[darkdevil]

Dear,
I have been doing the bromination of 3-hydroxybenzaldehyde. I followed a reported procedure and conditions which it claims they can convert the substrate to product up to 87% yield with one isomer as major product. Since they do not have a detailed procedure, I can only obtain ~ 18% yield.
I wonder if the bromine solution shall be added slowly or in a single portion.

Here are the procedures and conditions:
1) Dissolving 5g 3-hydroxybenzaldehyde in 50mL chloroform (do not dissolve well)
2) Adding Br₂ (1 eqv. w.r.t. substrate) in 30 mL chloroform to the above solution
3) Wait 1 hour for reaction
4) Work-up

Do I need to do the reaction under inert atmosphere?
I did a TLC after 1 hour and I still see plenty of my starting material spot. and I can assume only 30-40% was converted to my product by comparing the TLC spots intensity under UV lamp. The chemistry is correct after i do the purification and confirmed with proton NMR, only the yield is much much lower than the literature.

I am thinking of doing the reaction again under N₂, and use a dropping funnel to deliver the Br₂. I also want to ask if I can increase the Br₂ stoichiometry? Will it lead to dibromo products? And how about the poor solubility of my aldehyde in CHCl₃? But after 1 hour the reaction was homogeneous.

Thanks a lot!!!

[discodermolide]

Temperature? What did you use?

[Dan]

Did the solution decolourise?

If there is still bromine left after 1 hour, leave it for longer.

what is your product distribution? Any side products?

[darkdevil]

I did it at room temperature just like the paper did
I can get a single product and easily purified by crystallization (surprisingly clean and pure in NMR). But i recovered a lot of starting materials

[darkdevil]

Did the solution decolourise?

If there is still bromine left after 1 hour, leave it for longer.

what is your product distribution? Any side products?

- The bromine decolorize when I add it dropwise
- If added in one portion, it decolorizes very very slowly even after 1 hour. But the product is also brown in color so I am not sure if decoloration is a good way to monitor the progress. One more thing is, its side product is HBr, so  does it mean If I remove HBr I can shift the equilibrium further to product side? But how can I do so?

[discodermolide]

Add the bromine over a longer period, say 90 minutes and see if the yield gets better.

[darkdevil]

Add the bromine over a longer period, say 90 minutes and see if the yield gets better.

Tried. It is similar
Plenty of s.m. recovered

[discodermolide]

Warm it up somewhat, 35°C.

[orgopete]

This looks like a pretty basic structure and since it is commercially available, I think the chemistry should be reasonably reliable.

I did a Google search and discovered an Aguirre, and others, preparation, http://www.jmcs.org.mx/PDFS/V55/1/09.-%2520Aguirre.pdf. I looked at it and they report a 65% yield, or something like that. However, they did not report any literature on this reaction. It's a commercial product, so it had to have been made before. If that is the reference, that might tell you something.

I also saw other bromination reactions. An interesting reaction was the bromination of 4-hydroxybenzaldehyde. I think this may be a student prep. They do the bromination for less than a minute in methanol and quench with thiosulfate.

Now, you may combine these facts together. Ethanol is often used as a stabilizer in chloroform, Taber used methanol, so the unreported variable is alcohol. The reaction produces HBr, so alcohol can absorb the HBr produced which might also inhibit the reaction.

Me, I'd do a lit search. Look at the chemistry. The preferred products are generally the major products and it can be very difficult to change the preference.

[Babcock_Hall]

orgopete,

I am having trouble with your link.

[darkdevil]

This looks like a pretty basic structure and since it is commercially available, I think the chemistry should be reasonably reliable.

I did a Google search and discovered an Aguirre, and others, preparation, http://www.jmcs.org.mx/PDFS/V55/1/09.-%2520Aguirre.pdf. I looked at it and they report a 65% yield, or something like that. However, they did not report any literature on this reaction. It's a commercial product, so it had to have been made before. If that is the reference, that might tell you something.

I also saw other bromination reactions. An interesting reaction was the bromination of 4-hydroxybenzaldehyde. I think this may be a student prep. They do the bromination for less than a minute in methanol and quench with thiosulfate.

Now, you may combine these facts together. Ethanol is often used as a stabilizer in chloroform, Taber used methanol, so the unreported variable is alcohol. The reaction produces HBr, so alcohol can absorb the HBr produced which might also inhibit the reaction.

Me, I'd do a lit search. Look at the chemistry. The preferred products are generally the major products and it can be very difficult to change the preference.

Thank you! Augirre is the paper Im refering to. I tried 2.5 hours for the reaction today, and making the bromine  and the s.m. chloroform solution more concentrated. I added a dropping funnel and added bromine dropwise under N₂.The yield is much better ~ 25%. but still many s.m. unreacted.

After 2.5 hours, The reaction turned deep green with some yellowish viscous oil left behind. When water was added. The green color changed to orange brown(product is brown in color) with some insoluble dirty pastes at the boundary of water and chloroform layers.

 I can get enough product for the next step, but i am considering if I shall let the reaction to last for longer times next time. 1 hour is not possible to get 65% yield

[billnotgatez]

http://www.jmcs.org.mx/PDFS/V55/1/09.-%20Aguirre.pdf
@Babcock_Hall
This may be the link that @orgopete was trying to post
from
http://www.jmcs.org.mx/OLD/index55-1.php


the link provided earlier had a typo with an extra 25 inside
http://www.jmcs.org.mx/PDFS/V55/1/09.-%2520Aguirre.pdf