4-Bromo-2,5-Dimethoxybenzaldehyde Proposal.

anime · Thu Apr 28, 2005 1:37 am

There are two starting points.

1. Hydroquinione.
2. Dimethoxybenzene

1.) Hydroquinone is methylated dimethoxybenzene via DMS, CH3I, TMP or betaine/CaO.
2. The dimethoxybenzene is monobrominated using a known bromination method.
3. The 1-bromo-2,5-dimethoxybenzne is bromomethylated/chloromethylated to yield a 4-bromo-2,5-dimethoxybenzyl halide. (This benzyl halide compound is a lachrymator. Wear gloves. Keep away from eyes.)
4. A sommelet reaction is performed on the benzyl halide to yield the aldehyde.

A few questions I have.

A. How would one go about seperating the 4-bromo-2,5-dimethoxybenzyl halide from the 6-bromo-2,5-dimethoxybenzyl halide that could occur during the reaction.
B. Can the sommelet be performed on compounds containing aryl halides. (ie the 4th position bromine) w/o reacting.
C. Concerning purification of the aldehyde, distillation or bisulfite adduct?

Nicodem · Thu Apr 28, 2005 8:32 pm

anime · Thu Apr 28, 2005 9:03 pm

Nicodem, what method do you recommend. Swim was going to attempt a hydrolysis on the benzyl halide to yield a benzyl alcohol and then oxidize the benzyl alcohol to the aldehyde. The other alternative was reaction with vanadium pentoxide and peroxide for the oxidation. (Swim doesn't want to work with the vanadium unless he has to).

It is true about the benzyl halide, but if working without gloves very little of this compound is needed to induce irritation.

For the formation of the bisulfite adduct, couldthe same proceedure at the hive for the formation of MDP2P be followed?

I was thinking vacuum distillation, but I couldn't find an msds on the compound.

tetraedr · Thu Apr 28, 2005 11:30 pm

SWIM has been made something like this.
From hydroquinone
1. 1,4-dimethoxybenzene
2. 4-brom-2,5-dimethoxybenzene
3. 4-brom-2,5-dimethoxybenzaldehyde via Wielsmeer formylation.

I can present here all the procedures - I needs some time for translation.

But there was a problem for the next stage - Henry reaction with nitromethane. SWIM has got the brown liquid mixture, contains 4 spots in TLC. But he did not make more attempts, because he purchased 2,5-dimethoxybenzaldehyde and put off this problem for the future....

anime · Fri Apr 29, 2005 12:38 am

Swim just found an interesting methylation article using DMC to methylate gallic acid to 3,4,5-trimethylbenzoic acid. Smile

1,4-dimethoxybezene can be had in 4 hours using this method with total conversion of hydroquinone.

I am unfamiliar with the Wielmeer formylation. The proceedure would be great to have.

What catalyst did you use for the hendry reaction?
Rxn Update:

A bromomethylation was performed on 4-bromo-2,5-dimethoxybenzene. Instead of a solid product forming, an orange 'paste' like substance was formed. This substance had a pungent odor. Swims' assuming it was the benzyl bromide that had formed. The substance was then hydrolysed in an NaOH solution and a much lighter yellow, substance was formed that did not carry the same pungent odor.

Swim will attempt an oxidation on the substance when time allows. Swim is positive that this yellow substance is the benzyl alcohol.

Has anyone attempted a bromomethylation on 4-bromo-2,5-dimethoxybenzene?

Sandmeyer · Fri Apr 29, 2005 7:49 pm

anime · Fri Apr 29, 2005 8:51 pm

oh yea, haha I am familiar with that formylation, the spelling confused me.

Nicodem · Fri Apr 29, 2005 11:35 pm

The DMSO/NaHCO₃ oxidation of the crude 4-Br-2,5-diMeO-benzylchloride gives a 50% yield after the bisulphite purification. Considering that the crude chloromethylation product contains up to 15% of the diarylmethylenic side product and the ease and speed it is certainly one of the best methods available.

The nitrostyrene with MeNO2 can be made by the usual ammonium acetate method (see under 2C-H in PIHKAL). It is of orange color.

IndoleAmine · Dreamreader Deluxe

Make the nitrostyrene with ethylenediamine diacetate (EDDA), its as easy as making instant coffee Laughing

:

just dissolve aldehyde/coffee in enough hot IPA/water, add 1.1x molar amnt. of nitromethane/milk, spice up with 0.1x molar amnt. EDDA/sugar, stir for some time until the color is orange/cream and you have 2,5-dimethoxyphenyl-2-nitroethene/instant coffee... Wink

(really exactly the same - both reactions give ca. 95% yield, the only difference is that the henry rxn needs some more stirring compared to instant coffee....)

Hope you are thankful for the large amount of work I put into this field of comparative chemistry! Very Happy

Vitriodor · Wed May 04, 2005 12:09 am

I sure do appreciate you work I_A! My coffee never tasted better than the one I just made with your recipe. Wink

Now I only have to find EDDA to try the other suggestion...

tom-a-rom-rinbow · Fri May 13, 2005 12:52 pm

Nicodem- in your opinion is the standard chloromethylation procedure CH3O/ZnCl2/HCl(g) followed by NaHCO3/DMSO oxidation of the benzyl chloride a more reliable pathway than Riemer Tiemann on 4-methoxyphenol? i presume the oxidation uses an excess of NaHCO3, and enough DMSO? what is the temperature/duration?

i imagine much unreacted 4-Br-2,5-dimethoxybenzene can be recycled from the chloromethylation reaction as forerun?

would intermediate 4-Br-2,5-dimethoxybenzene or 2,5-dimethoxybenzene need to be purified by distillation if these are produced by, say, Br2/AcOH/DCM and DMS respectively?