Sciencemadness Discussion Board - 2,5-Dimethoxybenzaldehyde to 4-Alkyl-2,5-Dimethoxybenzaldehyde ?

2,5-Dimethoxybenzaldehyde to 4-Alkyl-2,5-Dimethoxybenzaldehyde ?

Dextrose - 14-10-2006 at 12:29

Bromination of 2,5-DMBA yields 4:1 of the 4-Br and 6-Br isomers. Further refluxing with alkylthiols and K2CO3 in DMF will yield the corresponding 2C-T-x aldehyde. (Rhodium)

Another method for iodination of 2,5-DMA/2C-H to DOI/2C-I using I2/nitrate-salt gives the 4-Iodo product in good yiels. (Rhodium)

Could it be possible to iodinate 2,5-DMBA to 4-I-2,5-DMBA, then reflux with ex. ethyl-iodide with AlCl3 in DCM or DMF to yield the corresponding 4-alkyl-2,5-DMBA ?

Alkyl-iodides are easily prepared from the corresponding alkyl-alcohol using I2 and red phosphorous. (Rhodium)

Thanks in advance!

[Edited on 14-10-2006 by Dextrose]

not_important - 14-10-2006 at 22:52

You mean RI + ArI ==(AlCl3)==> R-Ar + I2 ? Not really

RI + ArBr + 2Na ==> R-Ar + NaI + NaBr Wurtz-Fittig reaction. If R is fairly small use an excess of it and sodium, R-R should be easy to distill away..

RBr + ArH ==(AlCl3)==> R-Ar + HBr that's standard FC, note that the carbonyl oxygen complexes with AlCl3 so you need more moles AlCl3 than there are of aldehyde, and some cases the aldehyde function gets trashed (don't know in your case)

The 2C-T is R-S-H + ArBr + K2CO3 ==> R-S-Ar + KBr + H2O + CO2 (non-balanced)

Sandmeyer - 17-10-2006 at 11:56

I suppose you want the one with a methyl. With 2,5-dimethoxybenzaldehyde at hand, consider trying modified Clemmensen (UTFSE for "Sandmeyer" and "Clemmensen") to reduce it to the toluene. The usual repertoair follows after that. Red-al is a suitable reductant for this purpose, being multifunctional in this route. Precursor for the higher homologs (from 2,5-dimethoxybanzaldehyde) can be imagined in two steps: 1.) Wittig (or some variation) 2.) Hydrogenation.

[Edited on 17-10-2006 by Sandmeyer]

Dextrose - 20-10-2006 at 10:19

Thank you for your replies.

I've read Carey's book about nucleophilic substitution (chapter 8) with alkyl bromides in present of the lewis base, so would it be possbible to alkylate 4-Br-2,5-DiMeOBAH this way?

If alkylthiols works for preparing 2C-T-x aldehydes, i could imagine this also would be possible.

Since DOM and 2C-D is illegal here, i'm mostly interested in the ethyl, propyl and perhaps amyl (interesting?) derivates.

Regards.

[Edited on 20-10-2006 by Dextrose]

Nicodem - 20-10-2006 at 10:24

4-bromo-2,5-dimethoxybenzaldehyde is not an alkyl bromide!
(Even if it was, what would you use as a synthon equivalent of a methyl nucleophile? A methyl grignard reagent? And what would prevent it from reacting with the carbonyl group?)
Besides Sandmeyer already gave you a viable route.

Dextrose - 20-10-2006 at 11:17

Sorry for my newbie-ism... i'm new to aromatic substitution.

How about af F/C acylation with 4-Br-2,5-DMBAH and Akylbromide with AlCl3 in DCM like the Sasha does on para-dimethoxybenzene with propionyl/acetyl chloride in the 2C-P/2C-E entries, then then making the phenethylamine, and reduce the propiophenone / acetophenone with Zn/HCl or Al/Hg ?

Maybe amine protection would be nessescary?

Is the aldehyde group deactivating enough for alkylbromides, since it work with alkylthiols?

Or could one condensate the aldehyde, then reduce the carbonyl-group and the nitrostyrene in the same step?

Thanks in advance!

Sandmeyer > I've searched McMurry and Careys, but can't seem to find the reactions... Will check Vogel's later.
If you could give me some references, i would be very thanksful!

[Edited on 20-10-2006 by Dextrose]

Nicodem - 20-10-2006 at 11:37

Please be more precise. Do you want to acylate or alkylate your substrate?

Where do you want to put the acyl/alkyl group? In 4-bromo-2,5-dimethoxybenzaldehyde (I assume your "4-Br-2,5-DMBAH" stands for this?) you already have the position 4 occupied, so you can only alkylate the positions 3 and 6. But Friedel-Crafts reactions on aldehydes are doomed to fail for obvious reasons. Furthermore, alkylchlorides with AlCl3 catalyst are more effective.

Dextrose - 20-10-2006 at 11:47

I want it on the 4. position.

Alkylation would be preffered.
Would this be ortho or para-dominant with alkyl chloride and AlCl3 on the 2,5-dimethoxybenzaldehyde?

Could 4-Br-DiMeOBAH be gassed with propane in DMF to yield the propyl-product?

R-Br + alkane -> R-alkyl + alkyl bromide ?

Thank your for posts!
I am using TFSE and my litterature as best as i can.

[Edited on 21-10-2006 by Dextrose]

Sergei_Eisenstein - 20-10-2006 at 11:49

The Wittig reaction and Clemmensen reduction are both in Carey's! Use the index.

There are quite some mistakes in your idea, e.g. the following: Or could one condensate the aldehyde, then reduce the carbonyl-group and the nitrostyrene in the same step? If you have two carbonyl functions in your theoretical molecule, both will react with the nitroalkane you want to use. The aldehyde will be more reactive since it is more accessible, but there usually is an excess of nitroalkane present. In case of nitromethane, it is sometimes used both as reactant and solvent. Also, even if the nitroalkane would only react with the carbonyl from the benzaldehyde, the ketonic carbonyl will be reduced to an alcohol when you reduce the nitrostyrene to an amine. And even if you would be able to reduce the nitrostyrene selectively, you'd have to protect the ketone as an acetal to prevent polymerization (condensation of the carbonyl with newly formed amine).

Nicodem - 20-10-2006 at 12:30

Quote:

Originally posted by Dextrose
Could 4-Br-DiMeOBAH be gassed with propane in DMF to yield the propyl-product?

This is too much for my patience. Please learn some basic organic chemistry before attempting any reaction at all. I estimate 75% of what you wrote up to now made little or no sense whatsoever. Even if you follow a published procedure you still need knowledge to perform any organic synthesis. It is not like making a cup of coffee.

Dextrose - 4-11-2006 at 18:28

Quote:

Originally posted by Nicodem

Quote:

Originally posted by Dextrose
Could 4-Br-DiMeOBAH be gassed with propane in DMF to yield the propyl-product?

Thanks for the bashing.

I'm well trained in laboratory techniques, but will quit and study full-on organic chemistry or other creative organic synthesis.

We don't have organic on this level at my current education, so sorry for the noob suggestions, only trying to use my brain.

I have experience with condensating and reduction, but not with aromatic substitution.

[Edited on 5-11-2006 by Dextrose]