[darkdevil]

Hi, I am repeating the below procedures from a paper, but instead of adding the acid chloride dropwise in 30 minutes, I added the acid chloride in 4 separate intervals within 2 minutes. The reaction seemed to go well at first, but after around 4 hours I noticed some side products from TLC instead of the purple and red spot they described in the text.


Since the paper also did not mention how long the reaction took, I kept my reaction to stay reflux overnight. After 1 day, the TLC showed tailing trails on the "red spot" and some other minor side product spots.  I kept go on to separate my product  and obtained a brown material. The material is not my product, and I just wondered if it is so important to add the acid chloride dropwise? and how long should I let my reaction to react?

Thanks!!

[Arkcon]

I suppose it was important to add dropwise, then.  It would be interesting to see what the byproducts are.  We could piece together what happened.  Maybe we can speculate, once we know the structure of the desired product, and if these by-products are more or less polar, what their structures might be.

Thanks for posting, a new student has asked much the same question over here: http://www.chemicalforums.com/index.php?topic=79242.0

[TheUnassuming]

In general its good to assume if the authors specified a certain set of conditions, they are required to get the desired reaction.   I know in my write-ups, I don't say something if it doesn't matter to the reaction.

[darkdevil]

I tried to add the acid chloride in a drop wise manner, but still after 1 day of refluxing the reaction was a mess.
I am not sure if the refluxing time is significant to the reaction process, or the kind of xylene is a factor.
I used m-xylene as the solvent since they also did not mention which kind of xylene was used in their reactions.

[Dan]

I am not sure if the refluxing time is significant to the reaction process.

It probably is. The authors indicate ~50% conversion over the 30 min addition period (or this is how I interpret their report), so it seems unlikely to me that the desired reaction will take all day to complete. The fact that they do not indicate a total reaction time is very poor practice. I am resisting the urge to rant as I have had several problems with atrocious supporting information containing incomplete or blatantly untrue experimental procedures this week.

Anyway, I would monitor this reaction regularly and stop it as soon as the purple spot disappears. Leaving the reaction at reflux for extended periods may result in the major products being those from slower side reactions.

[darkdevil]

Thank you for the reply.
This is a picture of the TLC I just did after 1 day of reaction:


I assume the top "red spot" is my product, and a purple spot below it.
The truth is, after the addition of the acid chloride yesterday (30 minutes dropwise addition), I have a similar TLC to this one except I did not see a blue spot in between the red and pruple spot. Lengthening the reaction time produced more side products only, and I could not observe any disappearance of the purple spot yesterday.

[darkdevil]

All other spots are present after the 30 minutes addition of acid
The blue spot only appeared after 1 day of reflux

[Dan]

That doesn't look fun.

Are you confident of the quality of the acyl chloride?f

You could quench a sample of it with an alcohol and check it by NMR (or even TLC).

Are you using exactly the same reagents as them or applying their procedure to a different compound?

[TheUnassuming]

That doesn't look fun.

Are you confident of the quality of the acyl chloride?f

That looks like a fun mess!  I'll second the double check of your acyl chloride.  Get a good NMR to prove to yourself the reagent is still good and make sure your conditions are good and dry.

I am resisting the urge to rant as I have had several problems with atrocious supporting information containing incomplete or blatantly untrue experimental procedures this week.

Sadly more common than it should be.  What journal?

[darkdevil]

I was just repeating the same procedures done by them
.all are same

[darkdevil]

I assume there is no problem for the reagents used.
May be I shall dry the xylene a bit further?

[TheUnassuming]

I assume there is no problem for the reagents used.
May be I shall dry the xylene a bit further?

If the reaction isn't working as published, probably shouldn't assume that your reagents are good.  This is even true if you recently purchased them. Acyl chlorides aren't known for their stability and I've received more than one compound from suppliers that needed to be re-purified before I could use it.

[darkdevil]

I just checked the proton NMR of my 2-thiopheneacetyl chloride, and there is no problem with it. The material is very clean and pure. And I am sure my indigo is clean as well, since I carried out other reactions on it and there was no problem at all.

[darkdevil]

Now there is only 1 parameter left which is the kind of xylene used in the reaction if the reaction described in their paper is 100% true.

[darkdevil]

In fact I can obtain some product now and I have a near identical NMR from their reference. However, the yield is very low (~8%) while they can get 73% yield... I am not sure why.
Additionally, I filtered my product with a short plug of silica gel (which they did not mention, and if I just filter with a sinter glass funnel, everything will be in the filtrate) and washed with THF. I then used chloroform to wash away my product from the silica gel. I think the silica gel filtration part is very important or else you will get NOTHING if you do an ordinary filtering.
But still the yield is very low, and the product is poorly soluble in chloroform.


Top: my product
Bottom: paper