Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: ecnerwalc3321 on August 21, 2012, 04:17:38 PM
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I have molecule with a carboxylic acid end (pyrene butyric acid). I was thinking about changing the acid end to a triple bond in order to do click chemistry (azide-alkyne reaction). I was thinking about treating the acid (solid) with excess SOCl2 at room temperature (?) and waiting until all the HCl and SO2 evolution stops. After some time, propargyl alcohol will be added dropwise into reaction chamber. theoretically, the acid chloride will just react with the alcohol and my end product will be formed along with more HCl. However, I was worried that the HCl formed in this process will react with the triple bond and thus render my product less pure. Does anyone have experience with HCl reactions with alkynes? Does the reaction occur readily at room temperature and do you see any shortcomings with my overall synthesis? Thanks.
(Not a chemist by trade-finding out that theory and practice is quite different).
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I have molecule with a carboxylic acid end (pyrene butyric acid). I was thinking about changing the acid end to a triple bond in order to do click chemistry (azide-alkyne reaction). I was thinking about treating the acid (solid) with excess SOCl2 at room temperature (?) and waiting until all the HCl and SO2 evolution stops. After some time, propargyl alcohol will be added dropwise into reaction chamber. theoretically, the acid chloride will just react with the alcohol and my end product will be formed along with more HCl. However, I was worried that the HCl formed in this process will react with the triple bond and thus render my product less pure. Does anyone have experience with HCl reactions with alkynes? Does the reaction occur readily at room temperature and do you see any shortcomings with my overall synthesis? Thanks.
(Not a chemist by trade-finding out that theory and practice is quite different).
A couple of options:
If you are worried by this azeotrope the acid chloride with toluene several times, this should remove any HCl left.
Your acid chloride may well be a solid, in which case you can crystallise it.
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If you use a slight excess of pyridine w/ socl2, you'll mop up any excess HCl.
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@discodermolide,
I would think that my acid chloride would be a solid. However, when I tried carrying out the reaction (~70C, reflux, 2 hours, then distill SOCl2), I'm left with an oily substance. The "oil' doesn't go away even when I vacuum dry it. The butyric acid does dissolve in SOCl2 and chloroform, however.
How would I wash it in toluene if the acid chloride reacts with water? I suppose I could use two organic layers in a sep funnel?
@james_a
So use pyridine as a solvent and run the reaction. After the reaction, do you think I need to distill the pyridine before adding the propargyl alcohol? Or can it be a one-pot synthesis?
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@discodermolide,
I would think that my acid chloride would be a solid. However, when I tried carrying out the reaction (~70C, reflux, 2 hours, then distill SOCl2), I'm left with an oily substance. The "oil' doesn't go away even when I vacuum dry it. The butyric acid does dissolve in SOCl2 and chloroform, however.
How would I wash it in toluene if the acid chloride reacts with water? I suppose I could use two organic layers in a sep funnel?
@james_a
So use pyridine as a solvent and run the reaction. After the reaction, do you think I need to distill the pyridine before adding the propargyl alcohol? Or can it be a one-pot synthesis?
You misunderstood me, sorry.
I make acid chlorides made by dissolving the acid in SOCl2. But you can use toluene as a solvent. Don't put it near water. When the reaction is complete just remove the toluene, add more toluene and re-evaporate. Repeat two or three times, then it should be good to use, and may even crystallise.
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May I ask how you make your acid chlorides? What do "mild" conditions typically entail? Can you just simply dissolve your acid in SOCl2 at room temperature and let the excess SOCl2 evaporate? I've been refluxing mine in a heated water bath and I'm not sure whether this has a big influence on the product (the water is outside the glass, right?). So far, the several IR spectra has been inconclusive due to "oily" product formed.
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May I ask how you make your acid chlorides? What do "mild" conditions typically entail? Can you just simply dissolve your acid in SOCl2 at room temperature and let the excess SOCl2 evaporate? I've been refluxing mine in a heated water bath and I'm not sure whether this has a big influence on the product (the water is outside the glass, right?). So far, the several IR spectra has been inconclusive due to "oily" product formed.
Dissolve or suspend in SOCl2, or toluene, then add SOCl2 heat if required. Monitor by TLC after quench with methanol. Evaporate solvent, then co-evaporate with toluene two or three times to remove volatile material (assuming acid chloride is not volatile). Then use it directly.
Note everything should be dry.
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Isn't the acid chloride pyrenebutyric acid a known compound? You could look up how it was made.
By the way, my preferred way to make an acid chloride is to use dilute my compound in an inert solvent, add thionyl or oxalyl chloride and add a catalytic amount of DMF. DMF becomes converted to an iminoyl chloride which makes the acid chloride and regenerates DMF. The procedure can be found in Fieser and Fieser (if that is still used?).
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Isn't the acid chloride pyrenebutyric acid a known compound? You could look up how it was made.
By the way, my preferred way to make an acid chloride is to use dilute my compound in an inert solvent, add thionyl or oxalyl chloride and add a catalytic amount of DMF. DMF becomes converted to an iminoyl chloride which makes the acid chloride and regenerates DMF. The procedure can be found in Fieser and Fieser (if that is still used?).
