but some references don't deal with the specific compounds.

Here is the proposed route from toluene:

The only step I am unsure of as of now is that nitration and where the group would go. Unsubstituted benzaldehyde gets substituted primarily in the meta position, however I am unaware as to what effect the bromine atom has. I've thought about whether it is possible to nitrate m-hydroxybenzaldehyde at the para position, reduce to an amine and then swap the amine for a bromine atom by this procedure: http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv1...
however I am once again unsure as to where the ring would be substituted, presumably not in the para position, but the other meta position.

Can you guys suggest any improvements/potential problems with the routes that I have selected? I have no access to literature searches so obviously my only information sources are patents and the extensive Rhodium archive. I'm trying to do this with (relatively) available materials.

If anyone has more specific references, then I am more than happy to hear, well read them!

Refs:
[1] http://www.sciencemadness.org/talk/viewthread.php?tid=6882
[2] http://www.sciencemadness.org/talk/files.php?pid=86142&a...
[3] http://www.orgsyn.org/orgsyn/prep.asp?prep=CV2P0089
[4] http://www.erowid.org/archive/rhodium/chemistry/aromatic.bro...
[5] http://www.sciencemadness.org/talk/viewthread.php?tid=11720#...
[6] http://www.erowid.org/archive/rhodium/pdf/phenol.nitration.p...
[7]Vogel’s
[8] http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv2...

I can post more detailed procedures, however why regurgitate already published procedures?

Formula409.

[Edited on 5-9-2009 by Formula409]

Formula409 - 4-9-2009 at 18:52

Edit: Can this please be moved to the "organic chemistry" forum? I was going to post it here before I did some peeking around!

Formula409.

Klute - 4-9-2009 at 19:23

None of your brominating refs are revelant: no where is benzaldehyde brominated. It will not brominate at the para position.

Bromination of 3-methoxybenzaldehyde should give your seeked product. This aldehyde can be prepared by methoxylation of m-bromobenzaldehyde, the product obtained by carefull bromination of benzaldehyde.

A lengthy way from vanillin would be the following: turn the phenol into an amine (http://www.freepatentsonline.com/5214210.html), hydrolyze the formed aldimine, diazotize and react with CuBr. Should work, might need to check the amination procedure as the conditions might be a bit harsh for the aldehyde.

Otherwise formylation of 2-bromoanisole will give a mixture of isomers, your product being the minor one I suppose.

[Edited on 5-9-2009 by Klute]

Formula409 - 4-9-2009 at 20:05

Quote:
None of your brominating refs are revelant: no where is benzaldehyde brominated. It will not brominate at the para position.

My mistake, however brominating toluene and then oxidising should be find should it not?
Quote:

Bromination of 3-methoxybenzaldehyde should give your seeked product. This aldehyde can be prepared by methoxylation of m-bromobenzaldehyde, the product obtained by carefull bromination of benzaldehyde.

According to the attached paper, iodination of 3-methoxybenzaldehyde yields 3-methoxy-6-iodobenzaldehyde. Nichols says that bromination of m-hydroxybenzaldehyde gives 2-bromo-5-hydroxybenzaldehyde [9].
Quote:

A lengthy way from vanillin would be the following: turn the phenol into an amine (http://www.freepatentsonline.com/5214210.html), hydrolyze the formed aldimine, diazotize and react with CuBr. Should work, might need to check the amination procedure as the conditions might be a bit harsh for the aldehyde.

Vapour-phase sounds a bit out of the question though.

[9]http://www.erowid.org/archive/rhodium/chemistry/bromomethoxyamph.nichols.html

I'll update the original post in order to correct my mistake. Thanks for pointing that out!

Formula409.

[Edited on 5-9-2009 by Formula409]

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