My method is a hangover from chemical development. The iminoyl chlorides are unstable and can cause problems on scale with very exothermic decomposition taking place. This is why I don't generally recommend it.
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I'm not surprised if you added DMF to similar mixtures. This sounds like a hang-fire mixture. I did my reactions in the inverse. I added the thionyl chloride or oxalyl chloride. If it didn't start percolating, I would add a little more DMF. I was discovery, so I generally didn't have lethal generations of heat and gas.
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I am pretty confident you will be fine. If I recall correctly, it takes some force to react an alkyne with HCl (large amounts of HCl and high temperatures). If your worried about it, you could always use alternative esterification conditions like create an anhydride from your carboxylic acid then react it with your alcohol. I would say give you reaction a go and see what happens. Thats typically how I find out if things will tolerate reaction conditions :P Only on material that is moderately easy to come by of course ;)
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I am pretty confident you will be fine. …
I agree. I think the main problem has been the preparation of the acid chloride. I have made esters from propargyl alcohol with an acid chloride. This reaction can be carried out without addition to the triple bond.
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Thanks for all the suggestions. I tried all your suggestions along with some different variations in separation, reaction, etc but seem to always come up with the same result as far as what the IR spectra shows. The spectra on top is the pure acid chloride while the one on the bottom is the "acid chloride derivative" which looks suspiciously like water's IR spectra. Two things worries me; that is, the presence of what is perceived to be an alcohol peak at 3400 cm-1 and the unchanging carbonyl peak at ~1700 (should be shifted to ~1800 due to the withdrawing power of Cl).
For this particular sample, I placed ~0.02g PBA in a vial and added 2 ml of SOCl2 along with a couple drops of DMF. The solution was stirred at room temperature overnight in hood. ~15 mL of hexane was then added directly to the solution to form precipitate and the solution was dried in a vacuum oven (no heat). End product looked slightly sticky. IR spectra was taken by forming KBr pellet.
I suppose my question is, "why would a peak appear at 3400?" While I was doing the experiments, I had concerns that I didn't keep the environment dry enough. However, IF the environment still had some water, either from the air or whatever chemicals I used, wouldn't the carboxylic acid be favored? If so, why would I get a different spectra? Shouldn't I get the same spectra as PBA if my samples were exposed to moisture?
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It's sticky probably because the HCl and SO2 are still in there. As I said above:
Dissolve or suspend in SOCl2, or toluene, then add SOCl2 heat if required. Monitor by TLC after quench with methanol. Evaporate solvent, then co-evaporate with toluene two or three times to remove volatile material (assuming acid chloride is not volatile). Then use it directly.
Note everything should be dry.
HCl especially has a nasty tendency to make solids sticky, that's why several toluene evaporations help.
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How would the presence of HCl and SOCl2 explain the IR peaks that I see?
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How would the presence of HCl and SOCl2 explain the IR peaks that I see?
That looks like the acid chloride is no longer an acid chloride. Why did you make a KBr pellet? It exposes everything to moisture. Run an IR in a solvent like toluene, with a toluene blank. Then you could actually follow your reaction by IR.
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i made the KBr pellet because I thought that the product wouldn't be enormously affected by moisture during the brief time that I was making it (why else would people make KBr pellets?). Are the chlorides really that moisture sensitive? As far as solution IRs go, I'm not sure where to get a solution cell; we do have ATR capabilities, though I'm not sure how well that will work since it turns out that pyrene butyric acid/chloride does not dissolve in toluene.
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i made the KBr pellet because I thought that the product wouldn't be enormously affected by moisture during the brief time that I was making it (why else would people make KBr pellets?). Are the chlorides really that moisture sensitive? As far as solution IRs go, I'm not sure where to get a solution cell; we do have ATR capabilities, though I'm not sure how well that will work since it turns out that pyrene butyric acid/chloride does not dissolve in toluene.
How do you know the acid chloride does not dissolve in toluene? Is this literature information?
Some acid chlorides are very sensitive toward moisture.
The acid is insoluble, as it reacts, if the acid chloride is soluble, you will end up with a solution.
If that does not work use neat thionyl chloride.
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I still say it is a literature compound. If all else fails, prepare it the same way someone else has succeeded in preparing it (or just buy, it is commercially available). I see it was reported here, J. Org. Chem., 1984, 49 (1), pp 207–209
DOI: 10.1021/jo00175a055.
By the way, it is an aliphatic acid chloride. They are a lot more reactive than an aryl acid chloride. Acetyl chloride will react virtually explosively with water. It is very reactive. Use that as a guide to how to handle your acid chloride.
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I still say it is a literature compound. If all else fails, prepare it the same way someone else has succeeded in preparing it (or just buy, it is commercially available). I see it was reported here, J. Org. Chem., 1984, 49 (1), pp 207–209
DOI: 10.1021/jo00175a055.
By the way, it is an aliphatic acid chloride. They are a lot more reactive than an aryl acid chloride. Acetyl chloride will react virtually explosively with water. It is very reactive. Use that as a guide to how to handle your acid chloride.
What is worse is that there is an onset time of a couple of seconds or a bit less before the reaction starts. This causes accumulation and then almost a runaway situation. Very nasty.
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i made the KBr pellet because I thought that the product wouldn't be enormously affected by moisture during the brief time that I was making it (why else would people make KBr pellets?). Are the chlorides really that moisture sensitive? As far as solution IRs go, I'm not sure where to get a solution cell; we do have ATR capabilities, though I'm not sure how well that will work since it turns out that pyrene butyric acid/chloride does not dissolve in toluene.
Orgopete says a) it is a known compound and b) it is commercially available. Why not just buy it?
Have a look here, using oxalyl chloride. http://cssp.chemspider.com/Article.aspx?id=206 (http://cssp.chemspider.com/Article.aspx?id=206)
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Thanks to all who replied to this thread. I finally was able to get a reaction to occur as evidenced by the ester peak (~1200 cm-1) in the IR shown below. However, there is now the problem of purification. The solid is dry (not sticky) so I'm pretty sure there is not much of the propargyl alcohol, SOCl2, toluene, hcl, or any liquid remaining. Therefore, the two compounds are pyrenebutyric acid and the ester. Both are solids that don't appear to crystallize (I wasn't able to get them to crystallize. but then again, you can't use recrystallization to separate two solids, can you?). The solids were precipitated using hexane. I've looked through a common list of purification methods but can't pinpoint which one to use as it seems that most are not applicable for the separation of two solids. Does anyone have ideas?
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The ester peak in the IR is very weak. Was the sample dilute? Or did you just not have much material?
You can crystallise solids apart, you just need to find the correct solvent.
If you are sure one of the compounds is the acid you can dissolve the mixture in a solvent and wash with sodium bicarbonate solution. This makes the sodium salt of the acid which should remain in the water, the ester in the organic. Otherwise a maybe more convenient method is flash chromatography on silica-gel.
Here are a couple of links
http://www.youtube.com/watch?v=fF1gXUvyGb4 (http://www.youtube.com/watch?v=fF1gXUvyGb4)
http://en.wikipedia.org/wiki/Column_chromatography (http://en.wikipedia.org/wiki/Column_chromatography)
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Thanks for the suggestion, discodermolide. I just tried using the separatory funnel method and am waiting for the product to dry. We don't have a column (not a chem lab) so chromatography would be a little bit more involved. I did a little reading on the basics of extraction and have a couple questions.
1. If you have two compounds A and B that are soluble in an organic solvent but A is also soluble in water, can you do an extraction of A from the organic to the aqueous phase? If so, what is the driving force that makes this happen? Is it determined by whether the aqueous phase is acidic or basic?
2. If you have C and D (where C is an alkyl halide and D is an alcohol) which are both insoluble in water but soluble in organic, how would you go about extracting C from D?
discodermolide, how were you able to tell that the ester signal is weak? I'm looking at the peak at ~1200 cm-1 and see that it's quite strong. Is this the wrong peak? Thanks.
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First the IR, the ester peak is at 1737 cm-1. It should normally be much stronger. Unless you 1) used very little for the IR, or 2) if it is your reaction mixture then you don't have much ester.
Extractions:
Question 1: This is dependant upon the partition coefficient of A between the solvent and the water. Roughly if you have 100% of A in the organic with a coefficient of 50% then 1 extraction with water will remove 50%, the second extraction 50% 0f the 50%, i.e. 25% and so on. Ultimately with many extractions you will remove A.
Question 2: In this case you probably will not be able to extract them apart with any reasonable success. You could try acetonitrile/heptane, the alcohol will stay in the acetonitrile, the alkyl halide will go into the heptane. This depends very much upon the type of alcohol and alkyl halide you have.
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These results do not seem as expected. Here is a prep and reaction of the acid chloride.
http://www.nanoscalereslett.com/content/pdf/1556-276X-7-296.pdf
Just repeat its preparation and react it the residue with methanol. I think you can skip everything else in this case. The residue should be the ester. Methanol will evaporate, any HCl will evaporate. It should give a reasonable amount of ester. Lets do the simple before we worry about what did or didn't happen in the propargyl alcohol case.
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I think I got it now. First is the IR of your requested compound, orgopete. Second is the IR of my product in question. I feel that you should be able to see what I've made given all the help you have given me. Definitely more convincing evidence that the reaction happened the way it's supposed to?
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That looks like a much better reaction and IR, nice strong ester peak and the triple bond CH at just above 2000cm-1. Congratulations.
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I have been reading some experiments on radiant heat of John Tyndall from 1872. What is common to the experiment noted here is the need to ensure the quality of the experiment. Tyndall goes to length to test for alternate theories. One can find these tests in even the most basic of troubleshooting guides. 1. Plug it in.
I did not think it was a question of the reaction, but the poster had to determine which step was preventing the desired outcome. Is it the reaction, or is is it me? Been there, done that.